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Title:
The significant role of amino acids during pregnancy: nutritional support
Authors:
Manta-Vogli, Penelope D.; Schulpis, Kleopatra H.; Dotsikas, Yannis; Loukas, Yannis L.
Abstract:
Background: Pregnancy is characterized by a complexity of metabolic processes that may impact fetal development and infant health outcome. Normal fetal growth and development depend on a continuous supply of nutrients via the placenta. The placenta transports, utilizes, produces, and interconverts amino acids (AAs).Findings: Concentrations of both nonessential and essential AAs in maternal plasma decrease in early pregnancy and persist at low concentrations throughout. The decline is greatest for the glucogenic AAs and AAs of the urea cycle. Additionally, there is a large placental utilization of the branched-chain AAs, some of which are transaminated to alpha ketoacids and contribute to placental ammonia production. Both nonessential and essential AAs regulate key metabolic pathways to improve health, survival, growth, development, lactation, and reproduction of organisms. Some of the nonessential AAs (e.g. glutamine, glutamate, and arginine) play also important roles in regulating gene expression, cell signaling, antioxidant responses, immunity, and neurological function.Conclusions: Nutritional support during pregnancy is of great interest focusing not only to common pregnancies but also to those with low socioeconomic status, vegan-vegetarian groups, and pregnant women with metabolic disorders, the most known maternal phenylketonuria. The latter is of great interest because phenylalanine must be within the recommended range throughout pregnancy in addition to other nutrients such as vitamin B12, folate, etc. Loss of the adherence to this specific diet results in congenital malformations of the fetus. In addition to the routine laboratory test, quantitation of plasma AAs may be necessary throughout pregnancy.
Published:
2020-01
Title:
A Standard Lipid Panel Is Insufficient for the Care of a Patient on a High-Fat, Low-Carbohydrate Ketogenic Diet
Authors:
Norwitz, Nicholas G.; Loh, Vyvyane
Abstract:
High-fat, low-carbohydrate ketogenic diets have recently become popular for weight loss as well as for the treatment of numerous chronic diseases; however, the general medical community still expresses concern regarding the impact of high-fat diets on serum lipids and cardiovascular risk. Herein we report on young man who adopted a ketogenic diet to effectively treat his inflammatory bowel disease. Incidentally, changes in his serum lipids were noted which would be considered adverse by current standards. A more critical analysis of his lipid profile suggests that the changes he experienced may not be dangerous and may, at least with regards to several parameters, represent improvements. This case study demonstrates how the manner in which lipid panels are often reported and reviewed can lead to misleading conclusions and highlights that, at least in the care of those on a ketogenic diet, more nuanced analyses of lipid subfractionations should be conducted in order for physicians to provide optimal care and clinical recommendations.
Published:
2020
Title:
Biological and Technical Challenges in Unraveling the Role of N-Glycans in Immune Receptor Regulation
Authors:
de Haas, Paola; Hendriks, Wiljan J. A. J.; Lefeber, Dirk J.; Cambi, Alessandra
Abstract:
N-glycosylation of membrane receptors is important for a wide variety of cellular processes. In the immune system, loss or alteration of receptor glycosylation can affect pathogen recognition, cell-cell interaction, and activation as well as migration. This is not only due to aberrant folding of the receptor, but also to altered lateral mobility or aggregation capacity. Despite increasing evidence of their biological relevance, glycosylation-dependent mechanisms of receptor regulation are hard to dissect at the molecular level. This is due to the intrinsic complexity of the glycosylation process and high diversity of glycan structures combined with the technical limitations of the current experimental tools. It is still challenging to precisely determine the localization and site-occupancy of glycosylation sites, glycan micro- and macro-heterogeneity at the individual receptor level as well as the biological function and specific interactome of receptor glycoforms. In addition, the tools available to manipulate N-glycans of a specific receptor are limited. Significant progress has however been made thanks to innovative approaches such as glycoproteomics, metabolic engineering, or chemoenzymatic labeling. By discussing examples of immune receptors involved in pathogen recognition, migration, antigen presentation, and cell signaling, this Mini Review will focus on the biological importance of N-glycosylation for receptor functions and highlight the technical challenges for examination and manipulation of receptor N-glycans.
Published:
2020
Title:
Cardioprotective Roles of β-Hydroxybutyrate Against Doxorubicin Induced Cardiotoxicity
Authors:
Liu, Yihai; Wei, Xuan; Wu, Mingyue; Xu, Jiamin; Xu, Biao; Kang, Lina
Abstract:
Background: β-Hydroxybutyrate (BHB) is produced by fatty acid oxidation in the liver under the fasting state and confirmed to play a cardioprotective role in ischemia and hypertensive settings. Doxorubicin (DOX) is an effective chemotherapeutic drug, but limited by serious irreversible cardiotoxicity. However, whether BHB can protect from DOX-induced cardiotoxicity remains unknown. Methods and Results: C57BL/6 mice were intraperitoneally injected with DOX to induce cardiac toxicity and intragastrically administered into BHB for treatment. They were randomly divided into three groups, namely a sham group (Sham), a doxorubicin group (DOX), and a doxorubicin+β-Hydroxybutyrate group (DOX + BHB). Echocardiography and pathological staining were performed to evaluate cardiac function and fibrosis. H9c2 cardiomyocyte was treated with DOX or BHB for in vitro experiments. Cell apoptosis and ROS were determined by flow cytometry. BHB significantly restored DOX-induced cardiac function decline and partially prevented cardiac reverse remodeling, characterized by increased cell size and decreased fibrosis. In vitro, BHB treatment decreased cellular injury and apoptosis. Also, BHB alleviated oxidative stress level and increased mitochondrial membrane potential. Conclusion: Our results suggested that BHB could protected from DOX-induced cardiotoxicity by inhibiting cell apoptosis and oxidative stress and maintaining mitochondrial membrane integrity.
Published:
2020
Title:
Effect of Elevated Ketone Body on Maternal and Infant Outcome of Pregnant Women with Abnormal Glucose Metabolism During Pregnancy
Authors:
Qian, Meichen; Wu, Na; Li, Ling; Yu, Wenshu; Ouyang, Hong; Liu, Xinyan; He, Yujing; Al-Mureish, Abdulrahman
Abstract:
Ketone bodies are one of the products of fat metabolism which can be used as an alternative energy source for the human body in states of glucose deficiency. Normal pregnant women may develop ketosis due to physiological changes during pregnancy, while pregnant women with abnormal glucose metabolism are more likely to develop ketosis due to abnormal insulin secretion. Animal experiments and clinical studies have shown that exposure to high-ketone environments during pregnancy is closely related to adverse maternal and infant outcomes. However, there is no unified conclusion on whether ketone bodies should be routinely monitored during pregnancy. This review summarizes the existing studies on ketone body levels and pregnancy outcomes in the case of abnormal blood glucose during pregnancy, elaborates the current guidelines on the level of ketone bodies, provides the detection and treatment of ketosis in pregnant women with abnormal blood glucose in the clinical practice.
Published:
2020
Title:
Effects of a carbohydrate-restricted diet on hepatic lipid content in adolescents with non-alcoholic fatty liver disease: A pilot, randomized trial
Authors:
Goss, Amy M.; Dowla, Shima; Pendergrass, May; Ashraf, Ambika; Bolding, Mark; Morrison, Shannon; Amerson, Alesha; Soleymani, Taraneh; Gower, Barbara
Abstract:
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has emerged as the most common form of liver disease among adolescents in industrialized countries. While lifestyle intervention remains the hallmark treatment for NAFLD, the most effective dietary strategy to reverse NAFLD in children is unknown. OBJECTIVE: The objective of this study was to determine the effects of a moderately CHO-restricted diet (CRD) vs fat-restricted diet (FRD) in adolescents with NAFLD on reduction in liver fat and insulin resistance. METHODS: Thirty-two children/adolescents (age 9-17) with obesity and NAFLD were randomized to a CRD (50% energy from CHO:protein:fat) or FRD (55:25:20) for 8 weeks. Caloric intakes were calculated to be weight maintaining. Change in hepatic lipid content was measured via magnetic resonance imaging, body composition via dual energy X ray absorptiometry and insulin resistance via a fasting blood sample. RESULTS: Change in hepatic lipid did not differ with diet, but declined significantly (-6.0 ± 4.7%, P < .001 only within the CRD group. We found significantly greater decreases in insulin resistance (HOMA-IR, <.05), abdominal fat mass (P < .01) and body fat mass (P
Published:
2020
Title:
Fructose metabolism as a common evolutionary pathway of survival associated with climate change, food shortage and droughts
Authors:
Johnson, R. J.; Stenvinkel, P.; Andrews, P.; Sánchez‐Lozada, L. G.; Nakagawa, T.; Gaucher, E.; Andres‐Hernando, A.; Rodriguez‐Iturbe, B.; Jimenez, C. R.; Garcia, G.; Kang, D.-H.; Tolan, D. R.; Lanaspa, M. A.
Abstract:
Mass extinctions occur frequently in natural history. While studies of animals that became extinct can be informative, it is the survivors that provide clues for mechanisms of adaptation when conditions are adverse. Here, we describe a survival pathway used by many species as a means for providing adequate fuel and water, while also providing protection from a decrease in oxygen availability. Fructose, whether supplied in the diet (primarily fruits and honey), or endogenously (via activation of the polyol pathway), preferentially shifts the organism towards the storing of fuel (fat, glycogen) that can be used to provide energy and water at a later date. Fructose causes sodium retention and raises blood pressure and likely helped survival in the setting of dehydration or salt deprivation. By shifting energy production from the mitochondria to glycolysis, fructose reduced oxygen demands to aid survival in situations where oxygen availability is low. The actions of fructose are driven in part by vasopressin and the generation of uric acid. Twice in history, mutations occurred during periods of mass extinction that enhanced the activity of fructose to generate fat, with the first being a mutation in vitamin C metabolism during the Cretaceous–Paleogene extinction (65 million years ago) and the second being a mutation in uricase that occurred during the Middle Miocene disruption (12–14 million years ago). Today, the excessive intake of fructose due to the availability of refined sugar and high-fructose corn syrup is driving ‘burden of life style’ diseases, including obesity, diabetes and high blood pressure.
Published:
2020
Title:
Gallic Acid Ameliorated Impaired Lipid Homeostasis in a Mouse Model of High-Fat Diet—and Streptozotocin-Induced NAFLD and Diabetes through Improvement of β-oxidation and Ketogenesis
Authors:
Chao, Jung; Cheng, Hao-Yuan; Chang, Ming-Ling; Huang, Shyh-Shyun; Liao, Jiunn-Wang; Cheng, Yung-Chi; Peng, Wen-Huang; Pao, Li-Heng
Abstract:
Gallic acid (GA) is a simple polyphenol found in food and traditional Chinese medicine. Here, we determined the effects of GA administration in a combined mouse model of high-fat diet (HFD)-induced obesity and low-dose streptozotocin (STZ)-induced hyperglycemia, ...
Published:
2020
Title:
Insulin Resistance at the Crossroad of Alzheimer Disease Pathology: A Review
Authors:
Berlanga-Acosta, Jorge; Guillén-Nieto, Gerardo; Rodríguez-Rodríguez, Nadia; Bringas-Vega, Maria Luisa; García-Del-Barco-Herrera, Diana; Berlanga-Saez, Jorge O.; García-Ojalvo, Ariana; Valdés-Sosa, Mitchell Joseph; Valdés-Sosa, Pedro A.
Abstract:
Insulin plays a major neuroprotective and trophic function for cerebral cell population, thus countering apoptosis, beta-amyloid toxicity, and oxidative stress; favoring neuronal survival; and enhancing memory and learning processes. Insulin resistance and impaired cerebral glucose metabolism are invariantly reported in Alzheimer's disease (AD) and other neurodegenerative processes. AD is a fatal neurodegenerative disorder in which progressive glucose hypometabolism parallels to cognitive impairment. Although AD may appear and progress in virtue of multifactorial nosogenic ingredients, multiple interperpetuative and interconnected vicious circles appear to drive disease pathophysiology. The disease is primarily a metabolic/energetic disorder in which amyloid accumulation may appear as a by-product of more proximal events, especially in the late-onset form. As a bridge between AD and type 2 diabetes, activation of c-Jun N-terminal kinase (JNK) pathway with the ensued serine phosphorylation of the insulin response substrate (IRS)-1/2 may be at the crossroads of insulin resistance and its subsequent dysmetabolic consequences. Central insulin axis bankruptcy translates in neuronal vulnerability and demise. As a link in the chain of pathogenic vicious circles, mitochondrial dysfunction, oxidative stress, and peripheral/central immune-inflammation are increasingly advocated as major pathology drivers. Pharmacological interventions addressed to preserve insulin axis physiology, mitochondrial biogenesis-integral functionality, and mitophagy of diseased organelles may attenuate the adjacent spillover of free radicals that further perpetuate mitochondrial damages and catalyze inflammation. Central and/or peripheral inflammation may account for a local flood of proinflammatory cytokines that along with astrogliosis amplify insulin resistance, mitochondrial dysfunction, and oxidative stress. All these elements are endogenous stressor, pro-senescent factors that contribute to JNK activation. Taken together, these evidences incite to identify novel multi-mechanistic approaches to succeed in ameliorating this pandemic affliction.
Published:
2020
Title:
Intestinal Transcriptome Analysis Reveals Soy Derivative-Linked Changes in Atlantic Salmon
Authors:
Kiron, Viswanath; Park, Youngjin; Siriyappagouder, Prabhugouda; Dahle, Dalia; Vasanth, Ghana K.; Dias, Jorge; Fernandes, Jorge M. O.; Sørensen, Mette; Trichet, Viviane Verlhac
Abstract:
Intestinal inflammation in farmed fish is a non-infectious disease that deserves attention because it is a major issue linked to carnivorous fishes. The current norm is to formulate feeds based on plant-derived substances, and the ingredients that have antinutritional factors are known to cause intestinal inflammation in fishes such as Atlantic salmon. Hence, we studied inflammatory responses in the distal intestine of Atlantic salmon that received a feed rich in soybean derivatives, employing histology, transcriptomic and flow cytometry techniques. The fish fed on soy products had altered intestinal morphology as well as upregulated inflammation-associated genes and aberrated ion transport-linked genes. The enriched pathways for the upregulated genes were among others taurine and hypotaurine metabolism, drug metabolism—cytochrome P450 and steroid biosynthesis. The enriched gene ontology terms belonged to transmembrane transporter- and channel-activities. Furthermore, soybean products altered the immune cell counts; lymphocyte-like cell populations were significantly higher in the whole blood of fish fed soy products than those of control fish. Interestingly, the transcriptome of the head kidney did not reveal any differential gene expression, unlike the observations in the distal intestine. The present study demonstrated that soybean derivatives could evoke marked changes in intestinal transport mechanisms and metabolic pathways, and these responses are likely to have a significant impact on the intestine of Atlantic salmon. Hence, soybean-induced enteritis in Atlantic salmon is an ideal model to investigate the inflammatory responses at the cellular and molecular levels.
Published:
2020
Title:
Ketones for Post-exercise Recovery: Potential Applications and Mechanisms
Authors:
Mansor, Latt Shahril; Woo, Geoffrey Hubert
Abstract:
Ketogenic diet has been introduced in therapeutic areas for more than a century, but the role of ketones in exercise performance has only been explored in the past decade. One of the main reasons that allows the investigation of the role of ketones in exercise performance is the emergence of exogenous ketones, allowing athletes to achieve the state of ketosis acutely, and independent of their metabolic states. While there are mixed results showing either exogenous ketones improve exercise performance or no effect, the mechanisms of action are still being heavily researched. Moreover, these early data from exercise physiology studies suggested that exogenous ketones may play a more prominent role in post-exercise recovery, leading to a more pronounced cumulative impact over subsequent exercise performance. This review will look at existing evidence on the role of ketones in recovery and attempt to identify the current best practices and potential mechanisms that drive improved recovery.
Published:
2020
Title:
Livestock in Evolving Foodscapes and Thoughtscapes
Authors:
Leroy, Frédéric; Hite, Adele H.; Gregorini, Pablo
Abstract:
Humanity’s main societal and epistemic transitions also mirror changes in its approach to the food system. This particularly holds true for human-animal interactions and the consumption of animal source foods (red meat especially, and to a lesser degree dairy, eggs, poultry, and fish). Hunter-gathering has been by far the longest prevailing form of human sustenance, followed by a diffuse transition to crop agriculture and animal husbandry. This transition eventually stabilized as a state-controlled model based on the domestication of plants, animals, and humans. A shift to a post-domestic paradigm was initiated during the 19th century in the urbanizing populations of the Anglosphere, which was characterized by the rise of agri-food corporations, an increased meat supply, and a disconnect of most of its population from the food chain. While this has improved undernutrition, various global threats have been emerging in parallel. The latter include, among others, a public health crisis, climate change, pandemics, and societal class anxieties. This state of affairs is an unstable one, setting the conditions of possibility for a new episteme that may evolve beyond mere adjustments within the business-as-usual model. At least two disruptive scenarios have been described in current food discourses, both by scientists and mass media. Brought to its extreme, the first scenario relates to the radical abolishment of livestock, rewilding, a ‘plants-only’ diet, and vegan ideology. A second option consists of a holistic approach to animal husbandry, involving more harmonic and richer types of human-animal-land interactions. We argue that - instead of reactive pleas for less or none - future thoughtscapes should emphasize ‘more of the better’.
Published:
2020
Title:
Metabolic effects of a prolonged, very-high-dose dietary fructose challenge in healthy subjects
Authors:
Smajis, Sabina; Gajdošík, Martin; Pfleger, Lorenz; Traussnigg, Stefan; Kienbacher, Christian; Halilbasic, Emina; Ranzenberger-Haider, Tamara; Stangl, Anna; Beiglböck, Hannes; Wolf, Peter; Lamp, Tanja; Hofer, Astrid; Gastaldelli, Amalia; Barbieri, Chiara; Luger, Anton; Trattnig, Siegfried; Kautzky-Willer, Alexandra; Krššák, Martin; Trauner, Michael; Krebs, Michael
Abstract:
BACKGROUND: Increased fructose intake has been associated with metabolic consequences such as impaired hepatic lipid metabolism and development of nonalcoholic fatty liver disease (NAFLD). OBJECTIVES: The aim of this study was to investigate the role of fructose in glucose and lipid metabolism in the liver, heart, skeletal muscle, and adipose tissue. METHODS: Ten healthy subjects (age: 28 ± 19 y; BMI: 22.2 ± 0.7 kg/m2) underwent comprehensive metabolic phenotyping prior to and 8 wk following a high-fructose diet (150 g daily). Eleven patients with NAFLD (age: 39.4 ± 3.95 y; BMI: 28.4 ± 1.25) were characterized as "positive controls." Insulin sensitivity was analyzed by a 2-step hyperinsulinemic euglycemic clamp, and postprandial interorgan crosstalk of lipid and glucose metabolism was evaluated, by determining postprandial hepatic and intra-myocellular lipid and glycogen accumulation, employing magnetic resonance spectroscopy (MRS) at 7 T. Myocardial lipid content and myocardial function were assessed by 1H MRS imaging and MRI at 3 T. RESULTS: High fructose intake resulted in lower intake of other dietary sugars and did not increase total daily energy intake. Ectopic lipid deposition and postprandial glycogen storage in the liver and skeletal muscle were not altered. Postprandial changes in hepatic lipids were measured [Δhepatocellular lipid (HCL)_healthy_baseline: -15.9 ± 10.7 compared with ± ΔHCL_healthy_follow-up: -6.9 ± 4.6; P = 0.17] and hepatic glycogen (Δglycogen_baseline: 64.4 ± 14.1 compared with Δglycogen_follow-up: 51.1 ± 9.8; P = 0.42). Myocardial function and myocardial mass remained stable. As expected, impaired hepatic glycogen storage and increased ectopic lipid storage in the liver and skeletal muscle were observed in insulin-resistant patients with NAFLD. CONCLUSIONS: Ingestion of a high dose of fructose for 8 wk was not associated with relevant metabolic consequences in the presence of a stable energy intake, slightly lower body weight, and potentially incomplete absorption of the orally administered fructose load. This indicated that young, metabolically healthy subjects can at least temporarily compensate for increased fructose intake. This trial was registered at www.clinicaltrials.gov as NCT02075164.
Published:
2020
Title:
Monocytes and the Host Response to Fungal Pathogens
Authors:
Heung, Lena J.
Abstract:
Monocytes and their derivatives, including macrophages and dendritic cells, play diverse roles in the response to fungal pathogens. Sensing of fungi by monocytes triggers signaling pathways that mediate direct effects like phagocytosis and cytokine production. Monocytes can also present fungal antigens to elicit adaptive immune responses. These monocyte-mediated pathways may be either beneficial or harmful to the host. In some instances, fungi have developed mechanisms to evade the consequences of monocyte activation and subvert these cells to promote disease. Thus, monocytes are critically involved in mediating the outcomes of these often highly fatal infections. This review will highlight the roles of monocytes in the immune response to some of the major fungi that cause human disease, including Aspergillus, Cryptococcus, Candida, Histoplasma, Blastomyces, and Coccidioides, and discuss potential strategies to manipulate monocyte responses in order to enhance anti-fungal immunity in susceptible hosts.
Published:
2020
Title:
National Diabetes Statistics Report 2020
Authors:
Center for Disease Control and Prevention
Abstract:
The National Diabetes Statistics Report provides up-to-date scientific data on diabetes and its burden in the United States.
Published:
2020
Title:
Ophthalmic findings in 10 captive, anesthetized chimpanzees (Pan troglodytes)
Authors:
Sigmund, Alex B.; Cushing, Andrew C.; Hendrix, Diane V. H.
Abstract:
Objectives To document ophthalmic findings, Schirmer's tear test I (STT), and intraocular pressure (IOP) values for anesthetized chimpanzees (Pan troglodytes). Animals Studied Ten captive chimpanzees from Zoo Knoxville and Chattanooga Zoo. Procedures Ten chimpanzees were anesthetized for annual physical examinations, blood collection, and ophthalmic examination. Each was anesthetized with intramuscular (IM) injections of dexmedetomidine, midazolam, and ketamine. Ophthalmic findings and STT and IOP values in addition to general health information were recorded for each chimpanzee. Pupillary diameter was measured after topical tropicamide administration. A Shapiro-Wilk test of normality was done for age, weight, STT values, IOP values, and pupil size. Results Ages ranged from 11 to 42 years. Weight range was 40.9-83.6 kg. The mean STT was 13.4 ± 5.3 mm/min. The mean IOP was 14 ± 4.2 mm Hg. Seven of the 10 chimpanzees were considered geriatric, and each had perilimbal lipid deposits. Sedative-associated miosis was successfully counteracted with a regimen of repeated applications of tropicamide, enabling complete fundic examination. Conclusions A complete ophthalmic examination can be done on anesthetized chimpanzees with the protocol used in this study.
Published:
2020
Title:
Plant-Based Meats, Human Health, and Climate Change
Authors:
van Vliet, Stephan; Kronberg, Scott L.; Provenza, Frederick D.
Abstract:
There is wide scale concern about the effects of red meat on human health and climate change. Plant-based meat alternatives, designed to mimic the sensory experience and nutritional value of red meat, have recently been introduced into consumer markets. Plant-based meats are marketed under the premise of environmental and human health benefits and are aimed appeal to a broad consumer base. Meat production is critiqued for its overuse of water supplies, landscape degradation, and greenhouse gas emission, and depending on production practices, environmental footprints may be lower with plant-based meat alternatives. Life-cycle analyses suggest that the novel plant-based meat alternatives have an environmental footprint that may be lower than beef finished in feedlots, but higher than beef raised on well-managed pastures. In this review, we discuss the nutritional and ecological impacts of eating plant-based meat alternatives vs. animal meats. Most humans fall on a spectrum of omnivory: they satisfy some nutrient requirements better from plant foods, while needs for other nutrients are met more readily from animal foods. Animal foods also facilitate the uptake of several plant-derived nutrients (zinc and iron), while plant nutrients can offer protection against potentially harmful compounds in cooked meat. Thus, plant and animal foods operate in symbiotic ways to improve human health. The mimicking of animal foods using isolated plant proteins, fats, vitamins, and minerals likely underestimates the true nutritional complexity of whole foods in their natural state, which contain hundreds to thousands of nutrients that impact human health. Novel plant-based meat alternatives should arguably be treated as meat alternatives in terms of sensory experience, but not as true meat replacements in terms of nutrition. If consumers wish to replace some of their meat with plant-based alternatives in the diet (a “flexitarian approach”) this is unlikely to negatively impact their overall nutrient status, but this also depends on what other foods are in their diet and the life stage of the individual.
Published:
2020
Title:
Protocol for the Use of the Ketogenic Diet in Preclinical and Clinical Practice
Authors:
Kraeuter, Ann-Katrin; Guest, Paul C.; Sarnyai, Zoltán
Abstract:
Many age-related diseases are associated with metabolic abnormalities, and dietary interventions may have some benefit in alleviating symptoms or in delaying disease onset. Here, we review the commonly used best practices involved in applications of the ketogenic diet to facilitate its translation into clinical use. The findings reveal that better education of physicians is essential for applying the optimum diet and monitoring its effects in clinical practice. In addition, investigators should carefully consider potential confounding factors prior to commencing studies involving a ketogenic diet. Most importantly, current studies should improve their reporting on ketone levels as well as on the intake of both macro- and micronutrients. Finally, more detailed studies on the mechanism of action are necessary to help identify potential biomarkers for response prediction and monitoring, and to uncover new drug targets to aid the development of novel treatments.
Published:
2020
Title:
Revisiting the Global Overfat Pandemic
Authors:
Maffetone, Philip B.; Laursen, Paul B.
Abstract:
The previously described overfat pandemic, estimated to be 62-76% worldwide, is comprised of individuals with excess body fat sufficient to impair health. The overfat condition is common in those who are overweight and obese, and can also occur in significant numbers of normal-weight non-obese individuals. Being overfat increases the risk for a wide spectrum of common cardiovascular and metabolic (cardiometabolic) abnormalities, chronic diseases and physical impairment. In some ethnicities, up to 40% or more of those who are normal-weight and non-obese may be overfat, a figure twice that used in the original global overfat estimates. In addition to the rates of overfat outpacing overweight and obesity, non-White populations outnumber Whites 6:1, with the recently estimated overfat prevalence being low when considering ethnicities such as Asians, Chinese, Africans and Latin Americans, including these individuals living among predominantly White populations. An awareness of the extent of the overfat pandemic is important because excess body fat can precede cardiometabolic risk factors, chronic diseases, and physical disabilities, and can reduce quality of life and increase healthcare expenditure. The purpose of this Perspective is to demonstrate that the global overfat prevalence of 62-76% may be considerably underestimated.
Published:
2020
Title:
Symposium 'understanding and managing satiety: processes and opportunities'
Authors:
Mandalari, Giuseppina
Abstract:
This brief report summarises a framework for understanding satiety presented at the 13th European Nutrition Conference, FENS 2019 - Malnutrition in an Obese World: European Perspectives. Aspects of satiety phenotyping and role of food hedonics in satiation are considered in the context of appetite control and obesity. Almonds are evaluated for their unique composition and structure which affect their behaviour in the human gastrointestinal tract. Their role in appetite control and management of satiety has been explored.
Published:
2020
Title:
The Effect of Atopic Dermatitis and Diet on the Skin Transcriptome in Staffordshire Bull Terriers
Authors:
Anturaniemi, Johanna; Zaldívar-López, Sara; Savelkoul, Huub F. J.; Elo, Kari; Hielm-Björkman, Anna
Abstract:
Canine atopic dermatitis (CAD) has a hereditary basis that is modified by interactions with the environment, including diet. Differentially expressed genes in non-lesional skin, determined by RNA sequencing before and after a dietary intervention, were compared between dogs with naturally occurring CAD (n=4) and healthy dogs (n=4). The dogs were fed either a common commercial heat-processed high carbohydrate food (kibble diet) (n=4), or a non-processed high fat food (raw meat-based diet) (n=4). At the end of the diet intervention, 149 differentially expressed transcripts were found between the atopic and healthy dogs. The main canonical pathways altered by the dysregulation of these genes were angiopoietin signaling, epidermal growth factor signaling, activation of angiogenesis, and alterations in keratinocyte proliferation and lipid metabolism. On the other hand, 33 differently expressed transcripts were found between the two diet groups, of which 8 encode genes that are annotated in the current version of the dog genome: immunoglobulin heavy constant mu (IGHM), immunoglobulin lambda-like polypeptide 5 (IGLL5), B-cell antigen receptor complex-associated protein beta chain (CD79B), polymeric immunoglobulin receptor (PIGR), cystathione β-synthase (CBS), argininosuccinate synthase 1 (ASS1), secretory leukocyte peptidase inhibitor (SLPI), and mitochondrial ribosome recycling factor (MRRF). All genes were upregulated in the raw diet group. In conclusion the findings of this study suggest alterations in lipid and keratinocyte metabolism as well as angiogenesis in the skin of atopic dogs. Additionally, a possible enhancement of innate immunity and decrease in oxidative stress was seen in raw food fed dogs, which could have an important role in preventing hypersensitivities and disturbed immunity at young age.
Published:
2020
Title:
The Integration of Farmers and Nomads: Archaeological Evidence for the Human Subsistence Strategy in Northwestern China during the Han Dynasty
Authors:
Li, Xin; Lu, Minxia; Cui, Yifu; Liu, Ruiliang; Ma, Minmin
Abstract:
The integration of farmers and nomads in northwestern China during the Han Dynasty (206 BCE 220 CE) provides a crucial opportunity to reconstruct the material exchanges, formation and development of the Silk Road in antiquity. The subsistence strategy is arguably an effective proxy for the integration of various groups of people (e.g. farmers and nomads). In this paper, we have reported new stable isotope data from the Huangwan tombs dated to the Han dynasty in middle Gansu, which was the key juncture between the Han and Xiongnu empire, in order to fill the gap and further understand the substance strategies employed by the local people. According to the results of plant remains and stable isotopic data, millet farming, the typical agricultural activities for the Han Chinese in the Central Plains, was also the primary lifestyle for the Huangwan people in the mid Gansu. More importantly, this shows fundamentally remarkable difference from the agricultural practices in the Bronze Age Gansu Corridor, which were based on a variety of crops, including wheat, barley and millet. This major shift in the subsistence production at Huangwan can be correlated to a wider historical background in which the Han empire showed increasing political and military presence in the Gansu Corridor, indicating that local indigenous nomads followed the lifestyle of Han Chinese (e.g., millet farming), and/or the Han immigrates maintained millet farming.
Published:
2020
Title:
The Internal, External and Extended Microbiomes of Hominins
Authors:
Dunn, Robert R.; Amato, Katherine R.; Archie, Elizabeth A.; Arandjelovic, Mimi; Crittenden, Alyssa N.; Nichols, Lauren M.
Abstract:
The social structure of primates has recently been shown to influence the composition of their microbiomes. What is less clear is how the microbiome composition of primates might influence their social behavior, either in general or with particular reference to hominins. Here we use a comparative approach to understand how microbiomes of hominins have, or might have, changed since the last common ancestor of chimpanzees and humans, roughly six million years ago. We focus on microbiomes associated with social evolution, namely those hosted or influenced by stomachs, intestines, armpits, and food fermentation. In doing so, we highlight the potential influence of microbiomes in hominin evolution while also offering a series of hypotheses and questions with regard to evolution of human stomach acidity, the factors structuring gut microbiomes, the functional consequences of changes in armpit ecology, and whether Homo erectus was engaged in fermentation. We conclude by briefly considering the possibility that hominin social behavior was influenced by prosocial microbes whose fitness was favored by social interactions among individual hominins.
Published:
2020
Title:
The effect of a ketogenic diet and synergy with rapamycin in a mouse model of breast cancer
Authors:
Zou, Yiyu; Fineberg, Susan; Pearlman, Alexander; Feinman, Richard D.; Fine, Eugene J.
Abstract:
BACKGROUND: The effects of diet in cancer, in general, and breast cancer in particular, are not well understood. Insulin inhibition in ketogenic, high fat diets, modulate downstream signaling molecules and are postulated to have therapeutic benefits. Obesity and diabetes have been associated with higher incidence of breast cancer. Addition of anti-cancer drugs together with diet is also not well studied. METHODS: Two diets, one ketogenic, the other standard mouse chow, were tested in a spontaneous breast cancer model in 34 mice. Subgroups of 3-9 mice were assigned, in which the diet were implemented either with or without added rapamycin, an mTOR inhibitor and potential anti-cancer drug. RESULTS: Blood glucose and insulin concentrations in mice ingesting the ketogenic diet (KD) were significantly lower, whereas beta hydroxybutyrate (BHB) levels were significantly higher, respectively, than in mice on the standard diet (SD). Growth of primary breast tumors and lung metastases were inhibited, and lifespans were longer in the KD mice compared to mice on the SD (p
Published:
2020
Title:
Treating binge eating and food addiction symptoms with low-carbohydrate Ketogenic diets: a case series
Authors:
Carmen, Matthew; Safer, Debra Lynn; Saslow, Laura R.; Kalayjian, Tro; Mason, Ashley E.; Westman, Eric C.; Sethi Dalai, Shebani
Abstract:
Background: Many patients with obesity and comorbid binge eating symptoms present with the desire to lose weight. Although some studies suggest that dietary restriction can exacerbate binge eating, others show dietary restriction is associated with significant reductions in binge eating. The effect of a particular type of dieting on binge eating, the ketogenic diet (a high fat, moderate protein, very low carbohydrate diet), is not known. Case presentations: We report on the feasibility of a low-carbohydrate ketogenic diet initiated by three patients (age 54, 34, and 63) with obesity (average BMI 43.5 kg/m2) with comorbid binge eating and food addiction symptoms. All patients tolerated following the ketogenic diet (macronutrient proportion 10% carbohydrate, 30% protein, and 60% fat; at least 5040 kJ) for the prescribed period (e.g., 6-7 months) and none reported any major adverse effects. Patients reported significant reductions in binge eating episodes and food addiction symptoms including cravings and lack of control as measured by the Binge-Eating Scale, Yale Food Addiction Scale, or Yale-Brown Obsessive-Compulsive Scale modified for Binge Eating, depending on the case. Additionally, the patients lost a range of 10-24% of their body weight. Participants reported maintenance of treatment gains (with respect to weight, binge eating, and food addiction symptoms) to date of up to 9-17 months after initiation and continued adherence to diet. Conclusions: Although the absence of control cases precludes conclusions regarding the specific role of ketogenic diets versus other forms of dietary restriction, this is the first report to demonstrate the feasibility of prescribing a ketogenic diet for patients with obesity who report binge eating and food addiction symptoms. Further research should seek to reproduce the observed effects in controlled trials as well as to explore potential etiologies.
Published:
2020
Title:
Wood and meat as complementary sources of sodium for Kanyawara chimpanzees (Pan troglodytes)
Authors:
Venable, Emily M.; Machanda, Zarin; Hagberg, Lindsey; Lucore, Jordan; Otali, Emily; Rothman, Jessica M.; Uwimbabazi, Moreen; Wrangham, Richard
Abstract:
Objectives Sodium, a vital micronutrient that is often in scarce supply for tropical herbivores, is sometimes found at high concentration in decaying wood. We tested two hypotheses for chimpanzees: first, that wood-eating facilitates acquisition of sodium; second, that wood-eating occurs in response to the low availability of sodium from other dietary sources. Materials and Methods We studied the behavior of more than 50 chimpanzees of all age-sex classes in the Kanyawara community of Kibale National Park, Uganda. We quantified the sodium content of dietary items, including wood samples from tree species that chimpanzees consumed or did not consume. To assess variation in sodium intake, we used 7 years of data on time spent feeding on plant foods, 18 months of data on rates of food intake by adult females, and 20 years of data on meat-eating. Results Major dietary sources of sodium were wood, fruits and meat. Chimpanzees consumed wood primarily from decaying trees of Neoboutonia macrocalyx (Euphorbiaceae), which had substantially higher sodium content than all other dietary items tested. Wood-eating was negatively correlated with fruit-eating. Females ate wood more often than males, while males had a greater probability of consuming meat at predation events. Discussion We propose that females ate wood more often than males because females had reduced access to meat, their preferred source of sodium. This hypothesis suggests that the need for sodium is a motivating reason for chimpanzees to consume both meat and wood.
Published:
2020
Title:
Changes in Food Cravings and Eating Behavior after a Dietary Carbohydrate Restriction Intervention Trial
Authors:
Anguah, Katherene O.-B.; Syed-Abdul, Majid M.; Hu, Qiong; Jacome-Sosa, Miriam; Heimowitz, Colette; Cox, Vicki; Parks, Elizabeth J.
Abstract:
\textlessp\textgreaterCompared to low-fat diets, low-carbohydrate (CHO) diets cause weight loss (WL) over a faster time frame; however, it is unknown how changes in food cravings and eating behavior contribute to this more rapid WL in the early phases of dieting. We hypothesized that reductions in food cravings and improved eating behaviors would be evident even after a relatively short (4-week) duration of CHO-restriction, and that these changes would be associated with WL. Adult participants (n = 19, 53% males, mean ± SD: BMI = 34.1 ± 0.8 kg/m2; age 40.6 ± 1.9 years) consumed a CHO-restricted diet (14% CHO, 58% fat, 28% protein) for 4 weeks. Before and after the intervention, specific and total cravings were measured with the Food Craving Inventory (FCI) and eating behaviors assessed with the Three-Factor Eating questionnaire. Food cravings were significantly reduced at week 4, while women had significantly greater reductions in sweet cravings than men. Dietary restraint was significantly increased by 102%, while disinhibiton and hunger scores were reduced (17% and 22%, respectively, p \textless 0.05). Changes in cravings were unrelated to changes in body weight except for the change in high-fat cravings where those who lost the most weight experienced the least reductions in fat cravings (r = −0.458, p = 0.049). Changes in dietary restraint were inversely related to several FCI subscales. A short-term, low-CHO diet was effective in reducing food cravings. These data suggest that in subjects that have successfully lost weight on a low-CHO diet, those who craved high-fat foods at the onset were able to satisfy their cravings—potentially due to the high-fat nature of this restricted diet.\textless/p\textgreater
Published:
2019-12
Title:
Chronic inflammation in the etiology of disease across the life span
Authors:
Furman, David; Campisi, Judith; Verdin, Eric; Carrera-Bastos, Pedro; Targ, Sasha; Franceschi, Claudio; Ferrucci, Luigi; Gilroy, Derek W.; Fasano, Alessio; Miller, Gary W.; Miller, Andrew H.; Mantovani, Alberto; Weyand, Cornelia M.; Barzilai, Nir; Goronzy, Jorg J.; Rando, Thomas A.; Effros, Rita B.; Lucia, Alejandro; Kleinstreuer, Nicole; Slavich, George M.
Abstract:
Published:
2019-12
Title:
Comparison of human monocyte derived macrophages and THP1-like macrophages as in vitro models for M. tuberculosis infection
Authors:
Madhvi, Abhilasha; Mishra, Hridesh; Leisching, Gr; Mahlobo, Pz; Baker, B
Abstract:
Macrophages are the preferential cell types to study various aspects of mycobacterial infection. Commonly used infection models for in-vitro studies are primary macrophages such as human monocyte derived macrophages (hMDMs) and macrophage like cell lines (THP-1). It is not clear if commercially available THP-1 cells can be used as hMDMs alternative for in-vitro M.tb infection experiments. We conducted a detailed investigation of the hMDM and THP-1 response to mycobacterial infection on a comparative basis and assess the most crucial aspects of infection which are most commonly studied. We assessed mycobacterial uptake and intracellular growth over time of a pathogenic drug-resistant and drug-susceptible M.tb strains (R179 and H37Rv) through colony forming units (CFUs). Both strains depicted similar uptake and intracellular growth in hMDMs and THP-1 macrophages over time (R179, p = 0.954) (H37Rv, p = 0.922). Cytotoxicity assays revealed a consistent viability up to day 16 post-infection across the strains in both THP-1 and hMDMs (R179, p = 0.271) (H37Rv, p = 0.068). Interestingly, both cell lines showed similar mycobacterial uptake and cellular viability in both susceptible as well as resistant M.tb strains. Cytokine/chemokine mRNA analysis through qPCR found no difference between cell types. Further, cytokine secretion measured through Luminex revealed no difference across the strains. Also, cytokine secretion analysis showed no difference in both cell lines across strains. In conclusion, our study shows that THP-1 and hMDMs bacterial uptake, viability and host response to drug-susceptible and drug-resistant mycobacterial infections are similar. Therefore, present study demonstrate that THP-1 cells are suitable substitutes for hMDMs for in-vitro M.tb infection experiments.
Published:
2019-12
Title:
Genetic risk for schizophrenia and developmental delay is associated with shape and microstructure of midline white-matter structures
Authors:
Drakesmith, Mark; Parker, Greg D.; Smith, Jacqueline; Linden, Stefanie C.; Rees, Elliott; Williams, Nigel; Owen, Michael J.; van den Bree, Marianne; Hall, Jeremy; Jones, Derek K.; Linden, David E. J.
Abstract:
Published:
2019-12
Title:
Increased 5-HT2C receptor editing predisposes to PTSD-like behaviors and alters BDNF and cytokines signaling
Authors:
Règue, Mathilde; Poilbout, Corinne; Martin, Vincent; Franc, Bernard; Lanfumey, Laurence; Mongeau, Raymond
Abstract:
Post-traumatic stress disorder (PTSD) is a trauma- and stress-related disorder with dysregulated fear responses and neurobiological impairments, notably at neurotrophic and inflammation levels. Understanding the mechanisms underlying this disease is crucial to develop PTSD models that meet behavioral and neurobiological validity criteria as well as innovative therapeutic approaches. Serotonin 2C receptors (5-HT2CR) are known for their important role in anxiety, and mice having only the fully edited VGV isoform of 5-HT2CR, which thereby overexpressed brain 5-HT2CR, are of special interest to study PTSD predisposition. Innate and conditioned fear-related behaviors were assessed in VGV and wild-type mice. mRNA expression of brain-derived neurotrophic factor (BDNF), tissue-plasminogen activator (tPA), and pro-inflammatory cytokines (IL-6, IL-1β, and calcineurin) were measured by qRT-PCR. The effect of acute and chronic paroxetine was evaluated on both behavior and gene expression. VGV mice displayed greater fear expression, extensive fear extinction deficits, and fear generalization. Paroxetine restored fear extinction in VGV mice when administered acutely and decreased innate fear and fear generalization when administered chronically. In parallel, Bdnf, tPA, and pro-inflammatory cytokines mRNA levels were dysregulated in VGV mice. Bdnf and tPA mRNA expression was decreased in the hippocampus but increased in the amygdala, and chronic paroxetine normalized Bdnf mRNA levels both in the amygdala and the hippocampus. Amygdalar calcineurin mRNA level in VGV mice was also normalized by chronic paroxetine. VGV-transgenic mice displayed behavioral and neurobiological features that could be accessory to the investigation of PTSD and its treatment. Furthermore, these data point out to the role of 5-HT2CR in neuroplasticity and neuroinflammation.
Published:
2019-12
Title:
Insulin inhibits glucagon release by SGLT2-induced stimulation of somatostatin secretion
Authors:
Vergari, Elisa; Knudsen, Jakob G.; Ramracheya, Reshma; Salehi, Albert; Zhang, Quan; Adam, Julie; Asterholm, Ingrid Wernstedt; Benrick, Anna; Briant, Linford J. B.; Chibalina, Margarita V.; Gribble, Fiona M.; Hamilton, Alexander; Hastoy, Benoit; Reimann, Frank; Rorsman, Nils J. G.; Spiliotis, Ioannis I.; Tarasov, Andrei; Wu, Yanling; Ashcroft, Frances M.; Rorsman, Patrik
Abstract:
Published:
2019-12
Title:
Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw
Authors:
Woronowicz, Katherine C.; Schneider, Richard A.
Abstract:
The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition.
Published:
2019-12
Title:
RAGE is a Critical Mediator of Pulmonary Oxidative Stress, Alveolar Macrophage Activation and Emphysema in Response to Cigarette Smoke
Authors:
Sanders, Karl A.; Delker, Don A.; Huecksteadt, Tom; Beck, Emily; Wuren, Tanna; Chen, Yuntian; Zhang, Yuxia; Hazel, Mark W.; Hoidal, John R.
Abstract:
Published:
2019-12
Title:
Salicin inhibits AGE-induced degradation of type II collagen and aggrecan in human SW1353 chondrocytes: therapeutic potential in osteoarthritis
Authors:
Gao, Feng; Zhang, Shanyong
Abstract:
Osteoarthritis (OA) is a major age-related disease, which may be caused by the accumulation of advanced glycation end-products (AGEs). Excessive degradation of type II collagen and aggrecan by matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin type 1 motif (ADAMTS) induced by AGEs is a pivotal event in the pathogenesis of osteoarthritis. In addition, activation of the nuclear factor-κB (NF-κB) pathway induces the expression of a cascade of proinflammatory cytokines, such as interleukin (IL)-1β and tumor necrosis factor-α (TNF-α). In the present study, we investigated the effects of salicin, one of the main constituents of aspirin and a derivative of Alangium chinense, on AGE-induced degradation of the articular extracellular matrix in SW1353 human chondrocytes. Our findings reveal a novel beneficial role of salicin in rescuing degradation of type II collagen and aggrecan, reducing oxidative stress, attenuating expression of proinflammatory cytokines, and inhibiting activation of the NF-κB proinflammatory signaling pathway in chondrocytes stimulated with AGEs. Salicin may thus have potential as a safe and effective therapy against the development and progression of OA.
Published:
2019-12
Title:
The association between dietary fibre deficiency and high-income lifestyle-associated diseases: Burkitt's hypothesis revisited
Authors:
O'Keefe, Stephen J.
Abstract:
In 1969, Denis Burkitt published an article titled "Related disease-related cause?", which became the foundation for Burkitt's hypothesis. Working in Uganda, he noted that middle-aged people (40-60 years old) had a much lower incidence of diseases that were common in similarly aged people living in England, including colon cancer, diverticulitis, appendicitis, hernias, varicose veins, diabetes, atherosclerosis, and asthma, all of which are associated with lifestyles commonly led in high-income countries (HICs; also known as western diseases). Following Cleave's common cause hypothesis-which suggests that if a group of diseases occur together in the same population or individual, they are likely to have a common cause-Burkitt attributed these diseases to the small quantities of dietary fibre consumed in HICs due mainly to the over-processing of natural foods. Nowadays, dietary fibre intake in HICs is around 15 g/day (well below the amount of fibre Burkitt advocated of >50 g/day-which is associated with diets from rural, southern and eastern sub-Sahalean Africa). Since Burkitt's death in 1993, his hypothesis has been verified and extended by large-scale epidemiological studies, which have reported that fibre deficiency increases the risk of colon, liver, and breast cancer and increases all cancer mortality and death from cardiovascular, infectious, and respiratory diseases, diabetes, and all non-cardiovascular, non-cancer causes. Furthermore, mechanistic studies have now provided molecular explanations for these associations, typified by the role of short-chain fatty acids, products of fibre fermentation in the colon, in suppressing colonic mucosal inflammation and carcinogenesis. Evidence suggests that short-chain fatty acids can affect the epigenome through metabolic regulatory receptors in distant organs, and that this can reduce obesity, diabetes, atherosclerosis, allergy, and cancer. Diseases associated with high-income lifestyles are the most serious threat to health in developed countries, and public and governmental awareness needs to be improved to urge an increase in intake of fibre-rich foods. This Viewpoint will summarise the evidence that suggests that increasing dietary fibre intake to 50 g/day is likely to increase lifespan, improve the quality of life during the added years, and substantially reduce health-care costs.
Published:
2019-12
Title:
Macrophages and cadherins in fibrosis and systemic sclerosis
Authors:
To, Sarah; Agarwal, Sandeep K.
Abstract:
Purpose of review Macrophages are key players in systemic sclerosis (SSc) and fibrosis. The mechanism by which macrophages regulate fibrogenesis is unclear and understanding the origin and function of macrophages is critical to developing effective therapeutics. Novel targets on macrophages are under investigation and recently, cadherins have emerged as a potential therapeutic target on macrophages. The current review will discuss the importance of macrophages in SSc and fibrosis and summarize recent studies on the role of cadherin-11 (Cdh11) on macrophages and fibrosis. Recent findings Genome-wide expression studies demonstrate the importance of macrophages in SSc and fibrosis. Although M2 macrophages are associated with fibrosis, the presence of a mixed M1/M2 phenotype in fibrosis has recently been reported. Several studies aiming to identify macrophage subsets involved in fibrogenesis suggest that monocyte-derived alveolar macrophages are key players in the development of murine lung fibrosis. Recent functional studies show that Cdh11 regulates macrophages, fibroblast invasion, and adhesion of macrophages to myofibroblasts. Summary Macrophages play an important role in SSc and fibrosis. New insights into the mechanisms by which macrophages regulate fibrogenesis have been discovered on the basis of Cdh11 studies and suggest that targeting Cdh11 may be an effective target to treat fibrosis.
Published:
2019-11
Title:
Acidity promotes tumour progression by altering macrophage phenotype in prostate cancer
Authors:
El-Kenawi, Asmaa; Gatenbee, Chandler; Robertson-Tessi, Mark; Bravo, Rafael; Dhillon, Jasreman; Balagurunathan, Yoganand; Berglund, Anders; Visvakarma, Naveen; Ibrahim-Hashim, Arig; Choi, Jung; Luddy, Kimberly; Gatenby, Robert; Pilon-Thomas, Shari; Anderson, Alexander; Ruffell, Brian; Gillies, Robert
Abstract:
Tumours rapidly ferment glucose to lactic acid even in the presence of oxygen, and coupling high glycolysis with poor perfusion leads to extracellular acidification. We hypothesise that acidity, independent from lactate, can augment the pro-tumour phenotype of macrophages. We analysed publicly available data of human prostate cancer for linear correlation between macrophage markers and glycolysis genes. We used zwitterionic buffers to adjust the pH in series of in vitro experiments. We then utilised subcutaneous and transgenic tumour models developed in C57BL/6 mice as well as computer simulations to correlate tumour progression with macrophage infiltration and to delineate role of acidity. Activating macrophages at pH 6.8 in vitro enhanced an IL-4-driven phenotype as measured by gene expression, cytokine profiling, and functional assays. These results were recapitulated in vivo wherein neutralising intratumoural acidity reduced the pro-tumour phenotype of macrophages, while also decreasing tumour incidence and invasion in the TRAMP model of prostate cancer. These results were recapitulated using an in silico mathematical model that simulate macrophage responses to environmental signals. By turning off acid-induced cellular responses, our in silico mathematical modelling shows that acid-resistant macrophages can limit tumour progression. This study suggests that tumour acidity contributes to prostate carcinogenesis by altering the state of macrophage activation.
Published:
2019-10
Title:
Fasting as a therapy in neurological disease
Authors:
Phillips, Matthew C.L.
Abstract:
Fasting is deeply entrenched in evolution, yet its potential applications to today's most common, disabling neurological diseases remain relatively unexplored. Fasting induces an altered metabolic state that optimizes neuron bioenergetics, plasticity, and resilience in a way that may counteract a broad array of neurological disorders. In both animals and humans, fasting prevents and treats the metabolic syndrome, a major risk factor for many neurological diseases. In animals, fasting probably prevents the formation of tumors, possibly treats established tumors, and improves tumor responses to chemotherapy. In human cancers, including cancers that involve the brain, fasting ameliorates chemotherapy-related adverse effects and may protect normal cells from chemotherapy. Fasting improves cognition, stalls age-related cognitive decline, usually slows neurodegeneration, reduces brain damage and enhances functional recovery after stroke, and mitigates the pathological and clinical features of epilepsy and multiple sclerosis in animal models. Primarily due to a lack of research, the evidence supporting fasting as a treatment in human neurological disorders, including neurodegeneration, stroke, epilepsy, and multiple sclerosis, is indirect or non-existent. Given the strength of the animal evidence, many exciting discoveries may lie ahead, awaiting future investigations into the viability of fasting as a therapy in neurological disease.
Published:
2019-10
Title:
Inhibiting the formation of advanced glycation end-products by three stilbenes and the identification of their adducts
Authors:
Wang, Weixin; Yang, Rui; Yao, Huan; Wu, Yun; Pan, Weidong; Jia, Ai-Qun
Abstract:
The objective of this work is to investigate the inhibition effects on AGEs formation and the ability of scavenging toxic carbonyls of three stilbenes, resveratrol, oxyresveratrol, and piceatannol. The results showed that the three stilbenes had the activity to inhibit the AGEs formation in BSA-acrolein and BSA-methylglyoxal models, especially piceatannol which showed the strongest inhibition effects on the formation of AGEs with the half maximal inhibitory concentrations (IC50) value of 2.44 mM and 0.19 mM in the BSA-acrolein and BSA-methylglyoxal model, respectively. In addition, the three stilbenes showed the ability to scavenge acrolein and methylglyoxal in pH 7.4 at 37 °C. Eight isolated adducts between three stilbenes and toxic carbonyls further confirmed that these three stilbenes could scavenge acrolein and methylglyoxal by forming adducts successfully. Thus, the present study suggested that the consumption of foods containing stilbenes was beneficial for controlling the amount of reactive carbonyl species and the AGEs formation.
Published:
2019-10
Title:
Intergenerational Metabolic Syndrome and Neuronal Network Hyperexcitability in Autism
Authors:
Rivell, Aileen; Mattson, Mark P.
Abstract:
We review evidence that suggests a role for excessive consumption of energy-dense foods, particularly fructose, and consequent obesity and insulin resistance (metabolic syndrome) in the recent increase in prevalence of autism spectrum disorders (ASD). Maternal insulin resistance, obesity, and diabetes may predispose offspring to ASD by mechanisms involving chronic activation of anabolic cellular pathways and a lack of metabolic switching to ketosis resulting in a deficit in GABAergic signaling and neuronal network hyperexcitability. Metabolic reprogramming by epigenetic DNA and chromatin modifications may contribute to alterations in gene expression that result in ASD. These mechanistic insights suggest that interventions that improve metabolic health such as intermittent fasting and exercise may ameliorate developmental neuronal network abnormalities and consequent behavioral manifestations in ASD.
Published:
2019-10
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