Impairment of lysophospholipid metabolism in obesity: altered plasma profile and desensitization to the modulatory properties of n-3 polyunsaturated fatty acids in a randomized controlled trial

BACKGROUND: Plasma lysophospholipids have emerged as signaling molecules with important effects on inflammation, insulin resistance, and fatty liver disease, each of which is linked closely to obesity. Dietary n-3 (ω-3) polyunsaturated fatty acids (PUFAs) may be able to improve these conditions. OBJECTIVE: The objective of this study was to assess the response of plasma lysophospholipids to obesity, n-3 PUFA consumption, and a high-fat meal challenge to better understand the role of lysophospholipid metabolism in the progression of obesity-related disorders. DESIGN: We determined the concentrations of 8 lysophosphatidylcholines, 11 lysophosphatidylethanolamines, and 7 lysophosphatidylinositols in the plasma of 34 normal-weight and 38 obese subjects randomly assigned to consume corn oil (control) or n-3 PUFA-rich fish oil (3 g/d; n = 15-19/group) for 90 d. Blood samples were collected on the last day of the study under fasting conditions and 6 h after a high-fat meal (1135 kcal, 86 g fat) challenge. The profile of secreted lysophospholipids was studied in HepG2 cells under palmitate-induced steatosis. RESULTS: Obese and normal-weight subjects had different profiles of plasma lysophospholipids. A multivariate combination of the 26 lysophospholipids could discriminate between normal-weight and obese subjects with an accuracy of 98%. The high-fat meal challenge altered the concentration of plasma lysophosphatidylcholines in an oil treatment-dependent manner in normal-weight but not obese subjects, suggesting that obesity impairs the sensitivity of lysophospholipid metabolism to n-3 PUFAs. Noncytotoxic steatosis in HepG2 cells affected the secretion pattern of lysophospholipids, partially resembling the changes observed in the plasma of obese subjects. CONCLUSIONS: Obesity has a substantial impact on lysophospholipid metabolism, altering the plasma lysophospholipid profile and abolishing its sensitivity to dietary n-3 PUFAs. These effects could contribute to the onset or progression of alterations associated with obesity, such as inflammation, insulin resistance, and fatty liver disease. This trial was registered at www.controlled-trials.com as ISRCTN96712688.