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 [Lipids]

³Nutrition and Health Research Group, Technological Center for Nutrition and Health, Tecnio, Campus of International Excellence Southern Catalonia (CEICS), Reus, Spain;
⁴Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom;
⁵Nutrigenomics Research Group, Department of Biochemistry and Biotechology, University Rovira i Virgili, Tarragona, Spain; and
⁶National Institute for Health Research Southampton Biomedical Research Centre, University Hospital Southampton National Health Service Foundation Trust and University of Southampton, Southampton, United Kingdom

↵*To whom correspondence should be addressed. E-mail: antoni.caimari{at}ctns.cat.

↵1 Supported by the European Commission through its Seventh Framework Programme, BIOmarkers of Robustness of Metabolic Homeostasis for Nutrigenomics-derived Health CLAIMS Made on Food (grant agreement no. 244995). CPC was supported by a scholarship from the National Council of Science and Technology, Mexico (CONACYT). MIR-N was supported by the scholarship PTQ-12-05810 from the Ministry of Economy and Competitiveness (MINECO) of the Spanish Goverment.
↵2 Supplemental Figure 1 and Supplemental Table 1 are available from the “Online Supporting Material” link in the online posting of the article and from the same link in the online table of contents at http://ajcn.nutrition.org.

Abstract

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.

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