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Sex-specific lipid molecular signatures in obesity-associated metabolic dysfunctions revealed by lipidomic characterization in ob/ob mouse.

ABSTRACT: The response to overfeeding is sex dependent, and metabolic syndrome is more likely associated to obesity in men or postmenopausal women than in young fertile women. We hypothesized that obesity-induced metabolic syndrome is sex dependent due to a sex-specific regulation of the fatty acid (FA) synthesis pathways in liver and white adipose depots. We aimed to identify distinctive molecular signatures between sexes using a lipidomics approach to characterize lipid species in liver, perigonadal adipose tissue, and inguinal adipose tissue and correlate them to the physiopathological responses observed. Males had less total fat but lower subcutaneous on visceral fat ratio together with higher liver weight and higher liver and serum triglyceride (TG) levels. Males were insulin resistant compared to females. Fatty acid (FA) and TG profiles differed between sexes in both fat pads, with longer chain FAs and TGs in males compared to that in females. Remarkably, hepatic phospholipid composition was sex dependent with more abundant lipotoxic FAs in males than in females. This may contribute to the sexual dimorphism in response to obesity towards more metaflammation in males. Our work presents an exhaustive novel description of a sex-specific lipid signature in the pathophysiology of metabolic disorders associated with obesity in ob/ob mice. These data could settle the basis for future pharmacological treatment in obesity.

SUBMITTER: Gonzalez-Granillo M

PROVIDER: S-EPMC6390380 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Sex-specific lipid molecular signatures in obesity-associated metabolic dysfunctions revealed by lipidomic characterization in ob/ob mouse.

González-Granillo Marcela M Helguero Luisa A LA Alves Eliana E Archer Amena A Savva Christina C Pedrelli Matteo M Ahmed Osman O Li Xidan X Domingues Maria Rosário MR Parini Paolo P Gustafsson Jan-Åke JÅ Korach-André Marion M

Biology of sex differences 20190226 1

The response to overfeeding is sex dependent, and metabolic syndrome is more likely associated to obesity in men or postmenopausal women than in young fertile women. We hypothesized that obesity-induced metabolic syndrome is sex dependent due to a sex-specific regulation of the fatty acid (FA) synthesis pathways in liver and white adipose depots. We aimed to identify distinctive molecular signatures between sexes using a lipidomics approach to characterize lipid species in liver, perigonadal adi ...[more]

PMID: 30808418

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Project description:ObjectiveThe human lipidomic profile reflects lipid metabolism, including the early phase of pathophysiological changes associated with diseases. An investigation of the association between the plasma lipidomic profile and adolescent obesity might provide new insights into the biological mechanisms of obesity. Therefore, we aimed to investigate the association of the plasma lipidome with obesity in Chinese adolescents using lipidomics.MethodsUsing a combination of liquid chromatography and electrospray ionization tandem mass spectrometry, we quantified 328 lipid species from 24 lipid classes and subclasses in 100 male adolescents aged 14-16 years who were categorized into four groups: (1) normal weight with traditional normal clinical plasma lipid levels (NN); (2) normal weight with traditional abnormal clinical plasma lipid levels (NA); (3) obese with traditional normal clinical plasma lipid levels (ON); and (4) obese with traditional abnormal clinical plasma lipid levels (OA). The concentrations of all the lipid species were compared between obese and normal-weight adolescents at different traditional clinical plasma lipid levels using the Kruskal-Wallis test followed by the Mann-Whitney U test. A partial least squares discriminant analysis (PLS-DA) was applied to select lipids with a significant ability to discriminate adolescent obesity.ResultsThe lipidomic profile distinguished obese adolescents from normal-weight subjects. Regardless of whether traditional clinical plasma lipid levels were normal or abnormal, we observed a significant reduction in the levels of five lysophosphatidylcholines (LPC) species (LPC18:2, LPC18:1, LPC20:2, LPC20:1, and LPC20:0) in the obese group compared with the normal-weight group (difference = -31.29% to -13.19%; P=9.91 × 10-5 to 2.28 × 10-2). The ability of these five LPC species to discriminate adolescent obesity was confirmed in the PLS-DA model.ConclusionsThe findings provided evidence for the association of some LPC species with adolescent obesity. The discriminatory effects of five LPC species were identified between normal-weight and obese adolescents, independent of traditional clinical plasma lipid levels. These results will provide a basis for validation in subsequent studies.

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Sex-specific lipid molecular signatures in obesity-associated metabolic dysfunctions revealed by lipidomic characterization in ob/ob mouse.

Publications

Sex-specific lipid molecular signatures in obesity-associated metabolic dysfunctions revealed by lipidomic characterization in ob/ob mouse.

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