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

Marcela González-Granillo, Luisa A. Helguero, Eliana Alves, Amena Archer, Christina Savva, Matteo Pedrelli, Osman Ahmed, Xidan Li, Maria Rosário Domingues, Paolo Parini, Jan Åke Gustafsson, Marion Korach-André

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish (US)
Article number11
JournalBiology of Sex Differences
Volume10
Issue number1
DOIs
StatePublished - Feb 26 2019

Keywords

  • Fatty acids
  • Lipidomics
  • Metabolic syndrome
  • Obesity
  • Sex

ASJC Scopus subject areas

  • Gender Studies
  • Endocrinology

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