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Journal Article Research Support, Non-U.S. Gov't Epublish 29 citations

PubMed: 37770988 DOI: 10.1186/s13293-023-00543-6

Sex differences in obesity-induced renal lipid accumulation revealed by lipidomics: a role of adiponectin/AMPK axis.

Biol Sex Differ 14(1):63

Authors: Florian Juszczak, Louise Pierre, Morgane Decarnoncle, Inès Jadot, Blanche Martin, Olivia Botton, Nathalie Caron, Jonas Dehairs, Johannes V Swinnen, Anne-Emilie Declèves

Affiliations

  • Laboratory of Metabolic and Molecular Biochemistry, Faculty of Medicine and Pharmacy, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Mons, Belgium.
  • Molecular Physiology Research Unit (URPhyM), Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium.
  • Laboratory of Metabolic and Molecular Biochemistry, Faculty of Medicine and Pharmacy, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Mons, Belgium.
  • Biochemistry and Cellular Biology Research Unit (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium.
  • Molecular Physiology Research Unit (URPhyM), Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium.
  • Laboratory of Lipid Metabolism and Cancer, Department of Oncology, KU Leuven, Leuven, Belgium.

Abstract

BACKGROUND

Sex differences have been observed in the development of obesity-related complications in patients, as well as in animal models. Accumulating evidence suggests that sex-dependent regulation of lipid metabolism contributes to sex-specific physiopathology. Lipid accumulation in the renal tissue has been shown to play a major role in the pathogenesis of obesity-induced kidney injury. Unlike in males, the physiopathology of the disease has been poorly described in females, particularly regarding the lipid metabolism adaptation.

METHODS

Here, we compared the lipid profile changes in the kidneys of female and male mice fed a high-fat diet (HFD) or low-fat diet (LFD) by lipidomics and correlated them with pathophysiological changes.

RESULTS

We showed that HFD-fed female mice were protected from insulin resistance and hepatic steatosis compared to males, despite similar body weight gains. Females were particularly protected from renal dysfunction, oxidative stress, and tubular lipid accumulation. Both HFD-fed male and female mice presented dyslipidemia, but lipidomic analysis highlighted differential renal lipid profiles. While both sexes presented similar neutral lipid accumulation with obesity, only males showed increased levels of ceramides and phospholipids. Remarkably, protection against renal lipotoxicity in females was associated with enhanced renal adiponectin and AMP-activated protein kinase (AMPK) signaling. Circulating adiponectin and its renal receptor levels were significantly lower in obese males, but were maintained in females. This observation correlated with the maintained basal AMPK activity in obese female mice compared to males.

CONCLUSIONS

Collectively, our findings suggest that female mice are protected from obesity-induced renal dysfunction and lipotoxicity associated with enhanced adiponectin and AMPK signaling compared to males.

MeSH

Adiponectin, Kidney, Diet, Sex Characteristics, Obesity, Sex, Lipidomics, Sex Differences

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