Dataset Information

Sexual dimorphism in adipose tissue mitochondrial function and metabolic flexibility in obesity.

ABSTRACT:

Objective

The prevalence of obesity is growing globally. Adiposity increases the risk for metabolic syndrome, type 2 diabetes and cardiovascular disease. Adipose tissue distribution influences systemic metabolism and impacts metabolic disease risk. The link between sexual dimorphisms of adiposity and metabolism is poorly defined. We hypothesise that depot-specific adipose tissue mitochondrial function contributes to the sexual dimorphism of metabolic flexibility in obesity.

Methods

Male and female mice fed high fat diet (HFD) or standard diet (STD) from 8-18 weeks of age underwent whole animal calorimetry and high-resolution mitochondrial respirometry analysis on adipose tissue depots. To determine translatability we used RT-qPCR to examine key brown adipocyte-associated gene expression: peroxisome proliferator-activated receptor co-activator 1α, Uncoupling protein 1 and cell death inducing DFFA like effector a in brown adipose tissue (BAT) and subcutaneous adipose tissue (sWAT) of 18-week-old mice and sWAT from human volunteers.

Results

Male mice exhibited greater weight gain compared to female mice when challenged with HFD. Relative to increased body mass, the adipose to body weight ratio for BAT and sWAT depots was increased in HFD-fed males compared to female HFD-fed mice. Oxygen consumption, energy expenditure, respiratory exchange ratio and food consumption did not differ between males and females fed HFD. BAT mitochondria from obese females showed increased Complex I & II respiration and maximal respiration compared to lean females whereas obese males did not exhibit adaptive mitochondrial BAT respiration. Sexual dimorphism in BAT-associated gene expression in sWAT was also associated with Body Mass Index in humans.

Conclusions

We show that sexual dimorphism of weight gain is reflected in mitochondrial respiration analysis. Female mice have increased metabolic flexibility to adapt to changes in energy intake by regulating energy expenditure through increased complex II and maximal mitochondrial respiration within BAT when HFD challenged and increased proton leak in sWAT mitochondria.

SUBMITTER: MacCannell ADV

PROVIDER: S-EPMC8310795 | biostudies-literature |

REPOSITORIES: biostudies-literature

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