Sexual Dimorphism in Lipid Metabolism and Gut Microbiota in Mice Fed a High-Fat Diet

Abstract

The gut microbiome plays an essential role in regulating lipid metabolism. However, little is known about how gut microbiome modulates sex differences in lipid metabolism. The present study aims to determine whether gut microbiota modulates sexual dimorphism of lipid metabolism in mice fed a high-fat diet (HFD). Conventional and germ-free male and female mice were fed an HFD for four weeks, and lipid absorption, plasma lipid profiles, and apolipoprotein levels were then evaluated. The gut microbiota was analyzed by 16S rRNA gene sequencing. After 4-week HFD consumption, the females exhibited less body weight gain and body fat composition and significantly lower triglyceride levels in very-low-density lipoprotein (VLDL) and cholesterol levels in high-density lipoprotein (HDL) compared to male mice. The fecal microbiota analysis revealed that the male mice were associated with reduced gut microbial diversity. The female mice had considerably different microbiota composition compared to males, e.g., enriched growth of beneficial microbes (e.g., Akkermansia) and depleted growth of Adlercreutzia and Enterococcus. Correlation analyses suggested that the different compositions of the gut microbiota were associated with sexual dimorphism in body weight, fat mass, and lipid metabolism in mice fed an HFD. Our findings demonstrated significant sex differences in lipid metabolism and the microbiota composition at baseline (during LFD), along with sex-dependent responses to HFD. A comprehensive understanding of sexual dimorphism in lipid metabolism modulated by microbiota will help to develop more sex-specific effective treatment options for dyslipidemia and metabolic disorders in females.

Effects of Soluble Dextrin Fiber from Potato Starch on Body Weight and Associated Gut Dysbiosis Are Evident in Western Diet-Fed Mice but Not in Overweight/Obese Children

“…Gonadal hormones can alter the gut microbiome that has been reported in humans and rodents [42]. Significant sex differences in lipid metabolism and microbiota composition at baseline, along with sex-dependent responses to a high-fat diet (HFD), have recently been reported [42].…”

“…Gonadal hormones can alter the gut microbiome that has been reported in humans and rodents [42]. Significant sex differences in lipid metabolism and microbiota composition at baseline, along with sex-dependent responses to a high-fat diet (HFD), have recently been reported [42]. Female mice exhibited less body weight gain and body fat composition, accompanied by an enriched growth of beneficial microbes (e.g., Akkermansia) and depleted growth of Adlercreutzia and Enterococcus.…”

Variations in the Relative Abundance of Gut Bacteria Correlate with Lipid Profiles in Healthy Adults

“…The differential regulation can be partially explained by the two-way interaction between gut bacteria and sex hormones, as well as differences in primary and secondary bile acid levels between genders [96,97]. Therefore, gender can serve as a significant confounder for correlations between host lipid profiles and gut bacteria [87,[97][98][99].…”