Abstract
BackgroundAccumulating evidence indicates that high-fat diet (HFD)-induced metabolic disorders are associated with dysbiosis of the gut microbiota. However, the sex-specific characteristics of the gut microbiota and its association with a sexually dimorphic response to a HFD remain unclear.MethodsMale and female mice were randomly assigned to receive a chow diet (CD) or HFD for 12 weeks. A group of HFD mice were pretreated with antibiotic cocktails for 4 weeks. Body weight, insulin sensitivity and the levels of serum metabolic parameters (blood glucose and insulin) were evaluated. 16S rRNA gene sequencing was performed to analyze the composition of the gut microbiota.ResultsHFD-induced body weight gain (BWG) was higher in male mice than in female mice. While insulin resistance was increased in the HFD group compared to CD group in male mice, there was no difference in insulin resistance among female mice. Antibiotic-pretreatment alleviated HFD-induced insulin resistance in male mice and elevated fasting blood glucose in female mice. The composition of the gut microbiota in male mice was remarkably different from that in female mice independent of diet. A higher abundance of the genera Parabacteroides, Lactobacillus, Bacteroides, and Bifidobacterium was observed in females than inmales. HFD feeding also influenced the structure of the gut microbiota, as it decreased the abundance of short-chain fatty acids-producing bacteria including Roseburia and Lachnospiraceae_NK4A136_group. Alterations in the gut microbiota in response to antibiotics followed by HFD were different between males and females, indicating sex-dependent sensitivity to antibiotics.ConclusionsWe identified that sex had a greater impact on the composition of gut microbiota than environmental factors (HFD and antibiotics). The enrichment of beneficial microbes in female mice may be associated with the resistance of female mice to HFD-induced metabolic disorders, which was weakened by antibiotic pretreatment.
Highlights
Obesity and the subsequent metabolic disorders, which are associated with lifestyle changes characterized by excess energy intake and reduced physical activity [1], are topics that have inevitably gained much attention worldwide
Sex differences in body weight gain (BWG) in response to a high-fat diet (HFD) and antibiotic pretreatment The body weight (BW) of mice in different groups changed over time (Fig. 1b)
This study showed sex-specific changes in metabolic parameters in mice when exposed to a HFD and that females exhibited increased resistance to diet-induced metabolic disorders compared to males. 16S Ribosomal RNA (rRNA) sequencing analysis revealed that the structure of the gut microbiota was influenced by both sex and HFD feeding, with sex having a larger impact than a HFD
Summary
Obesity and the subsequent metabolic disorders, which are associated with lifestyle changes characterized by excess energy intake and reduced physical activity [1], are topics that have inevitably gained much attention worldwide. Females tend to have greater insulin sensitivity, and a higher degree of adiposity is required in females to achieve the same metabolic disturbances [2]. Another in vivo study showed that male mice on an HFD displayed higher blood glucose levels and insulin levels and elevated fat mass compared to those in females, which demonstrated that sex is a significant modifier of the impact of an HFD [3]. Accumulating evidence indicates that high-fat diet (HFD)-induced metabolic disorders are associated with dysbiosis of the gut microbiota. The sex-specific characteristics of the gut microbiota and its association with a sexually dimorphic response to a HFD remain unclear
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