Difference in effect of HFD on intestinal microflora, fat metabolism, and brain microglia activation between female and male SD rats

Abstract:

[Objective] To investigate the effect of high-fat diet (HFD) on intestinal microflora and expression levels of inflammatory cytokines in hypothalamic paraventricular nucleus (PVN) of female and male Sprague-Dawley (SD) rats. [Methods] A total of 24 3-week-old SD rats (12 males) were randomized into 4 groups (6 per group). They were given either control diet (male control group, CM; female control group, CF) or the 60% fat diet (high-fat male group, HM; high-fat female group, HF) until 10 weeks old when the fresh feces were collected and total genomic DNA was extracted. For high-throughput sequencing analysis, we amplified the V3+V4 regions of bacterial 16S rDNA by PCR (polymerase chain reaction). The content of short-chain fatty acids (SCFAs) in the caecal contents of rats was analyzed by gas chromatography. Real-time PCR was performed to analyze the mRNA expression of microglial marker CD11b and inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the PVN. [Results]Reduction in quantity and diversity of intestinal microflora in the HM group (P<0.05) and decrease in abundance of the flora in HF group (P<0.05) were observed compared with those in the respective control groups. The acetic acid content in cecum was lower (P< 0.05), and mRNA expression of CD11b in PVN was higher (P<0.05) in HM group than in CM group. [Conclusion] HFD can alter the intestinal microflora of female and male rats, leading to the flora imbalance. However, the effect of HFD on intestinal microflora and brain microglia is different between female and male rats. The HFD-induced variation of intestinal microflora in male rats may be associated with brain microglia activation.