Difference In Effect Of HFD On Intestinal Microflora,Fat Metabolism,and Brain Microglia Activation Between Female And Male SD Rats

In this study,we investigated the effect of a high-fat diet on the intestinal microflora and expression levels of inflammatory cytokines in the hypothalamic paraventricular nucleus of female and male Sprague-Dawley rats.Twenty-four 3-week-old SD rats,including 12 males,were randomly divided into 4 groups(6 per group).They were fed either a control diet(male control group,CM;female control group,CF)or a 60% fat diet(high-fat male group,HM;high-fat female group,HF)until they were 10 weeks old,at which point their fresh feces were collected and total genomic DNA was extracted.For high-throughput sequencing analysis,we amplified the V3-V4 regions of bacterial 16S-r DNA by polymerase chain reaction.The content of short-chain fatty acids in the caecal contents of rats was analyzed by gas chromatography.Real-time PCR was performed to analyze the m RNA expression of the microglial marker CD11 b and the inflammatory cytokines TNF-α and IL-6 in the PVN.Compared with the control group,the total number and diversity of intestinal flora in the female and male high-fat groups were significantly decreased(P<0.05).The flora richness of the HF group was significantly decreased compared with the CF group(P<0.05).The difference of evolutionary history preservation in the HM group was significantly smaller than that in the CM group(P<0.01).The total number and diversity of intestinal flora in the HM group were significantly decreased(P<0.05).At the phylum level,the relative abundance of Proteobacteria and Bacteroidetes in the HM group was significantly lower than that in the CM group(P<0.05).Compared with the CF group,the relative abundance of Bacteroides in the HF group was significantly decreased(P<0.01),while the relative abundance of TM7 was significantly increased(P<0.05).At the genus level,compared with the CM group,the relative abundance of Sporosarcina and Turicibacter in the HM group was significantly increased(P<0.05),and the relative abundance of Allobaculum was extremely significantly increased(P<0.01).The relative abundance of Mucispirillum,Corynebacterium,and Ruminococcus decreased significantly(P<0.05).Compared with the CF group,the relative abundance of Jeotgalicoccus was significantly increased(P<0.05),and the relative abundance of Sporosarcina,Akkermansia and Oscillospira was extremely significantly increased(P<0.01).The relative abundance of Lactobacillus was significantly decreased(P<0.05),and the relative abundance of Prevotella was extremely significantly decreased(P<0.01).The acetic acid content in the HM group was significantly decreased compared with the CM group(P<0.05),and the CD11 b m RNA relative expression level in the PVN region was significantly increased(P<0.05).In conclusion,a high-fat diet can alter the intestinal microflora of female and male rats,leading to flora imbalance.However,the effect of HFD on intestinal microflora and brain microglia differs between female and male rats.The HFD-induced variation of intestinal microflora in male rats may be associated with brain microglia activation.