Abstract
Bioactive food components have gained growing attention in recent years. Multitude of studies have demonstrated that genistein, as a soy-derived phytoestrogen, has beneficial effects on metabolism. However, the exact mechanism by which genistein improving metabolic disorders remains unclear, especially the central regulation. This study was designed to evaluate whether addition of genistein to the high-fat diet could counter the metabolic disorders and whether these alterations were associated with the gene expression in hypothalamus. C57BL/6 mice were fed either a high-fat diet (HF), high-fat diet with genistein (0.25g/kg diet) (HFG) or a normal control diet (CON) for eight weeks. Body weight were assessed during the study. After eight-week intervention, content of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and brown adipose tissue (BAT) were weighed. Glucose tolerance test, the serum levels of insulin and lipid were assessed. The mRNA of browning marker was detected in the WAT. The hypothalamus was collected for whole transcriptome sequencing and reverse transcription quantitative PCR (RT-qPCR) validation. The results demonstrated that mice fed the HFG diet had lower body weight (p<0.05) and SAT mass (p<0.01), decrease levels of low-density lipoprotein cholesterol (LDL-C) (p<0.01) and free fatty acids (FFA) (p<0.05), higher browning marker of Ucp1 (p<0.01) and Cidea (p<0.05) in WAT and an improvement in glucose tolerance and insulin sensitivity compared with those in the HF group. Transcriptome sequencing showed that there were three differentially expressed genes in hypothalamus among the three groups, including Ucn3 (p<0.05), Depp (p<0.01) and Stc1 (p<0.01). Thus, regulating gene expressions in hypothalamus is a potential mechanism for genistien improving metabolism and inducing WAT browning, which may provide a novel target for the precaution and treatment of T2DM. Disclosure L. Zhou: None. X. Xiao: None. M. Deng: None. J. Liu: None. M. Yu: None. Funding National Natural Science Foundation of China
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