Dietary Genistein Could Modulate Hypothalamic Circadian Entrainment, Reduce Body Weight, and Improve Glucose and Lipid Metabolism in Female Mice

Abstract

Genistein has beneficial effects on metabolic disorders. However, the specific mechanism is not clearly understood. In light of the significant role of the hypothalamus in energy and metabolic homeostasis, this study was designed to explore whether dietary genistein intake could mitigate the harmful effects of a high-fat diet on glucose and lipid metabolism and whether any alterations caused by dietary genistein were associated with hypothalamic gene expression profiles. C57BL/6 female mice were fed a high-fat diet without genistein (HF), a high-fat diet with genistein (HFG), or a normal control diet (CON) for 8 weeks. Body weight and energy intake were assessed. At the end of the study, glucose tolerance and serum levels of insulin and lipids were analyzed. Hypothalamic tissue was collected for whole transcriptome sequencing and reverse transcription quantitative PCR (RT-qPCR) validation. Energy intake and body weight were significantly reduced in the mice of the HFG group compared with those of the HF group. Mice fed the HFG diet had improved glucose tolerance and decreased serum triacylglycerol, free fatty acids, and low-density lipoprotein cholesterol compared with those fed the HF diet. The HFG diet also modulated gene expression in the hypothalamus; the most abundant genes were enriched in the circadian entrainment pathway. Dietary genistein intake could reduce body weight, improve glucose and lipid metabolism, and regulate hypothalamic circadian entrainment. The ability of genistein intake to influence regulation of the hypothalamic circadian rhythm is important since this could provide a novel target for the treatment of obesity and diabetes.

Flavonoids and Their Anti-Diabetic Effects: Cellular Mechanisms and Effects to Improve Blood Sugar Levels

“…Genistein demonstrated an inhibitory effect on tyrosine kinase which dysregulates glucose homeostasis (Figure 3) [199]. The administration of genistein to mice reduced body weight and improved glucose and lipid metabolism [200]. A transcriptome analysis revealed that genistein could affect the regulation of the hypothalamic circadian rhythms which could provide a novel target for the therapy of diabetes and obesity.…”

Gut microbiota might be a crucial factor in deciphering the metabolic benefits of perinatal genistein consumption in dams and adult female offspring

“…The serum insulin concentrations, total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and free fatty acids (FFA) were measured as previously described. 22 Insulin sensitivity was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). The HOMA-IR was calculated as previously described.…”

Exercise and/or Genistein Treatment Impact Gut Microbiota and Inflammation after 12 Weeks on a High-Fat, High-Sugar Diet in C57BL/6 Mice

“…Genistein, the most abundant isoflavone in soy, is metabolized by gut bacteria into numerous metabolites [16] that target and modulate estrogen-dependent and non-estrogenic activity pathways with a wide variety of biological activities (e.g., the reduction of inflammation) [17][18][19][20]. Recently, genistein has been highlighted to have the capacity to reduce inflammation, modify adipocyte functioning, and maintain body weight [21][22][23][24][25][26].…”