Genistein protects against hyperglycemia and fatty liver disease in diet-induced prediabetes mice via activating hepatic insulin signaling pathway

Abstract

IntroductionInsulin signaling via the insulin receptor (IR) may be associated with the amelioration of diet-induced metabolic syndrome. Genistein, a soy isoflavone, has been suggested to play a role in the amelioration of high-fat diet-induced metabolic disorders.MethodsHere, we aimed to explore whether genistein regulates glucose and hepatic lipid by activating the insulin signaling pathway in diet-induced obesity mice.ResultsWe showed that treatment of western-style diet-fed mice with genistein (60 mg/kg) significantly improved insulin resistance with decreased hyperglycemia and HOMA-IR index. These effects were linked to activating hepatic IRβ/PI3K/Akt signaling. Furthermore, genistein suppressed gluconeogenesis and promoted glycogen synthesis to maintain glucose homeostasis by increasing the phosphorylation of hepatic FOXO1/GSK3β in vivo and in vitro. The reduced level of insulin and upregulation of insulin signaling in genistein-treated mice also lead to an increase in hepatic energy status by inducing energy-sensing AMPK, reducing hepatic SREBP1c/ACC/FAS without affecting β-oxidation to prevent hepatic lipid accumulation. The protective effect of genistein on hepatic lipid accumulation was also validated in vitro. Besides, genistein had little effect on improvements in intestinal function and liver inflammation.ConclusionTaken together, our results showed that genistein prevents insulin resistance and hyperglycemia through improvements in hepatic function. This study provides new insight into the mechanisms of genistein mediating glucose metabolism and suggests that genistein may be a promising diet ingredient for preventing prediabetes and hepatic lipid accumulation.

Effect of different processing practices on physicochemical parameters, phenolic compounds, and antioxidant properties of chia seed oils

“…It's interesting to note that other oilseeds lack the majority of the phenolic compound found in chia seed oil (Tuberoso et al, 2007). In addition to antioxidant effects, polyphenols have other beneficial effects, such as genistein, which can prevent insulin resistance and hyperglycemia by improving liver function (Zhang, Zhang, et al, 2022).…”

A potential therapeutic approach for ulcerative colitis: targeted regulation of macrophage polarization through phytochemicals

“…Genistein, an isoflavonoid compound widely distributed in soy-based products ( 78 ), also called phytoestrogen owing to a pattern resembling estradiol, shows high anti-inflammatory, anticancer, antioxidant, and antidiabetic properties and has attracted interest in medical research ( 64 , 79 , 80 ). Recently, it has been revealed that genistein could conspicuously mitigate experimental colitis, which is associated with targeting macrophage polarization.…”

Inverse association between isoflavones and prediabetes risk: evidence from NHANES 2007–2010 and 2017–2018

“…Among flavonoids, isoflavones, including daidzein, genistein, and glycitein, are abundant in legumes, specifically soybeans and soy products. Although the blood glucose control effects of isoflavones have been observed in animal experiments ( 14 ), there is currently a limited amount of epidemiological research and clinical trials examining the association between isoflavones and prediabetes ( 15 ). Therefore, our study aims to fill a research gap by investigating the relationship between flavonoids, particularly isoflavones, and prediabetes risk.…”