AUTHOR=Zhang Nana , Zhang Weiyue , Guo Xinxin , Liu Jianlin , Li Shuying , Zhang Hongtai , Fan Bei 

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

JOURNAL=Frontiers in Nutrition

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.1072044

DOI=10.3389/fnut.2022.1072044

ISSN=2296-861X

ABSTRACT=Insulin 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. Here, we aimed to explore whether genistein regulates glucose and hepatic lipid by activating insulin signaling pathway in diet-induced obesity mice. We showed that treatment of western-style diet-fed mice with genistein (100mg/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 through 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. Besides, genistein had little effect on improvements in intestinal function and liver inflammation. Taken together, our results showed that genistein prevents insulin resistance and hyperglycemia through improvements in hepatic function. This study suggests that genistein has potential to be developed as nutritional intervention to prediabetes and hepatic lipid accumulation.