Effect of betaine on hepatic insulin resistance through FOXO1-induced NLRP3 inflammasome

The Journal of Nutritional Biochemistry
Dae Hyun KimHae Young Chung

Abstract

In the present study, we attempted to elucidate whether molecular modulation of inflammation by betaine through the forkhead box O1 (FOXO1)-induced NLRP3 inflammasome improves insulin resistance. Betaine is a major water-soluble component of Lycium chinense. It mainly functions as an oxidative metabolite of choline by suppressing superoxide-induced free radicals by donating methyl groups. The FOXO1 transcription factor regulates various genes involved in cellular metabolic processes related to cell death as well as oxidative stress responses through binding to the thioredoxin-interacting protein (TXNIP). Betaine is known to inhibit FOXO1 phosphorylation through phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) in liver cells exposed to insulin. To elucidate the molecular mechanism of inactivation of insulin-induced FOXO1 by the antioxidant betaine, we used HepG2 cells and the liver of db/db mice treated with betaine at a dose of 50 mg/kg/day for 3 weeks. We found that the activation of NLRP3 inflammasome genes was reduced by betaine, which resulted in the suppression of reactive species (RS) production in liver cells. In addition, betaine inhibited insulin-induced PI3K/AKT and FOXO1 activation. Therefore, betaine suppress...Continue Reading

Citations

Dec 6, 2018·Frontiers in Immunology·Yaoyao XiaWenkai Ren
May 24, 2019·Frontiers in Pharmacology·Gulcin TezcanSvetlana F Khaiboullina
Jun 9, 2018·Frontiers in Immunology·Guangfu ZhaoYuanyi Peng
Dec 15, 2019·Biomolecules·Sujuan DingJun Fang
Oct 28, 2020·Journal of Cellular and Molecular Medicine·Jingjin LiuZhengyuan Xia
Feb 9, 2021·Journal of Diabetes and Metabolic Disorders·Pouya SalahiMasoud Alirezaei
Oct 21, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yali ZhangWeiguo Andy Tao
May 18, 2020·Behavioural Brain Research·Shahin HassanpourSeyyed Mojtaba Razavi

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