Dihydromyricetin ameliorates diet-induced obesity and promotes browning of white adipose tissue by upregulating IRF4/PGC-1α

Abstract

Background Promoting the browning of white adipose tissue (WAT) is a promising approach for the treatment of obesity and related comorbidities because it increases energy expenditure. In this study, we investigated whether Dihydromyricetin (DHM), a flavonoid component, could ameliorate diet-induced obesity through promoting the browning of WAT. Methods Male C57BL/6 J mice were received a high-fat diet (HFD) to induce obesity and subsequently were treated with DHM (100 mg/kg/day) or vehicle for 4 weeks. The effects of DHM on weight reduction and metabolic phenotype improvement were observed in the mice. The expression of genes and protein involved in browning of WAT were assessed in inguinal WAT (iWAT) of the mice. Then, the effect of DHM on the inducing browning program was verified in adipocytes differentiated from stromal vascular fraction (SVF) cells of mouse iWAT. Finally, the mechanism by which DHM improves the browning of WAT was explored using RNA-seq and luciferase reporter assay. Results We find that DHM reduces body weight, decreases WAT mass, improves glucose and lipid metabolic disorders, and ameliorates hepatic steatosis in diet-induced obese (DIO) mice. Further studies show that DHM induces WAT browning, which is manifested by increased expression of uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and enhanced mitochondrial activity in iWAT and primary adipocytes. In addition, we also find that DHM enhances interferon regulatory factor 4 (IRF4) expression, which is a key transcriptional regulator of PGC-1α. Conclusion Our findings identify that DHM prevents obesity by inducing the browning of WAT through the upregulation of IRF4/PGC-1α, which may have potential therapeutic implications for the treatment of obesity.

Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases

“…Since a comprehensive presentation of all is too verbose, we will concentrate on a couple of natural products, such as resveratrol, [642][643][644][645][646][647][648][649] curcumin, [650][651][652][653][654] berberine, 517,[655][656][657][658][659][660] quercetin, [661][662][663][664][665][666][667][668][669] or clinical drugs, which have been extensively investigated in different pathological models. Other representative compounds, including astragaloside IV, [670][671][672] baicalin, [673][674][675][676] dihydromyricetin, [676][677][678][679][680][681] isoliquiritigenin, 682,683 astragalus polysaccharide, 684,685 dexmedetomidine,…”

Sarcopenic Obesity: Involvement of Oxidative Stress and Beneficial Role of Antioxidant Flavonoids

“…It has multiple biological and pharmacological properties, including antioxidant, anti-inflammatory, anti-cancer, neuroprotective, and hepatoprotective actions [197][198][199][200][201]. Some studies have also demonstrated that dihydromyricetin prevents obesity in HFD-fed and ob/ob mice and that its role in adipogenesis inhibition, adipocyte browning activation, and gut microbiota regulation is related to its anti-obesity effect [202][203][204][205].…”

Research progress of dihydromyricetin in the treatment of diabetes mellitus

“…Currently, organic polymer materials are incorporated to facilitate the biological utilization of DMY, and to develop a more effective drug for clinical treatment of DM. the latest research have found that adipose tissue is the key organ for DMY to function, adipose tissue is multifunctional and plays an important role in whole-body energy homeostasis in DM, Lipid metabolism disorder is one of the pathological processes of DM ( 67 , 68 ), it is reported that DMY had the capacity to decrease body weight, improve metabolic disorders of glucose and lipids and increase the consumption of energy by inducing WAT browning and offered new insight into the therapeutic action of this small molecule compound in obesity( 69 ). Although lipid metabolism disorder is one of the pathological processes of diabetes, DMY may also had ability to improve metabolic disorders of glucose and lipids in DM.…”