Abstract
The potential biological activities of Viburnum stellato-tomentosum (VS), a plant mainly found in Costa Rica, have yet to be reported. Supplementation of VS extract for 17 weeks significantly decreased body weight gain, fat weight, fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglyceride levels in high-fat diet (HFD)-fed C57BL/6J mice. The molecular mechanisms underlying the anti-obesity and glucose-lowering effects of VS extract were investigated. VS extract suppressed adipocyte hypertrophy by regulating lipogenesis-related CCAAT/enhancer-binding protein α (C/EBPα) and insulin sensitivity-related peroxisome proliferator-activated receptor γ (Pparg) expression in adipose tissue (AT) and hepatic steatosis by inhibiting C/EBPα and lipid transport-related fatty acid binding protein 4 (FABP4) expression. VS extract enhanced muscular fatty acid β-oxidation-related AMP-activated protein kinase (AMPK) and PPARα expression with increasing Pparg levels. Furthermore, VS extract contained a much higher content of amentoflavone (AMF) (29.4 mg/g extract) compared to that in other Viburnum species. AMF administration decreased Cebpa and Fabp4 levels in the AT and liver, as well as improved insulin signaling-related insulin receptor substrate 1 (Irs1) and glucose transporter 1 (Glut1) levels in the muscle of HFD-fed mice. This study elucidated the in vivo molecular mechanisms of AMF for the first time. Therefore, VS extract effectively diminished obesity and hyperglycemia by suppressing C/EBPα-mediated lipogenesis in the AT and liver, enhancing PPARα-mediated fatty acid β-oxidation in muscle, and PPARγ-mediated insulin sensitivity in AT and muscle.
Highlights
Obesity is a state of excessive body fat caused by a chronic imbalance between energy intake and energy expenditure, which results in an increased risk of related comorbidities, including insulin resistance and type 2 diabetes mellitus (T2DM) [1]
The mRNA level of Adiponectin, which is an adipocytokine and an important mediator of insulin action by adipose Pparg [13], was significantly increased in the High-fat diets (HFD)+Viburnum stellato-tomentosum (VS) group. These findings indicate that the anti-obesity and glucose-lowering effects of VS may be due to the inhibition of HFD-induced adipocyte hypertrophy by suppressing adipocyte differentiation, accompanied by enhanced insulin sensitivity
Supplementation with VS extract upregulated the mRNA levels of insulin signaling-related genes, including insulin receptor substrate 1 (Irs1) and glucose transporter 1 (Glut1), while the Irs2 and glucose transporter 4 (Glut4) levels were not changed. These results indicate that VS extract may improve muscular fatty acid β-oxidation and insulin sensitivity
Summary
Obesity is a state of excessive body fat caused by a chronic imbalance between energy intake and energy expenditure, which results in an increased risk of related comorbidities, including insulin resistance and type 2 diabetes mellitus (T2DM) [1]. High-fat diets (HFD), such as Western diets, are characterized by overnutrition, leading to weight gain and obesity due to the presence of excess body fat. Insulin resistance (IR), caused by obesity and T2DM, results in poor insulin function in glucose uptake, metabolism, and storage. These functional defects may impair insulin signaling in insulin-sensitive tissues, including the skeletal muscle, liver, and adipose tissue [3]
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