Abstract

Obesity is a public health problem characterized by increased body weight due to abnormal adipose tissue expansion. Bioactive compound consumption from the diet or intake of dietary supplements is one of the possible ways to control obesity. Natural products with adipogenesis-regulating potential act as obesity treatments. We evaluated the synergistic antiangiogenesis, antiadipogenic and antilipogenic efficacy of standardized rebaudioside A, sativoside, and theasaponin E1 formulations (RASE1) in vitro in human umbilical vein endothelial cells (HUVECs), 3T3-L1 preadipocytes respectively, and in vivo using a high-fat and carbohydrate diet-induced obesity mouse model. Orlistat was used as a positive control, while untreated cells and animals were normal controls (NCs). Adipose tissue, liver, and blood were analyzed after dissection. Extracted stevia compounds and green tea seed saponin E1 exhibited pronounced antiobesity effects when combined. RASE1 inhibited HUVEC proliferation and tube formation by suppressing VEGFR2, NF-κB, PIK3, and-catenin beta-1 expression levels. RASE1 inhibited 3T3-L1 adipocyte differentiation and lipid accumulation by downregulating adipogenesis- and lipogenesis-promoting genes. RASE1 oral administration reduced mouse body and body fat pad weight and blood cholesterol, TG, ALT, AST, glucose, insulin, and adipokine levels. RASE1 suppressed adipogenic and lipid metabolism gene expression in mouse adipose and liver tissues and enhanced AMP-activated protein kinase levels in liver and adipose tissues and in serum adiponectin. RASE1 suppressed the NF-κB pathway and proinflammatory cytokines IL-10, IL-6, and TNF-α levels in mice which involve inflammation and progression of obesity. The overall results indicate RASE1 is a potential therapeutic formulation and functional food for treating or preventing obesity and inflammation.

Highlights

  • Obesity is defined as having a body mass index of ≥30 kg/m2 and is a major and complex metabolic disorder characterized by high body fat accumulation

  • The present study evaluated the effect of standardized green tea seed extract, saponin E1, and extracted stevia compound supplementation on adipocyte differentiation, angiogenesis, and body weight gain in HFD and HCD mice using biochemical markers to elucidate the molecular mechanism underlying such an effect

  • The results showed that RASE1 regulates PI3K/AKT and ERK pathways through VEGF expression. These results provide a molecular basis for understanding green tea seed extract saponins and stevia extract compounds in combination (RASE1) and antihyperlipidemic and fat-pad lowering effects

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Summary

Introduction

Obesity is defined as having a body mass index of ≥30 kg/m2 and is a major and complex metabolic disorder characterized by high body fat accumulation. Obesity is associated with type II diabetes mellitus, hypertension, coronary heart disease, fatty liver disease, and different types of cancer [1, 2]. Expansion of adipose tissue due to an imbalance between energy intake and expenditure results in obesity. This excess energy is stored in adipose cells, thereby enlarging or BioMed Research International increasing cell numbers (hypertrophy and hyperplasia, respectively) [3]. With over 2.1 billion cases being reported, obesity remains a continuous global epidemic accounting for approximately 5% of all deaths [4,5,6]. Obesity has been reported to lead to cognitive dysfunction, depression, and emotional trauma, resulting in a poor quality of life [4, 7]

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