Abstract
We previously reported the potential anti-obesity effects of the water extract of Hydrangea serrata (Thunb.) Ser. leaves (WHS) in high-fat diet-induced obese mice. As an extension of our previous study, we investigated the anti-adipogenic and anti-obesity effects of WHS and its underlying molecular mechanisms in 3T3-L1 preadipocytes and genetically obese db/db mice. WHS attenuated the gene expression of adipogenic transcription factors, CCAAT/enhancer binding protein (C/EBP)α, peroxisome proliferator-activated receptor (PPAR)γ, and sterol regulatory element binding protein (SREBP)-1. Moreover, WHS inhibited the mitotic clonal expansion of preadipocytes by inducing G1 cell cycle arrest. Oral administration of WHS alleviated body weight gain and body fat accumulation in vivo. In addition, adipocyte hypertrophy and liver steatosis were ameliorated by WHS treatment. WHS reduced C/EBPα, PPARγ, and SREBP-1 expression and activated AMPKα phosphorylation in both white adipose tissue (WAT) and liver tissue. WHS also mildly upregulated the expression of thermogenic proteins, including uncoupling protein-1, PPARs, PPARγ coactivator-1α, and sirtuin-1, in brown adipose tissue (BAT). Furthermore, WHS altered the gut microbiota composition to resemble that of wild-type mice. Taken together, our findings suggest that WHS could alleviate adiposity by inhibiting adipogenesis in WAT and the liver and modulating the gut microbiota.
Highlights
Obesity is a notable health problem worldwide, which can lead to several diseases including type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD), cardiovascular disease (CVD), stroke, dyslipidemia, and various types of cancer [1]
These results indicated that WHS suppresses adipocyte differentiation by inhibiting Cebpα, Pparγ, and Srebp-1 mRNA expression and acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and fatty acid-binding protein 4 (FABP4) protein expression, and regulating the AMPK and Akt/mammalian target of rapamycin (mTOR) pathways
WHS markedly reversed the reduced phosphorylation of AMPKα. These results demonstrated that WHS could inhibit adipocyte hypertrophy and adipogenesis by activating AMPKα and inhibiting C/EBPα, PPARγ, and sterol regulatory element binding protein (SREBP)-1 in the subcutaneous fat of db/db mice
Summary
Obesity is a notable health problem worldwide, which can lead to several diseases including type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD), cardiovascular disease (CVD), stroke, dyslipidemia, and various types of cancer [1]. It is mainly caused by an imbalance between energy intake and expenditure, resulting from high-calorie food intake and decreased physical activity. The growth of WAT is mediated by two mechanisms, hyperplasia and hypertrophy, which signify the formation of new adipocytes from precursor cells and an increase in the size of mature adipocytes, respectively [4] Regulating both the size and number of adipocytes is a key strategy for inhibiting adipogenesis and obesity
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