Bergamottin Inhibits Adipogenesis in 3T3-L1 Cells and Weight Regulation in Diet-Induced Obese Mice

Abstract

Obesity is a serious and increasing health problem worldwide, and the inhibition of adipogenesis is considered to be a potential therapeutic target for it. Bergamottin (BGM), a component of grapefruit juice, has been reported to regulate lipolysis. However, the physiological role of BGM in obesity has not been evaluated so far. In the present study, we investigated the effects of BGM on obesity in 3T3-L1 cells and in mice fed a high-fat diet (HFD). BGM inhibited adipogenic differentiation of 3T3-L1 cells along with a significant decrease in the lipid content by downregulating the expression of two critical adipogenic factors, CCAAT enhancer-binding protein-alpha (C/EBP[Formula: see text]) and peroxisome proliferator activated receptor-gamma (PPAR[Formula: see text]). The expressions of target proteins such as adipocyte fatty acid-binding protein (aP2), adiponectin, and resistin were also decreased by BGM. It activated AMP-activated protein kinase (AMPK) by increasing phosphorylation of AMPK and the downstream target acetyl-CoA carboxylase (ACC), indicating that BGM exerted its antiadipogenic effect through AMPK activation. In the HFD-induced obese mouse model, BGM administration significantly reduced the weight and sizes of white adipose tissue as well as the weight gain of mice fed HFD. Moreover, UCP1 and PGC1[Formula: see text] expressions, well-known as brown adipocyte marker genes, were higher in the BGM-treated HFD mice than that in the HFD-induced obese mice. This study suggests that BGM suppress adipogenesis by AMPK activation in vitro and reduces body weight in vivo.

Anti-Diabetic Effect of a Shihunine-Rich Extract of Dendrobium loddigesii on 3T3-L1 Cells and db/db Mice by Up-Regulating AMPK–GLUT4–PPARα

“…Pu et al reported that naringin attenuated the obesity, dyslipidemia, fatty liver, liver dysfunction, and insulin resistance on high-fat diet (HFD)-fed mice, and its protection effect worked by phosphorylating AMPKα and insulin receptor substrate 1 (IRS 1) [41]. Ko et al reported that bergamottin treatment significantly reduced the weight of obese mice by activating AMPK [42]. Ursolic acid is a PPARα activator [43].…”

“…The whole stage of induction took more than a week, and detailed operations of each step have been described in the literature [30]. The fully differentiated 3T3-L1 adipocytes were treated with 1 µM dexamethasone for 48 h, and an insulin-resistant (IR) adipocyte model was then established, and detailed operations have been described in the literature [42].…”

“…The fluorescence intensity values were calculated using Image J Software 1.6 (National Institutes of Health, Bethesda, MD, USA). A much more detailed operating description has been given in the literature [42].…”

5′-hydroxy Auraptene stimulates osteoblast differentiation of bone marrow-derived mesenchymal stem cells via a BMP-dependent mechanism

“…On the other hand, other reports showed the ability of coumarin derivatives including Pteryxin, Scoparone, and esculetin to suppress the adipocyte differentiation of 3T3L1 via antagonizing PPARγ-dependent pathway [28–30]. In addition, Bergamottin showed to inhibit adipogenesis in vitro (in 3 T3-L1 cell line) and in vivo (in high fat mice model) [31] and Isopsoralen was reported to attenuate the adipogenesis of BMSCs in vitro and in vivo [23].…”

Modeling Adipogenesis: Current and Future Perspective

“…Moreover, 3T3-L1 cells have been used extensively to investigate the underlying molecular mechanisms of adipogenesis and to evaluate the potential application of various compounds and nutrients in the treatment of obesity [ 38 ]. For example, compounds such as purpurin [ 39 ], bergamottin [ 40 ] and quercetin [ 41 ] were shown to inhibit adipogenic differentiation in 3T3-L1 cells mainly through downregulating the expression of two adipogenic factors, CCAAT enhancer-binding protein alpha (C/EBPα) and peroxisome proliferator activated receptor-gamma (PPARγ). On the other hand, several obesogenic compounds, such as the methanolic Valerian root extract [ 42 ], oleic acid [ 43 ] and vulpinic acid [ 44 ], have also been studied, in order to dissect the mechanisms of action during the differentiation process of 3T3-L1 cells.…”