bergamottin and Disease-Models--Animal

Osteoporosis is one of the most common bone disorders that seriously affect the health and life quality of elderly individuals. Reduced osteoblast differentiation and bone formation lead to changes in bone volume and microarchitecture, leaving the bones vulnerable to fracture. Bergamottin (BM) is a natural compound derived from various citrus fruits and possesses multiple biological activities including anti-adipogenesis function. This study aimed to evaluate the effects of BM on osteoblast differentiation and its potential anti-osteoporosis capacity, as well as to explore the underlying mechanism. We demonstrated that BM, as a positive regulator for osteogenesis, significantly promoted osteoblast differentiation and bone formation. Mechanically, BM activated the Wnt/β-catenin signaling pathway and promoted the nuclear translocation of β-catenin. In addition, BM dramatically upregulated the expression of β-catenin, enhanced the transcriptional activation of T cell factor 7 (TCF7), and increased the expression of Runt-related transcription factor 2 (Runx2). Taken together, this study revealed that BM enhanced osteoblast differentiation and attenuated ovariectomy (OVX)-induced bone loss, possessing the potential to be developed into a food ingredient or supplement for preventing osteoporosis.

Topics: Animals; Cell Proliferation; Cells, Cultured; Citrus; Disease Models, Animal; Female; Furocoumarins; Humans; Mice; Osteoblasts; Osteogenesis; Osteoporosis, Postmenopausal; Ovariectomy; Wnt Signaling Pathway

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.

Topics: 3T3-L1 Cells; Adipogenesis; AMP-Activated Protein Kinases; Animals; Body Weight; CCAAT-Enhancer-Binding Protein-alpha; Cell Differentiation; Citrus paradisi; Depression, Chemical; Diet, High-Fat; Disease Models, Animal; Furocoumarins; Gene Expression; Lipolysis; Mice; Obesity; Phytotherapy; PPAR gamma; Weight Gain