Flavonoids from Acer okamotoanum Inhibit Adipocyte Differentiation and Promote Lipolysis in the 3T3-L1 Cells

Abstract

Flavonoids, quercitrin, isoquercitrin (IQ), and afzelin, were isolated from ethyl acetate fraction of Acer okamotoanum. We investigated anti-obesity effects and mechanisms of three flavonoids from A. okamotoanum in the differentiated 3T3-L1 cells. The differentiated 3T3-L1 cells increased triglyceride (TG) contents, compared with non-differentiated normal group. However, treatments of three flavonoids from A. okamotoanum decreased TG contents without cytotoxicity. In addition, they showed significant down-regulation of several adipogenic transcription factors, such as γ-cytidine-cytidine-adenosine-adenosine-thymidine/enhancer binding protein -α, -β, and peroxisome proliferator-activated receptor-γ, compared with non-treated control group. Furthermore, treatment of the flavonoids inhibited expressions of lipogenesis-related proteins including fatty acid synthase, adipocyte protein 2, and glucose transporter 4. Moreover, IQ-treated group showed significant up-regulation of lipolysis-related proteins such as adipose triglyceride lipase and hormone-sensitive lipase. In addition, flavonoids significantly activated 5 -adenosine monophosphate-activated protein kinase (AMPK) compared to control group. In particular, IQ showed higher inhibition of TG accumulation by regulation of pathways related with both adipogenesis and lipolysis, than other flavonoids. The present results indicated that three flavonoids of A. okamotoanum showed anti-obesity activity by regulation of adipocyte differentiation, lipolysis, and AMPK signaling, suggesting as an anti-obesity functional agents.Molecules 2020, 25, 1920 2 of 13 activation of hydrolyzing enzymes including hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL), resulting in the production of fatty acids and glycerol [9]. In addition, lipolysis is decreased by over-expression of adipogenic key transcription factors in the adipogenesis [9]. Moreover, phosphorylation of 5 -adenosine monophosphate-activated protein kinase (AMPK) is important for progression of obesity [10]. Therefore, many researchers are focused on treatment of obesity by regulation of AMPK pathway [10,11]. Recently, anti-obesity agents are popular and attracted much attention, but they have several side effects including diarrhea, headache, and gastrointestinal discomfort [12]. Therefore, finding of natural products without side effects for anti-obesity agents by inhibition of adipogenesis and promotion of lipolysis is one of strategies to prevent and treat obesity.Acer okamotoanum is widely distributed in Ulleung-do, Republic of Korea, as one variety of Korean endemic species [13]. A. okamotoanum has been reported to exert some biological activities such as anti-oxidant, anti-hypertension and immune improvement effect [14][15][16]. A. okamotoanum contains biological compounds such as cleomiscosin A and C, gallic acid, and β-amyrin [17]. We previously isolated flavonoids such as quercitrin (QU; quercetin-3-rhamoside), isoquercitrin (IQ; quercetin-3-glucoside), and afzelin (AF; kaempferol-3-rhamoside...

α-Glucosidase Inhibitory Activity and Anti-Adipogenic Effect of Compounds from Dendrobium delacourii

“…Acetyl-CoA carboxylase (ACC) is also responsible for the reduction in fatty acid synthesis [16]; in other words, fat accumulation is inhibited by the activation of ACC [17,18]. Adipogenesis can be inhibited by increasing the phosphorylation of both AMPK and ACC [19]. Protein kinase B (Akt) and glycogen synthase kinase-3 beta (GSK3β) are important protein kinases in adipogenesis.…”

Ribes fasciculatum Ameliorates High-Fat-Diet-Induced Obesity by Elevating Peripheral Thermogenic Signaling

“…Additionally, it reduced UVB-induced apoptosis and exhibited anti-inflammatory properties by suppressing interleukin-6, tumor necrosis factor-α, and prostaglandin E2 in human keratinocytes [ 24 , 26 ]. Another study using 3T3-L1 adipocytes demonstrated that afzelin treatment moderately decreased adipocyte differentiation partly due to the downregulation of genes associated with adipogenesis, including C/EBPα and FAS [ 27 ]. The in vitro experiment we performed using brown adipocytes demonstrated that afzelin treatment (3 and 10 µM) elevated UCP1-luciferase activity without altering preadipocyte and mature adipocyte cell numbers.…”

“…First, we kept the mice in a 4 • C cold room for 2 days. Then, the decrease in mice's body temperatures in a cold room was measured every 0, 0.5, 1, 2, 3,17,19,21,23,25,27,42,44,46, and 48 h by inserting a small-diameter temperature probe into the anus (Thermometer DT-610B, CEM). A depth of >2 cm was inserted into mice in a cold room with a 12 h light/dark cycle and free access to food and water.…”

Special Issue “Flavonoids and Their Disease Prevention and Treatment Potential”: Recent Advances and Future Perspectives

“…Dietary phytochemicals such as flavonoids have been shown to modulate lipid metabolism by increasing basal metabolic rate and thermogenesis [ 18 ]. Kim and colleagues have shown that flavonoids isolated from Acer okamotoanum inhibit adipocyte differentiation and promote lipolysis in the 3T3-L1 adipocytes [ 19 ]. The study also showed significant down-regulation of adipogenic transcription factors, such as γ-cytidine-cytidine-adenosine-adenosine-thymidine/enhancer-binding protein-α, -β, and PPAR-γ.…”