Ginsenoside Rd Ameliorates High Fat Diet‐Induced Obesity by Enhancing Adaptive Thermogenesis in a cAMP‐Dependent Manner

Abstract

Objective With the discovery of thermogenic adipocytes in humans, it has been hypothesized that enhancing adaptive thermogenesis may improve obesity. Although many studies have found that ginseng can improve obesity, the beneficial effects of ginsenoside Rd on obesity and its mechanisms have not been studied. Methods High‐fat diet‐induced obese mice were used as the study subjects, with intraperitoneal injection of Rd daily at a dose of 15 mg/kg. Body weight and energy metabolism were observed. The effects of Rd on glucose tolerance, insulin sensitivity, and cold tolerance were tested. The expression of genes associated with thermogenesis was analyzed. Finally, the mechanisms by which Rd regulates adaptive thermogenesis were studied. Results Rd ameliorated obesity and insulin resistance. Rd increased cold tolerance through enhancing thermogenic gene expression in brown adipose tissue and increased the browning of white adipose tissue induced by cold stress. Rd increased intracellular cyclic adenosine monophosphate (cAMP) content. Decreasing intracellular cAMP levels by an inhibitor of adenylyl cyclase SQ22536 abolished the promoting effects of Rd on the expression of thermogenic genes. Conclusions Rd improves obesity and insulin resistance. The upregulation of thermogenesis by Rd is dependent on the cAMP/protein kinase A signaling pathway.

Ginsenoside Rd promotes omentin secretion in adipose through TBK1-AMPK to improve mitochondrial biogenesis via WNT5A/Ca2+ pathways in heart failure

“…In this study, TAC, CAL and ISO-induced HF mice models were performed to simulate clinical symptoms of HF [ 28 , 29 ]. Ginsenoside Rd has been studied to reduce insulin resistance and alleviate TAC-induced cardiac hypertrophy [ 30 , 31 ]. In the present study, ginsenoside Rd was found to ameliorate myocardial ischemia injury in TAC, CAL and ISO-induced HF, mainly due to enhancing myocardial contractility and inhibiting cardiac pathological changes.…”

Biotransformation, Pharmacokinetics, and Pharmacological Activities of Ginsenoside Rd Against Multiple Diseases

“…The browning of white adipose tissue induced by cold stress and cAMP levels are increased by ginsenoside Rd. In particular, Rd alleviates obesity and insulin resistance by upregulating thermogenesis through the cAMP/protein kinase A (PKA) signaling pathway ( Yao et al, 2020 ). In fast-food diet-induced non-alcoholic fatty liver disease (NAFLD), fermented ginsenoside Rd with Cordyceps militaris regulates lipid metabolism and the inflammatory response via mTORC1 signaling ( Choi et al, 2019 ).…”

Effect of Panax notoginseng Saponins and Major Anti-Obesity Components on Weight Loss

“…In addition, other studies have found that ginsenosides Rb2, Rg1, and Rg3 induced AMPK phosphorylation, stimulated the expression of UCP1, and increased thermogenesis and mitochondrial gene expression to induce BAT activation and white adipocyte browning Hong et al, 2019;Kim et al, 2020). Ginsenoside Rd enhances thermal gene expression in brown adipose tissue through the PKA signaling pathway and increases browning of white adipose tissue induced by cold exposure (Yao et al, 2020).…”