Nodakenin represses obesity and its complications via the inhibition of the VLDLR signalling pathway in vivo and in vitro

OBJECTIVES: Nodakenin (NK) is a coumarin glucoside that is found in the roots of Angelicae gigas. A limited number of studies have been conducted on the pharmacological activities of NK. Although NK is an important natural resource having anti‐inflammatory and antioxidant effects, no investigation has been conducted to examine the effects of NK on obesity and obesity‐induced inflammation. MATERIALS AND METHODS: The present study investigated the therapeutic effects of NK treatment on obesity and its complications, and its mechanism of action using differentiated 3T3‐L1 adipocytes and high‐fat diet (HFD)‐induced obese mice. Oil red O staining, western blot assay, qRT‐PCR assay, siRNA transfection, enzyme‐linked immunosorbent assay, H&E staining, immunohistochemistry, molecular docking and immunofluorescence staining were utilized. RESULTS: Treatment with NK demonstrated anti‐adipogenesis effects via the regulation of adipogenic transcription factors and genes associated with triglyceride synthesis in differentiated 3T3‐L1 adipocytes. Compared with the control group, the group administered NK showed a suppression in weight gain, dyslipidaemia and the development of fatty liver in HFD‐induced obese mice. In addition, NK administration inhibited adipogenic differentiation and obesity‐induced inflammation and oxidative stress via the suppression of the VLDLR and MEK/ERK1/2 pathways. This is the first study that has documented the interaction between NK and VLDLR structure. CONCLUSION: These results demonstrate the potential of NK as a natural product‐based therapeutic candidate for the treatment of obesity and its complications by targeting adipogenesis and adipose tissue inflammation‐associated markers.