Cajanolactone A, a stilbenoid from Cajanus cajan, inhibits energy intake and lipid synthesis/storage, and promotes energy expenditure in ovariectomized mice

• Published in: Biomedicine & pharmacotherapy 2021-06, Vol.138, p.111491-111491, Article 111491
• Main Authors: Luo, Zhuo-Hui, Huang, Jia-Wen, Meng, Qi-Qi, Wu, Hui-Wen, Yang, Rui-Yi, Fu, Lin-Chun, Hu, Ying-Jie, Shen, Xiao-Ling
• Format: Article
• Language: English
• Subjects: Adipose tissue; Cajanolactone A; Gut; Hypothalamus; Liver; Ovariectomy
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2021.111491

We had reported that cajanolactone A (CLA) from Cajanus cajan dose-dependently inhibited ovariectomy-induced obesity and liver steatosis in mice, showing potential to prevent postmenopausal obesity and fatty liver. In this study, the role of CLA in the regulation of energy and lipid homeostasis was investigated. Ovariectomized mice treated with CLA or vehicle for 12 weeks were performed a 48 h monitoring for energy metabolism and food uptake. After that, hypothalami, perigonadal (pWATs), inguinal (iWATs) and brown (BATs) adipose tissues, livers, sera, and fecal and cecal contents were collected and analyzed. In CLA-treated mice, we observed reduced food uptake; increased energy expenditure; inhibited expression of orexigenic genes (ORX, ORXR2, pMCH and Gal) in the hypothalami, of lipogenic genes (CD36, SREBP-1c, ChREBP, PPARγ) in the livers, and of lipid storage proteins in the WATs (FSP27, MEST and caveolin-1) and livers (FSP27, Plin2 and Plin5); stimulated expression of metabolism-related proteins (pATGL and Echs1) in the adipose tissues and of thermogenic protein (UCP1) in the inguinal WATs; increased BAT content; increased mitochondria in the pWATs and livers; inhibited angiogenesis in the pWATs; and altered gut microbiome diversity with an increased abundance of Bacteroides. CLA prevents ovariectomy-induced obesity and liver steatosis via regulating energy intake and lipid synthesis/storage, promoting UCP1-dependent heat production, and protecting the mitochondrial function of hepatocytes and adipocytes. The improved gut microecology and inhibited angiogenesis may also contribute to the anti-obese activity of CLA. [Display omitted] •The stilbene cajanolactone A protects the ovariectomized mice fed a high-fat diet from obesity and fatty liver through reducing the food uptake and promoting the energy expenditure.•CLA reduces food uptake through downregulating the expression of orexigenic genes in the hypothalamus.•CLA Promotes energy expenditure through protecting the brown and beige adipose tissues and the mitochondria.•Altered gut microecology may contribute to the antiobese effect of CLA.