Sweroside ameliorates NAFLD in high-fat diet induced obese mice through the regulation of lipid metabolism and inflammatory response

• Published in: Journal of ethnopharmacology 2020-06, Vol.255, p.112556-112556, Article 112556
• Main Authors: Yang, Qiaoling, Shu, Fangfang, Gong, Junting, Ding, Ping, Cheng, Rongrong, Li, Jinmei, Tong, Renchao, Ding, Lili, Sun, Huajun, Huang, Wendong, Wang, Zhengtao, Yang, Li
• Format: Article
• Language: English
• Subjects: Animals; CD36 Antigens - genetics; CD36 Antigens - metabolism; Diet, High-Fat; Disease Models, Animal; Fibroblast Growth Factors - genetics; Fibroblast Growth Factors - metabolism; Gene Regulatory Networks; HEK293 Cells; Humans; Inflammation; Inflammation Mediators - metabolism; Insulin Resistance; Iridoid Glucosides - pharmacology; Lipid metabolism; Lipid Metabolism - drug effects; Lipid Metabolism - genetics; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Mice, Inbred C57BL; NAFLD; Non-alcoholic Fatty Liver Disease - etiology; Non-alcoholic Fatty Liver Disease - metabolism; Non-alcoholic Fatty Liver Disease - pathology; Non-alcoholic Fatty Liver Disease - prevention & control; Obesity - etiology; Obesity - metabolism; Obesity - physiopathology; Obesity - prevention & control; PPAR alpha - genetics; PPAR alpha - metabolism; PPAR-α; Transcriptome; Weight Gain - drug effects; weroside
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2020.112556

Sweroside, an iridoid derived from Traditional Chinese Medicine, is an active component in Swertia pseudochinensis Hara. Swertia pseudochinensis Hara is first recorded in “Inner Mongolia Chinese Herb Medicine”and is considered as a folk medicine for treating hepatitis in northern China. Aim of the study: This study sought to elucidate the role of sweroside in high fat diet induced obesity and fatty liver by using mouse model and investigated the primary molecular mechanism via transcriptomics analysis. C57BL/6 mice were fed high-fat diet (HFD) for 14 weeks to induce obesity, hyperglycemia, and fatty liver. These mice were subsequently treated with HFD alone or mixed with sweroside (at a daily dosage of 60 mg per kg of BW, 120 mg per kg of BW and 240 mg per kg of BW) for 6 weeks. BW and food intake was monitored weekly. Biochemical and pathological analysis were conducted to investigate the effect of sweroside on NAFLD. RNA-sequence and RT-qPCR analysis were performed to analyze the potential mechanism. The mice treated with sweroside were resistant to HFD-induced body weight gain, insulin resistance and hepatic steatosis. Ingenuity pathway analysis (IPA) demonstrated that hepatic gene networks related to lipid metabolism and inflammatory response were down-regulated in the HFD + sweroside group. PPAR-ɑ was located in the center of the hepatic gene network, and the significantly altered genes were CD36 and FGF21, which are related to hepatic inflammation and lipid metabolism. Consistently, upstream-regulators analysis revealed that the main enriched upstream-regulator was PPAR-ɑ. Our results indicate that sweroside may ameliorate obesity with fatty liver via the regulation of lipid metabolism and inflammatory responses. The beneficial effects of sweroside might be closely associated with the regulation of PPAR-α. [Display omitted] •Sweroside ameliorates the HFD-induce body weight gain, hepatic steatosis and serum lipid levels in DIO mice.•Sweroside improves glucose homeostasis and insulin sensitivity in DIO mice.•Sweroside attenuates HFD-induced hepatic inflammation in DIO mice.•Sweroside improves obesity with fatty liver by regulating the lipid metabolism and inflammatory responses.•The effect of sweroside in regulating inflammatory response and lipid metabolism is closely related with PPAR-α.