swertiamarin and Obesity

Obesity is a risk factor for many metabolic diseases. Efficient therapeutic strategies are urgently needed. Swertiamarin (STM) prevents obesity and the associated insulin resistance and inflammation. However, the therapeutic effects of STM on preexisting obesity remain unclear. Therefore, in this study we aim to investigate the effects of STM on energy expenditure and fat browning in mice with preexisting obesity. C57BL/6J mice are fed with a high-fat diet (HFD) for 8 weeks to induce obesity and then gavaged (or not) with STM for 10 weeks. The whole-body energy metabolism of mice is examined by indirect calorimetry. The results show that after 10 weeks of treatment, STM markedly prevents HFD-induced weight gain, chronic inflammation, insulin resistance, and hepatic steatosis. STM promotes oxygen consumption and energy expenditure. The level of uncoupling protein 1 is enhanced in the brown and white adipose tissues of STM-treated mice. STM increases the phosphorylation of AMP-activated protein kinase and the expressions of genes involved in fat oxidation, reducing fat deposition in skeletal muscles. Meanwhile, STM does not affect the intestinal microbiotic composition. Overall, STM supplementation may serve as a potential therapy for obesity.

Topics: Adipose Tissue; Adipose Tissue, Brown; Animals; Diet, High-Fat; Energy Metabolism; Inflammation; Insulin Resistance; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Oxidative Stress

Obesity is characterized by low-grade chronic inflammation, which underlies insulin resistance and non-alcoholic fatty liver disease (NAFLD). Swertiamarin is a secoiridoid glycoside that has been reported to ameliorate diabetes and NAFLD in animal models. However, the effects of swertiamarin on obesity-related inflammation and insulin resistance have not been fully elucidated. Thus, this study investigated the effects of swertiamarin on inflammation and insulin resistance in high-fat diet (HFD)-induced obese mice. C57BL/6 mice were fed a HFD or HFD containing swertiamarin for 8 weeks. Obesity-induced insulin resistance and inflammation were assessed in the epididymal white adipose tissue (eWAT) and livers of the mice. Swertiamarin attenuated HFD-induced weight gain, glucose intolerance, oxidative stress, and insulin resistance, and enhanced insulin signalling in mice. Compared to HFD-fed mice, the swertiamarin-treated mice exhibited increased lipolysis and reduced adipocyte hypertrophy and macrophage infiltration in eWAT. Moreover, swertiamarin alleviated HFD-mediated hepatic steatosis and inflammation by suppressing activation of the p38 MAPK and NF-κB pathways within the eWAT and liver of obese mice. In conclusion, supplementation with swertiamarin attenuated weight gain and hepatic steatosis, and alleviated obesity-associated inflammation and insulin resistance, in obese mice.

Topics: Animals; Chronic Disease; Diet, High-Fat; Dietary Supplements; Inflammation; Insulin Resistance; Iridoid Glucosides; Male; Mice; Mice, Inbred C57BL; Obesity; Pyrones

Natural compounds are important resources for drug discovery. Using Caenorhabditis elegans (C. elegans) models, we screened active natural compounds with lipid lowering effects. Swertiamarin was found as a potent candidate to reduce lipid content in C. elegans. Using RNAi screening, we were able to demonstrate that kat-1 (ketoacyl thiolase-1) is necessary for the lipid lowering effect of swertiamarin. Furthermore, the activity of swertiamarin was verified in high fat diet induced obese mice. Consistent with the results in C. elegans, swertiamarin ameliorated high fat diet induced lipid deposition and hyperlipidemia. These results indicate that swertiamarin exerts lipid-lowering effects through kat-1 regulation and could serve as a possible therapeutic option to improve hyperlipidemia induced comorbidities.

Topics: Acetyl-CoA C-Acyltransferase; Animals; Animals, Genetically Modified; Caenorhabditis elegans; Diet, High-Fat; Dose-Response Relationship, Drug; Iridoid Glucosides; Lipid Accumulation Product; Male; Mice; Mice, Inbred C57BL; Obesity; Pyrones; Swertia