The expressions of IL TNF and IL major
The expressions of IL6, TNFα, and IL1β, major pro-inflammatory cytokines secreted during tissue damage , are decreased in the kidney of AM095 treated mice compared with STZ-vehicle group. However, the GSK1838705A of the inducer of microphage infiltration, MCP1, involved in early stage of inflammatory response was lowest expressed in STZ-vehicle group . These results suggest that STZ-vehicle group may be further progressed in pathological stage compared with other treatment groups. The expression of fibrotic factors is regulated by inflammatory cytokines . We found that the expression of TGFβ1 and fibronectin was higher in the diabetic condition and was lowered by AM095 treatment. Consistent with these data, the expressions of fibrotic factors, such as collagen and TIMP-1, were also reduced in the kidney of AM095-treated mice. Taken together, these data indicated that the decrease in inflammatory cytokine expression by AM095 treatment may contribute to the reduction of expressions of fibrotic factors.
Conclusion The following are the supplementary data related to this article.
Funding This study was supported by grants from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF2016R1A2B2013347) and Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HI14C1135).
Conflict of interest
Introduction The rapid increase in the prevalence of overweight and obesity is becoming an important health problem. Overweight and obesity may cause several metabolic complications, including type 2 diabetes mellitus, hyperlipidemia, high cholesterol, hypertension as well as coronary artery disease . Prevention and treatment of obesity will benefit the treatment of these related diseases. Despite years of progress in medicine, there are no highly effective pharmacological treatments for obesity. Thus, great effort is needed to investigate the molecular mechanisms controlling obesity and to develop novel pharmacological strategies to treat obesity and its complications. The natural compound celastrol, a pentacyclic triterpene extracted from the roots of Tripterygium Wilfordi plant (a traditional Chinese herb), exerts various bioactivities including anti-diabetic and anti-obese effects . Recent studies from animal models of diabetes and obesity illustrate that celastrol could alleviate obesity and insulin resistance . Celastrol has been reported to have anti-obesity effects via inhibition of adipogenesis and metabolic disorder to increase energy expenditure and expression of mitochondrial genes in mice fed with high fat diet . Celastrol improves nonalcoholic fatty liver disease (NAFLD) by reducing lipid synthesis and elevating the anti-oxidative and anti-inflammatory status in mice fed with high fat diet . In vitro, celastrol increased adipocyte differentiation and lipolysis by regulating peroxisome proliferator-activated receptor gamma 2 (PPARγ2) and CCAAT/enhancer-binding protein alpha (C/EBPα) signaling in 3T3-L1 adipocytes . Besides, treatment with celastrol increases the expression of heat shock transcription factor 1 (HSF1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in skeletal muscle and adipocytes of diet-induced obese mice , which can promote thermogenesis and the remodeling of white adipose tissues. Moreover, the previous work verified that celastrol treatment reduced body weight gain and food intake in both high fat-fed obese in diabetes (db/db) and leptin-deficient (ob/ob) mice by inhibiting ER stress and increasing STAT3-dependent leptin signaling . Nevertheless, the detailed molecular basis of celastrol on food intake and obesity has not been sufficiently explored. Therefore, in this study we used diet-induced obese mice to determine the effect of celastrol on food intake and obesity and the underlying mechanisms.