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Jiang Gui Fang activated interscapular brown adipose tissue and induced epididymal white adipose tissue browning through the PPAR gamma/SIRT1-PGC1 alpha pathway

作者 Zu, Yu-xin; Lu, Hong-yuan; Liu, Wen-wu; Jiang, Xiao-wen; Huang, Yuan; Li, Xiang; Zhao, Qing-chun; Xu, Zi-hua

期刊 JOURNAL OF ETHNOPHARMACOLOGY , FEB 10 2020,:248

DOI 10.1016/j.jep.2019.112271 PubMed 31586693

摘要 Ethnopharmacological relevance: Gui Zhi Tang, a well-known Chinese herbal formula recorded in the Eastern Han Dynasty, has been widely used to treat exogenous cold for thousands of years. Recent studies have shown that Gui Zhi Tang has the effect of regulating the body temperature. Because of its effect on heat production, protecting vital organs of the body and avoiding damage from the cold environment, Jiang Gui Fang (JG) was obtained from the Department of Traditional Chinese Medicine at the General Hospital of Northern Theatre Command where it has been used clinically for many years and has exhibited favourable efficacy. Based on research on Gui Zhi Tang, the principles of traditional Chinese medicine and survey of a large number of studies, this empirical formula was developed. The composition of JG included Dried ginger, Cassia twig, and Liquorice in Gui Zhi Tang, which play a major role in the treatment of exogenous cold, and combined these components with other Chinese medicines, such as Pueraria, Spatholobus, Acanthopanacis cortex, Evodiae fructus, and Codonopsis pilosula.Aim of the study: To promote the core body temperature and prevent invasion of the major organs from the cold environment, we studied the effect of JG on the core body temperature of mice and then explored its regulation of interscapular brown adipose tissue (iBAT) and epididymal white adipose tissue (eWAT) and the possible mechanism. Finally, we determined the phytochemical composition of JG that plays a role in heat production.Materials and methods: In vivo study, we performed a 4-week treatment of JG in acute cold environment at -20 degrees C and chronic cold exposure at 4 degrees C. The core temperature, adipose tissue weight, serum parameters, and morphological observation of adipocytes, liver and kidney were measured. Then we investigated the expression levels of adipogenic factors, thermogenic factors and lipoprotein. In vitro, we determined the lipid droplet content, ATP content, and the maximum oxygen consumption of mitochondria.Results: JG treatment promoted core temperature, inhibited eWAT weight, protected liver, and reduced glucose and lipids in Kunming (KM) mice. JG also increased the expression of BAT-associated thermogenic factors, including uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1 alpha). The levels of the lipogenic factor peroxisome proliferate-activator receptor gamma (PPAR gamma) and the lipolytic protein hormone-sensitive triglyceride lipase (HSL) in eWAT were elevated. The results of H&E and immunohistochemistry showed that JG significantly reduced the size of iBAT and eWAT and increased the content of UCP1. In vitro, JG reduced the content of lipid droplets and ATP in brown fat cells. The maximum oxygen consumption capacity of mitochondria and the expression levels of UCP1, PGC1 alpha and silent mating type information regulation 2 homologue 1 (SIRT1) were enhanced after JG treatment.Conclusions: In vivo and in vitro studies, the results demonstrated that JG obviously increased the core temperature of mice by activating iBAT and inducing eWAT browning, which proved the mechanism is closely related to the PPAR gamma/SIRT1-PGC1 alpha pathway. In this paper, we will provide a reference for further study of iBAT activation and eWAT browning.

涉及物种 党参 Codonopsis pilosula