AUTHOR=Kagawa Syota , Tanabe Katsuya , Hiromura Makoto , Ogawa Kakuyou , Koga Takayuki , Maeda Takahiro , Amo-Shiinoki Kikuko , Ochi Hiroyuki , Ichiki Yui , Fukuyama Shogo , Suzuki Saori , Suizu Natsuki , Ohmine Takaaki , Hamachi Sakurako , Tsuneki Hiroshi , Okuya Shigeru , Sasaoka Toshiyasu , Tanizawa Yukio , Nagashima Fumihiro TITLE=Hachimijiogan, a traditional herbal medicine, modulates adipose cell function and ameliorates diet-induced obesity and insulin resistance in mice JOURNAL=Frontiers in Pharmacology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1167934 DOI=10.3389/fphar.2023.1167934 ISSN=1663-9812 ABSTRACT=

Hachimijiogan (HJG) has originally been used to ameliorate a variety of symptoms associated with low ambient temperatures. However, its pharmacological action in metabolic organs remains unclear. We hypothesized that HJG may modulate metabolic function and have a potential therapeutic application to metabolic diseases. To test this hypothesis, we investigated metabolic action of HJG in mice. Male C57BL/6J mice chronically administered with HJG showed a reduction in adipocyte size with increased transcription of beige adipocyte-related genes in subcutaneous white adipose tissue. HJG-mixed high-fat diet (HFD)-fed mice showed alleviation of HFD-induced weight gain, adipocyte hypertrophy, liver steatosis with a significant reduction in circulating leptin and Fibroblast growth factor 21 despite no changes in food intake or oxygen consumption. Feeding an HJG-mixed HFD following 4-weeks of HFD feeding, while a limited effect on body weight, improved insulin sensitivity with a reversal of decreased circulating adiponectin. In addition, HJG improved insulin sensitivity in the leptin-deficient mice without significant effects on body weight. Treatment with n-butanol soluble extracts of HJG potentiated transcription of Uncoupling protein 1 mediated by β3-adrenergic agonism in 3T3L1 adipocytes. These findings provide evidence that HJG modulates adipocyte function and may exert preventive or therapeutic effects against obesity and insulin resistance.