Li Chang, Leng Qingyang, Li Lihua, Hu Fan, Xu Yuejie, Gong Sa, Yang Ying, Zhang Hongli, Li Xiaohua
Department of Endocrinology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China.
Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200030, China.
Endocrinology. 2023 Feb 11;164(4). doi: 10.1210/endocr/bqad035.
Berberine (BBR), which is a compound derived from the Chinese medicinal plant Coptis chinensis, promotes weight loss, but the molecular mechanisms are not well understood. Here, we show that BBR increases the serum level of growth differentiation factor 15 (GDF15), which is a stress response cytokine that can reduce food intake and lower body weight in diet-induced obese (DIO) mice. The body weight and food intake of DIO mice were decreased after BBR treatment, and the weight change was negatively correlated with the serum GDF15 level. Further studies show that BBR induced GDF15 mRNA expression and secretion in the brown adipose tissue (BAT) of DIO mice and primary mouse brown adipocytes. In addition, we found that BBR upregulates GDF15 mRNA expression and secretion by activating the integrated stress response (ISR) in primary mouse brown adipocytes. Overall, our findings show that BBR lowers body weight by inducing GDF15 secretion via the activation of the ISR in BAT.
黄连素（BBR）是一种从中国药用植物黄连中提取的化合物，具有促进体重减轻的作用，但其分子机制尚不清楚。在此，我们发现BBR可提高生长分化因子15（GDF15）的血清水平，GDF15是一种应激反应细胞因子，可减少饮食诱导的肥胖（DIO）小鼠的食物摄入量并降低体重。BBR处理后，DIO小鼠的体重和食物摄入量均下降，且体重变化与血清GDF15水平呈负相关。进一步研究表明，BBR可诱导DIO小鼠棕色脂肪组织（BAT）和原代小鼠棕色脂肪细胞中GDF15 mRNA的表达和分泌。此外，我们发现BBR通过激活原代小鼠棕色脂肪细胞中的综合应激反应（ISR）来上调GDF15 mRNA的表达和分泌。总体而言，我们的研究结果表明，BBR通过激活BAT中的ISR诱导GDF15分泌，从而降低体重。
