Antibiotic Azithromycin inhibits brown/beige fat functionality and promotes obesity in human and rodents

作者：Jian Yu, Xin Chen, Yuanjin Zhang, Xiangdi Cui, Zhe Zhang, Wenxiu Guo, Dongmei Wang, Shengbo Huang, Yanru Chen, Yepeng Hu, Cheng Zhao, Jin Qiu, Yu Li, Meiyao Meng, Mingwei Guo, Fei Shen, Mengdi Zhang, Ben Zhou, Xuejiang Gu, Jiqiu Wang, Xin Wang, Xinran Ma, Lingyan Xu · 发表于：Theranostics · 年份：2022 · DOI：10.7150/thno.63067 · 被引用次数：26 · 研究领域：Adipose Tissue and Metabolism、Adipokines, Inflammation, and Metabolic Diseases、Exercise and Physiological Responses

Obesity, a metabolic disease caused by multiple factors, has become a global health problem. In addition to nutrient intake and sedentary lifestyle, environmental pollutants exposure has been shown to be involved in obesity epidemics. Antibiotics, a new type of environmental pollutant, have been widely used in animal husbandry, aquaculture and microorganism. However, the effects of antibiotics exposure on fat metabolism and metabolic diseases are largely unknown. Methods: We screened major types of antibiotics to examine their effects on the differentiation capacity and thermogenic functionality of brown and beige adipocytes, and found that azithromycin, one major kind of macrolide antibiotics suppressed brown and beige adipocyte functionality. We thus examined azithromycin accretion in adipose tissues of obese patients that correlates with BMI by high performance liquid chromatography-tandem mass spectrometry and systematically explore the influences of azithromycin on adiposity and metabolic performance in mice under high diet. Results: Azithromycin (macrolides) inhibits the mitochondrial and thermogenic gene programs of brown and beige adipocytes, thus disrupting their mitochondrial function and thermogenic response. Consistently, azithromycin treatment are more prone to diet-induced obesity in mice, and this was associated with impaired energy expenditure. Importantly, azithromycin is more accumulated in adipose tissue of obese patients and correlates with BMI and body we...