Intestinal AMPK modulation of microbiota mediates crosstalk with brown fat to control thermogenesis.

Autor:	Zhang E; Shanghai Key Laboratory of Compound Chinese Medicines and The Ministry of Education (MOE) Key Laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.; Department of Diabetes Complications & Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA., Jin L; Department of Diabetes Complications & Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA., Wang Y; Department of Diabetes Complications & Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA., Tu J; Department of Diabetes Complications & Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.; Irell & Manella Graduate School of Biological Science, City of Hope National Medical Center, Duarte, CA, USA., Zheng R; Shanghai Key Laboratory of Compound Chinese Medicines and The Ministry of Education (MOE) Key Laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China., Ding L; Shanghai Key Laboratory of Compound Chinese Medicines and The Ministry of Education (MOE) Key Laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.; Department of Diabetes Complications & Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA., Fang Z; Department of Diabetes Complications & Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA., Fan M; Department of Diabetes Complications & Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA., Al-Abdullah I; Department of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA., Natarajan R; Department of Diabetes Complications & Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA., Ma K; Department of Diabetes Complications & Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA., Wang Z; Shanghai Key Laboratory of Compound Chinese Medicines and The Ministry of Education (MOE) Key Laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China., Riggs AD; Department of Diabetes Complications & Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA., Shuck SC; Department of Diabetes and Cancer Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA., Yang L; Shanghai Key Laboratory of Compound Chinese Medicines and The Ministry of Education (MOE) Key Laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China. yl7@shutcm.edu.cn., Huang W; Department of Diabetes Complications & Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA. whuang@coh.org.; Irell & Manella Graduate School of Biological Science, City of Hope National Medical Center, Duarte, CA, USA. whuang@coh.org.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2022 Mar 03; Vol. 13 (1), pp. 1135. Date of Electronic Publication: 2022 Mar 03.
DOI:	10.1038/s41467-022-28743-5
Abstrakt:	The energy-dissipating capacity of brown adipose tissue through thermogenesis can be targeted to improve energy balance. Mammalian 5'-AMP-activated protein kinase, a key nutrient sensor for maintaining cellular energy status, is a known therapeutic target in Type II diabetes. Despite its well-established roles in regulating glucose metabolism in various tissues, the functions of AMPK in the intestine remain largely unexplored. Here we show that AMPKα1 deficiency in the intestine results in weight gain and impaired glucose tolerance under high fat diet feeding, while metformin administration fails to ameliorate these metabolic disorders in intestinal AMPKα1 knockout mice. Further, AMPKα1 in the intestine communicates with brown adipose tissue to promote thermogenesis. Mechanistically, we uncover a link between intestinal AMPKα1 activation and BAT thermogenic regulation through modulating anti-microbial peptide-controlled gut microbiota and the metabolites. Our findings identify AMPKα1-mediated mechanisms of intestine-BAT communication that may partially underlie the therapeutic effects of metformin. (© 2022. The Author(s).)
Databáze:	MEDLINE
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