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

Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE

Original Publication: [London] : Nature Pub. Group

Diabetes Mellitus, Type 2*/metabolism ; Gastrointestinal Microbiome*/physiology ; Metformin*/pharmacology; AMP-Activated Protein Kinases/metabolism ; Adipose Tissue, Brown/metabolism ; Animals ; Diet, High-Fat ; Energy Metabolism ; Intestines ; Mammals/metabolism ; Mice ; Thermogenesis/physiology

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).)

Comment in: Nat Commun. 2022 May 23;13(1):2851. (PMID: 35606343)

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R01 DK124627 United States DK NIDDK NIH HHS; R01 DK081705 United States DK NIDDK NIH HHS; P30 CA033572 United States CA NCI NIH HHS; R01 HL106089 United States HL NHLBI NIH HHS; R56 DK129332 United States DK NIDDK NIH HHS; R01 CA139158 United States CA NCI NIH HHS

9100L32L2N (Metformin)
EC 2.7.11.31 (AMP-Activated Protein Kinases)

Date Created: 20220304 Date Completed: 20220411 Latest Revision: 20230127

20240628

PMC8894485

10.1038/s41467-022-28743-5

35241650