Intestinal AMPK Modulation of Microbiota Mediates Crosstalk with Brown Fat to Control Thermogenesis

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Mar 4

PMID 35241650

Authors

Eryun Zhang

Lihua Jin

Yangmeng Wang

Jui Tu

Ruirong Zheng

Lili Ding

Zhipeng Fang

Mingjie Fan

Ismail Al-Abdullah

Rama Natarajan

Ke Ma

Zhengtao Wang

Arthur D Riggs

Sarah C Shuck

Li Yang

Wendong Huang

Affiliations

Soon will be listed here.

Abstract

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.

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