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

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 () and Wendong Huang ()
Additional contact information
Eryun Zhang: Shanghai University of Traditional Chinese Medicine
Lihua Jin: City of Hope National Medical Center
Yangmeng Wang: City of Hope National Medical Center
Jui Tu: City of Hope National Medical Center
Ruirong Zheng: Shanghai University of Traditional Chinese Medicine
Lili Ding: Shanghai University of Traditional Chinese Medicine
Zhipeng Fang: City of Hope National Medical Center
Mingjie Fan: City of Hope National Medical Center
Ismail Al-Abdullah: City of Hope National Medical Center
Rama Natarajan: City of Hope National Medical Center
Ke Ma: City of Hope National Medical Center
Zhengtao Wang: Shanghai University of Traditional Chinese Medicine
Arthur D. Riggs: City of Hope National Medical Center
Sarah C. Shuck: City of Hope National Medical Center
Li Yang: Shanghai University of Traditional Chinese Medicine
Wendong Huang: City of Hope National Medical Center

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-28743-5

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