Increased adipose catecholamine levels and protection from obesity with loss of Allograft Inflammatory Factor-1

Author:

Chinnasamy Prameladevi,Casimiro IsabelORCID,Riascos-Bernal Dario F.,Venkatesh Shreeganesh,Parikh Dippal,Maira AlishbaORCID,Srinivasan Aparna,Zheng Wei,Tarabra Elena,Zong Haihong,Jayakumar Smitha,Jeganathan Venkatesh,Pradan Kith,Aleman Jose O.ORCID,Singh RajatORCID,Nandi Sayan,Pessin Jeffrey E.,Sibinga Nicholas E. S.ORCID

Abstract

AbstractRecent studies implicate macrophages in regulation of thermogenic, sympathetic neuron-mediated norepinephrine (NE) signaling in adipose tissues, but understanding of such non-classical macrophage activities is incomplete. Here we show that male mice lacking the allograft inflammatory factor-1 (AIF1) protein resist high fat diet (HFD)-induced obesity and hyperglycemia. We link this phenotype to higher adipose NE levels that stem from decreased monoamine oxidase A (MAOA) expression and NE clearance by AIF1-deficient macrophages, and find through reciprocal bone marrow transplantation that donor Aif1-/- vs WT genotype confers the obesity phenotype in mice. Interestingly, human sequence variants near the AIF1 locus associate with obesity and diabetes; in adipose samples from participants with obesity, we observe direct correlation of AIF1 and MAOA transcript levels. These findings identify AIF1 as a regulator of MAOA expression in macrophages and catecholamine activity in adipose tissues – limiting energy expenditure and promoting energy storage – and suggest how it might contribute to human obesity.

Funder

American Heart Association

U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences

U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute

Doris Duke Fund to Retain Clinical Scientists

U.S. Department of Health & Human Services | NIH | NIH Blueprint for Neuroscience Research

U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke

U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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