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

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

Research output: Contribution to journalArticlepeer-review

Abstract

Recent 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.

Original languageEnglish (US)
Article number38
JournalNature communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • General
  • Physics and Astronomy(all)

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