TY - JOUR
T1 - Increased adipose catecholamine levels and protection from obesity with loss of Allograft Inflammatory Factor-1
AU - Chinnasamy, Prameladevi
AU - Casimiro, Isabel
AU - Riascos-Bernal, Dario F.
AU - Venkatesh, Shreeganesh
AU - Parikh, Dippal
AU - Maira, Alishba
AU - Srinivasan, Aparna
AU - Zheng, Wei
AU - Tarabra, Elena
AU - Zong, Haihong
AU - Jayakumar, Smitha
AU - Jeganathan, Venkatesh
AU - Pradan, Kith
AU - Aleman, Jose O.
AU - Singh, Rajat
AU - Nandi, Sayan
AU - Pessin, Jeffrey E.
AU - Sibinga, Nicholas E.S.
N1 - Funding Information:
We thank Victor Schuster, Anne Bresnick, and Richard Stanley for their advice and suggestions. We also thank the personnel of the following core facilities at the Albert Einstein College of Medicine: the Animal Physiology Core for performing metabolic cage studies (Licheng Wu and Zhiping Wu), the Epigenomics Facility for the performance of the Illumina sequencing and library construction, the Computational Genomics Core for data analysis, and the Flow Cytometry facility for assistance with the flow cytometric experiments. We thank the Vanderbilt University Neurochemistry Core for biogenic amine measurement, and Ye Zhang and Mariko Bennett for help with the BrainRNA-seq database. This work was supported by an American Heart Association Predoctoral Fellowship 15PRE25000005 to P.C., NIH grant T32GM007491 to I.C., NIH grant T32HL144456 to A.M., American Heart Association Career Development Award 19CDA34660217 to D.F.R-B, NIH grants R21NS116480 to S.N. and N.E.S.S, R01HL128066 to N.E.S.S, and a pilot grant to N.E.S.S. from the Einstein-Mount Sinai Diabetes Research Center (NIH P30DK020541). J.O.A. was funded by the Doris Duke Fund to Retain Clinical Scientists at New York University Langone Health.
Funding Information:
We thank Victor Schuster, Anne Bresnick, and Richard Stanley for their advice and suggestions. We also thank the personnel of the following core facilities at the Albert Einstein College of Medicine: the Animal Physiology Core for performing metabolic cage studies (Licheng Wu and Zhiping Wu), the Epigenomics Facility for the performance of the Illumina sequencing and library construction, the Computational Genomics Core for data analysis, and the Flow Cytometry facility for assistance with the flow cytometric experiments. We thank the Vanderbilt University Neurochemistry Core for biogenic amine measurement, and Ye Zhang and Mariko Bennett for help with the BrainRNA-seq database. This work was supported by an American Heart Association Predoctoral Fellowship 15PRE25000005 to P.C., NIH grant T32GM007491 to I.C., NIH grant T32HL144456 to A.M., American Heart Association Career Development Award 19CDA34660217 to D.F.R-B, NIH grants R21NS116480 to S.N. and N.E.S.S, R01HL128066 to N.E.S.S, and a pilot grant to N.E.S.S. from the Einstein-Mount Sinai Diabetes Research Center (NIH P30DK020541). J.O.A. was funded by the Doris Duke Fund to Retain Clinical Scientists at New York University Langone Health.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-35683-7
DO - 10.1038/s41467-022-35683-7
M3 - Article
C2 - 36596796
AN - SCOPUS:85145428387
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 38
ER -
