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 - 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.
UR - https://www.scopus.com/pages/publications/85145428387
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 -