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

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.

SUBMITTER: Chinnasamy P

PROVIDER: S-EPMC9810600 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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

Chinnasamy Prameladevi P Casimiro Isabel I Riascos-Bernal Dario F DF Venkatesh Shreeganesh S Parikh Dippal D Maira Alishba A Srinivasan Aparna A Zheng Wei W Tarabra Elena E Zong Haihong H Jayakumar Smitha S Jeganathan Venkatesh V Pradan Kith K Aleman Jose O JO Singh Rajat R Nandi Sayan S Pessin Jeffrey E JE Sibinga Nicholas E S NES

Nature communications 20230103 1

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 clearanc ...[more]

PMID: 36596796

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Project description:Heat shock response is an essential cellular stress response. Dysregulation of various heat shock proteins (HSPs), within the heat shock response (HSR) pathway, play a vital role in this host-defense mechanism contributing to obesity-induced insulin resistance and type 2 diabetes (T2D). Previously, we have reported changes in the expression levels of several HSPs such as HSP40, HSP60, HSP70, and HSP90 in obese compared with lean individuals. DNAJC27 is a member of the HSP40 protein family that was previously identified as a body mass index (BMI) associated locus in genome-wide association (GWAS) studies. However, not much is known about the changes in DNAJC27 expression levels in obesity and T2D. In the present study, we aimed at understanding changes in DNAJC27 expression levels in plasma, peripheral blood mononuclear cells (PBMCs) and adipose tissue in association with obesity and T2D. A total of 277 individuals enrolled including 160 non-diabetic (96 non-obese and 64 obese) and 117 T2D (45 non-obese and 72 obese) individuals. Plasma level of DNAJC27 was significantly higher in obese individuals (6.28 ± 0.64 ng/mL) compared with non-obese individuals (4.8 ± 0.45 ng/mL) with P = 0.043. Dividing the population based on diabetes status showed that there was a significant increase in the plasma level of DNAJC27 in obese (6.90 ± 1.3 ng/mL) compared with non-obese individuals (3.81 ± 0.43 ng/mL) (P = 0.033) in the non-diabetic group. Similarly, DNAJC27 expression level was also higher in PBMCs and adipose tissue of obese individuals. DNAJC27 was found to be associated with leptin and resistin, adipokines known to be dysregulated in obesity, that stimulate inflammatory processes leading to metabolic disorders. In conclusion, our data show that DNAJC27 is elevated in obese and T2D individuals and was positively associated with obesity biomarkers such as leptin and resistin suggesting that this protein may play a role in the pathophysiology of these disorders.

Dataset Information

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

Publications

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

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