Depicting the Landscape of Adipose Tissue-Specific Macrophages and Their Immunometabolic Signatures during Obesity

Korf, Hannelie; Boesch, Markus; Feio-Azevedo, Rita; Smets, Lena; Vandecasteele, Roselien; Merwe, Schalk van der

doi:10.20900/immunometab20200001

Cited by 7 publications

(5 citation statements)

References 75 publications

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“…Macrophages exhibit both organ- and niche-specific gene expression and function 5 , 39 so we asked if these AIF1-mediated effects on MAOA expression in BMMs extended to macrophages in adipose tissues. Compared to controls, RNA extracted from intact tissues had mildly lower Maoa expression levels in BAT and iWAT of Aif1 −/− mice fed with either CD or HFD, while reduced Aldh1/2 was seen only in BAT and iWAT of HFD-fed mice (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2023

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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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Section: Resultsmentioning

confidence: 99%

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

et al. 2023

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“…Blocking the tra cking of in ammatory monocytes into adipose tissue protected mice from obese-associated in ammation and insulin resistance (Arkan et al, 2005, Weisberg et al, 2006). In addition, recent studies have shown that macrophages in adipose tissue can be divided into many subsets in detail, such as sympathetic neuron-associated macrophages (SAMs), lipid-associated macrophages(LAMs), metabolically activated macrophages (MMe), possessing their own cellular metabolic status and functional characteristics in obesity (Korf et al, 2020). In the aspect of lymphocytes, there were increased amounts of CD4 T cells and CD8 T cells in both abdominal subcutaneous and visceral adipose tissues in obese people, accompanied by increased secretion of in ammatory cytokines such as IL-10 secreted by CD4 T cells (Yang et al, 2010, Winer et al, 2009.…”

Section: Discussionmentioning

confidence: 99%

Analysis of gene expression and immune infiltration in white adipose tissue of patients with obesity: bioinformatics analysis and meta-analysis

Liu,

Ren,

et al. 2024

Preprint

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Background The physiological and pathological process of obesity involves inflammation and immunity. The alterations in the number and function of immune cells may have an effect on systemic inflammation and homeostasis. This study aimed to explore the different biological processes and immune infiltration landscape in obesity. Methods Nine obesity-related datasets were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs)in adipose tissues were identified by “limma” R package or GEO2R and then Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Meanwhile, we conducted the immune infiltration analysis with gene expression data and Meta-analysis was performed based on the results of immune infiltration. Finally, we selected hub genes and tried to find out the connection between hub genes and immune infiltration. Results 46 common DEGs were identified, among which the up-regulated genes were involved in biological processes such as the regulation of hemopoiesis, leukocyte differentiation, activation and migration, cell adhesion, cytokine secretion, and interactions. Immune infiltration analysis showed that the percentages of monocytes and macrophages were increased in obesity, while there was no significant difference in neutrophils. The obese patients had a higher proportion of CD4 T cells, induced regulatory T (iTreg) cells, T follicular helper (Tfh) cells, T helper 2 (Th2) cells, T regulatory type 1 (Tr1) cells, and natural killer (NK) cells, and lower levels of CD8 T cells, B cells, CD8 naive cells, exhausted T (Tex) cells, and γδ T cells compared with the controls. PTPRC、ITGAX、CD86、MMP9、ITGB2、CCR1、TLR8、CCL19、SPP1、TREM2 were identified as hub genes. Conclusion In obesity, genes related to immunity and inflammation are upregulated in adipose tissue, and the function and abundance of immune cells are changed. There are more monocytes and macrophages in obese people than those in non-obese individuals, and there are also differences in lymphocytes and their subsets.

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“…Recent advances in single cell and nuclei RNA sequencing approaches greatly improved our understanding of cellular maladaptation's in AT dysfunction and outdated the historical notion that only two macrophage subpopulations (M1 as pro-inflammatory and M2 as anti-inflammatory macrophages) exist 19,20 . In contrast, AT compromises a plethora of different macrophage subtypes, which flexibly adapt to different metabolic challenges [20][21][22] thereby dictating AT remodelling. Thus, it is essential to unravel weight lossinduced changes in the composition of AT to identify the relevant cell types as well as the intracellular mechanisms and intercellular communications that maintain an obesogenic memory in AT.…”

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confidence: 99%

Adipocyte p53 coordinates the response to intermittent fasting by regulating adipose tissue immune cell landscape

Reinisch,

Michenthaler,

Sulaj

et al. 2024

Nat Commun

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In obesity, sustained adipose tissue (AT) inflammation constitutes a cellular memory that limits the effectiveness of weight loss interventions. Yet, the impact of fasting regimens on the regulation of AT immune infiltration is still elusive. Here we show that intermittent fasting (IF) exacerbates the lipid-associated macrophage (LAM) inflammatory phenotype of visceral AT in obese mice. Importantly, this increase in LAM abundance is strongly p53 dependent and partly mediated by p53-driven adipocyte apoptosis. Adipocyte-specific deletion of p53 prevents LAM accumulation during IF, increases the catabolic state of adipocytes, and enhances systemic metabolic flexibility and insulin sensitivity. Finally, in cohorts of obese/diabetic patients, we describe a p53 polymorphism that links to efficacy of a fasting-mimicking diet and that the expression of p53 and TREM2 in AT negatively correlates with maintaining weight loss after bariatric surgery. Overall, our results demonstrate that p53 signalling in adipocytes dictates LAM accumulation in AT under IF and modulates fasting effectiveness in mice and humans.

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Depicting the Landscape of Adipose Tissue-Specific Macrophages and Their Immunometabolic Signatures during Obesity

Cited by 7 publications

References 75 publications

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

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

Analysis of gene expression and immune infiltration in white adipose tissue of patients with obesity: bioinformatics analysis and meta-analysis

Adipocyte p53 coordinates the response to intermittent fasting by regulating adipose tissue immune cell landscape

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