Adiponectin downregulates CD163 whose cellular and soluble forms are elevated in obesity

Sporrer, Daniela; Weber, Markus; Wanninger, Josef; Weigert, Johanna; Neumeier, Markus; Stögbauer, Fabian; Lieberer, Evelyn; Bala, Margarita; Kopp, Andrea; Schäffler, Andréas; Buechler, Christa

doi:10.1111/j.1365-2362.2009.02170.x

Cited by 49 publications

(48 citation statements)

References 40 publications

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“…1C). Macrophage CD163 expression appears to be elevated in type 2 diabetes and obesity, and our findings are consistent with a previous report that suggested adiponectin reduces CD163 expression in monocytes (32).…”

Section: Adiponectin Promotes the Alternative Activation Of Human Monsupporting

confidence: 82%

Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages

Lovren¹,

Pan²,

Quan³

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

202

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primes human monocytes into alternative anti-inflammatory M2 macrophages. Am J Physiol Heart Circ Physiol 299: H656 -H663, 2010. First published July 9, 2010; doi:10.1152/ajpheart.00115.2010.-Altered macrophage kinetics is a pivotal mechanism of visceral obesityinduced inflammation and cardiometabolic risk. Because monocytes can differentiate into either proatherogenic M1 macrophages or antiinflammatory M2 macrophages, approaches that limit M1 while promoting M2 differentiation represent a unique therapeutic strategy. We hypothesized that adiponectin may prime human monocytes toward the M2 phenotype. Adiponectin promoted the alternative activation of human monocytes into anti-inflammatory M2 macrophages as opposed to the classically activated M1 phenotype. Adiponectin-treated cells displayed increased M2 markers, including the mannose receptor (MR) and alternative macrophage activation-associated CC chemokine-1. Incubation of M1 macrophages with adiponectin-treated M2-derived culture supernatant resulted in a pronounced inhibition of tumor necrosis factor-␣ and monocyte chemotactic protein-1 secretion. Activation of human monocytes into M2 macrophages by adiponectin was mediated, in addition to AMP-activated protein kinase and peroxisome proliferator-activated receptor (PPAR)-␥, via PPAR-␣. Furthermore, macrophages isolated from adiponectin knockout mice demonstrated diminished levels of M2 markers such as MR, which were restored with adiponectin treatment. We report a novel immunoregulatory mechanism through which adiponectin primes human monocyte differentiation into anti-inflammatory M2 macrophages. Conditions associated with low adiponectin levels, such as visceral obesity and insulin resistance, may promote atherosclerosis, in part through aberrant macrophage kinetics. adiponectin; obesity; macrophage activation ATHEROSCLEROSIS IS REGARDED as a dynamic and progressive disease arising from the combination of abnormal lipid metabolism, endothelial dysfunction, and inflammation (35). A crucial step in this inflammatory process is the infiltration of monocytes into the subendothelial space of large arteries and their differentiation into tissue macrophages, whose activation and function are influenced by the cytokines within the inflammatory milieu of the atherosclerotic lesion.

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Section: Adiponectin Promotes the Alternative Activation Of Human Monsupporting

confidence: 82%

Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages

Lovren¹,

Pan²,

Quan³

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

202

123

View full text Add to dashboard Cite

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“…CD163 mRNA levels are increased in the adipose tissue of obese individuals [27], although a clear association between mRNA levels and sCD163 has not been described. Furthermore, the source of sCD163 may also include other tissue macrophages and blood monocytes known to have increased CD163 expression in diabetes [28].…”

Section: Discussionmentioning

confidence: 99%

Soluble CD163: a biomarker linking macrophages and insulin resistance

et al. 2012

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Aims/hypothesis Soluble CD163 (sCD163) was recently identified as a strong risk marker for developing type 2 diabetes. We hypothesised that sCD163 independently associates with insulin resistance. Methods This cross-sectional study includes 234 participants: 96 with type 2 diabetes, 34 with impaired glucose tolerance (IGT) and 104 with normal glucose tolerance (NGT), matched for sex and BMI. Glucose-lowering medication was paused for 1 week before plasma samples were obtained for determination of sCD163 and other inflammatory and metabolic variables. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-IR).

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“…In addition, adiponectin directly inhibits inflammation, angiogenesis, and tumorigenesis [14][15][16]. All these effects are mediated through the activation of AMP-activated protein kinase which is also the mediator of metformin actions [13,[17][18][19]. Although up-regulation of adiponectin expression and secretion by insulin-sensitising agents, such as thiazolidinediones, has been established [20,21], the role of metformin in the modulation of adiponectin expression and secretion is controversial [2,[22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo Effects of Metformin on Human Adipose Tissue Adiponectin

Zulian

Cancello

Girola³

et al. 2011

Obes Facts

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Objective: The effects of metformin on adiponectin production are controversial and have never been investigated in human adipose tissue. We analysed whether metformin modulates, in vitro and in vivo, gene expression, protein content, and secretion of adiponectin. Methods: For the in vitro study, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) samples from 5 non-diabetic obese patients were collected. For the in vivo investigation, 22 obese patients were randomly assigned to metformin+lifestyle (ML) or placebo+lifestyle (PL) intervention. SAT specimens and blood samples were collected before and after the intervention in both groups. Results: In in vitro experiments, treatment with metformin increased the expression and secretion of adiponectin in SAT, but not in VAT explants. In the in vivo study, a significant increase in adiponectin and a decreased expression of a macrophage activation marker (CD68) were observed only in SAT of the ML group. Conclusion: These results demonstrate that metformin is able to up-regulate adiponectin gene expression, both in vivo and in vitro, and to stimulate adiponectin protein secretion from human SAT in vitro. It could be hypothesised that metformin-induced adiponectin increase within adipose tissue may have an unexpected role in the reduction of local inflammation.

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Adiponectin downregulates CD163 whose cellular and soluble forms are elevated in obesity

Abstract: This study indicates that monocytic CD163 and systemic sCD163 are elevated in T2D and obesity. Adiponectin reduces CD163 in vitro, but additional factors related to obesity like IL-6 may be more relevant in vivo.

Cited by 49 publications

References 40 publications

Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages

Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages

Soluble CD163: a biomarker linking macrophages and insulin resistance

In vitro and in vivo Effects of Metformin on Human Adipose Tissue Adiponectin

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