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Relationship between monocyte/macrophage activation marker soluble CD163 and insulin resistance in obese and normal-weight subjects.

ABSTRACT: The relationship of monocyte/macrophage activation to insulin resistance in obesity is unknown.To investigate a marker of macrophage activation, soluble CD163 (sCD163), in relationship to insulin resistance and metabolic parameters in obese and normal-weight subjects.Ninety-five healthy subjects (65 obese and 30 normal-weight) were studied. Plasma concentrations of sCD163 were assessed, as well as markers of glucose homeostasis, anthropometrics, cytokines and adipokines. The relationships between sCD163 and these parameters were investigated, and multiple regression modelling assessing the contribution of sCD163 to insulin resistance (HOMA-IR) was performed.Soluble CD163 was significantly increased in obese subjects compared with normal-weight controls [974 (657, 1272) ng/ml vs 599 (423, 892)?ng/ml, median (IQR); P < 0·0001]. sCD163 was strongly associated with HOMA-IR (Spearman's ? = 0·37, P = 0·0003) and other metabolic parameters. In multiple regression modelling for log HOMA-IR, sCD163 remained significantly associated (P = 0·005) controlling for known mediators of insulin resistance including age, gender, visceral adiposity and inflammatory markers (model R(2) = 0·54, P < 0·0001). Additional nested multiple regression models for log HOMA-IR showed that sCD163 added more than other adipokines and inflammatory markers to the prediction of HOMA-IR.Monocyte/macrophage activation, as reflected by sCD163 levels, is strongly associated with HOMA-IR in normal-weight and obese subjects after controlling for known mediators of insulin resistance. Moreover, sCD163 adds to standard risk markers for predicting insulin resistance. These data suggest that monocyte/macrophage activation may be an important determinant of insulin resistance in obesity.

SUBMITTER: Zanni MV

PROVIDER: S-EPMC3660104 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Relationship between monocyte/macrophage activation marker soluble CD163 and insulin resistance in obese and normal-weight subjects.

Zanni Markella V MV Burdo Tricia H TH Makimura Hideo H Williams Kenneth C KC Grinspoon Steven K SK

Clinical endocrinology 20120901 3

<h4>Context</h4>The relationship of monocyte/macrophage activation to insulin resistance in obesity is unknown.<h4>Objective</h4>To investigate a marker of macrophage activation, soluble CD163 (sCD163), in relationship to insulin resistance and metabolic parameters in obese and normal-weight subjects.<h4>Design and participants</h4>Ninety-five healthy subjects (65 obese and 30 normal-weight) were studied. Plasma concentrations of sCD163 were assessed, as well as markers of glucose homeostasis, a ...[more]

PMID: 22098563

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Project description:BackgroundIncreasing evidence supports a relationship between obesity and either infertility or subfertility in women. Most previous omics studies were focused on determining if the serum and follicular fluid expression profiles of subjects afflicted with both obesity-related infertility and polycystic ovary syndrome (PCOS) are different than those in normal healthy controls. As granulosa cells (GCs) are essential for oocyte development and fertility, we determined here if the protein expression profiles in the GCs from obese subjects are different than those in their normal-weight counterpart.MethodsGC samples were collected from obese female subjects (n = 14) and normal-weight female subjects (n = 12) who were infertile and underwent in vitro fertilization (IVF) treatment due to tubal pathology. A quantitative approach including tandem mass tag labeling and liquid chromatography tandem mass spectrometry (TMT) was employed to identify differentially expressed proteins. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were then conducted to interrogate the functions and pathways of identified proteins. Clinical, hormonal, and biochemical parameters were also analyzed in both groups.ResultsA total of 228 differentially expressed proteins were noted, including 138 that were upregulated whereas 90 others were downregulated. Significant pathways and GO terms associated with protein expression changes were also identified, especially within the mitochondrial electron transport chain. The levels of free fatty acids in both the serum and follicular fluid of obese subjects were significantly higher than those in matched normal-weight subjects.ConclusionsIn GCs obtained from obese subjects, their mitochondria were damaged and the endoplasmic reticulum stress response was accompanied by dysregulated hormonal synthesis whereas none of these changes occurred in normal-weight subjects. These alterations may be related to the high FFA and TG levels detected in human follicular fluid.

Dataset Information

Relationship between monocyte/macrophage activation marker soluble CD163 and insulin resistance in obese and normal-weight subjects.

Publications

Relationship between monocyte/macrophage activation marker soluble CD163 and insulin resistance in obese and normal-weight subjects.

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