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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:BackgroundParkinson's disease (PD) is a neurodegenerative disorder with a significant immune component, as demonstrated by changes in immune biomarkers in patients' biofluids. However, which specific cells are responsible for those changes is unclear because most immune biomarkers can be produced by various cell types.ObjectivesThe aim of this study was to explore monocyte involvement in PD.MethodsWe investigated the monocyte-specific biomarker sCD163, the soluble form of the receptor CD163, in cerebrospinal fluid (CSF) and serum in two experiments, and compared it with other biomarkers and clinical data. Potential connections between CD163 and alpha-synuclein were studied in vitro.ResultsCSF-sCD163 increased in late-stage PD and correlated with the PD biomarkers alpha-synuclein, Tau, and phosphorylated Tau, whereas it inversely correlated with the patients' cognitive scores, supporting monocyte involvement in neurodegeneration and cognition in PD. Serum-sCD163 increased only in female patients, suggesting a sex-distinctive monocyte response. CSF-sCD163 also correlated with molecules associated with adaptive and innate immune system activation and with immune cell recruitment to the brain. Serum-sCD163 correlated with proinflammatory cytokines and acute-phase proteins, suggesting a relation to chronic systemic inflammation. Our in vitro study showed that alpha-synuclein activates macrophages and induces shedding of sCD163, which in turn enhances alpha-synuclein uptake by myeloid cells, potentially participating in its clearance.ConclusionsOur data present sCD163 as a potential cognition-related biomarker in PD and suggest a role for monocytes in both peripheral and brain immune responses. This may be directly related to alpha-synuclein's proinflammatory capacity but could also have consequences for alpha-synuclein processing. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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

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

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