Monocyte chemoattractant protein 1 in obesity and insulin resistance

Abstract

This study identifies monocyte chemoattractant protein 1 (MCP-1) as an insulin-responsive gene. It also shows that insulin induces substantial expression and secretion of MCP-1 both in vitro in insulin-resistant (IR) 3T3-L1 adipocytes and in vivo in IR obese mice (ob͞ob). Thus, MCP-1 resembles other previously described genes (e.g., PAI-1 and SREBP-1c) that remain sensitive to insulin in IR states. The hyperinsulinemia that frequently accompanies obesity and insulin resistance may therefore contribute to the altered expression of these and other genes in insulin target tissues. In vivo studies also demonstrate that MCP-1 is overexpressed in obese mice compared with their lean controls, and that white adipose tissue is a major source of MCP-1. The elevated MCP-1 may alter adipocyte function because addition of MCP-1 to differentiated adipocytes in vitro decreases insulin-stimulated glucose uptake and the expression of several adipogenic genes (LpL, adipsin, GLUT-4, aP2, ␤3-adrenergic receptor, and peroxisome proliferatoractivated receptor ␥). These results suggest that elevated MCP-1 may induce adipocyte dedifferentiation and contribute to pathologies associated with hyperinsulinemia and obesity, including type II diabetes.

Pharmacogenomic assessment of treatment options in gestational diabetes

“…Recent studies show that expression and secretion of MCP-1 is induced by insulin. 31 This is in line with our observation that insulin administration lead to an elevation of both MCP-1 messenger expression and protein level in GDM patients treated with diet and insulin to the level in normal patients. The significance of the decrease of MCP-1 in GDM patients on dietary monotherapy remains to be determined.…”

“…Several studies reported the increase of MCP-1 serum levels in patients with obesity, insulin resistance and Type II diabetes. [31][32][33][34] Surprisingly, GeneCalling showed that MCP-1 mRNA was downregulated in GDM patients on diet therapy compared to normal patients and GDM patient on diet and insulin therapy. We investigated whether this change in gene expression translated to a similar change in serum protein levels for MCP-1.…”

Improved insulin sensitivity and adipose tissue dysregulation after short-term treatment with pioglitazone in non-diabetic, insulin-resistant subjects

“…The adipocyte-secreted MCP-1 was recently demonstrated to be induced by IL-6 and TNFα and to decrease insulin-stimulated glucose uptake as well as the expression of GLUT4, aP2 and PPARγ [49]. Furthermore, MCP-1 and other macrophage-related genes were reduced in ob/ob mice following thiazolidinedione treatment [14].…”

ALOX5AP expression, but not gene haplotypes, is associated with obesity and insulin resistance

“…11 MCP1 is increased in the circulation of obese subjects, is produced by adipose tissue, and decreases glucose uptake in adipocytes. [12][13][14] Both MCP1 and 5LO products recruit leukocytes to sites of inflammation. 15 These data indirectly suggest that ALOX5AP also might play a role in obesity.…”