Monocyte chemoattractant protein 1 in obesity and insulin resistance

TLDR

MCP‑1, like other insulin‑responsive genes such as PAI‑1 and SREBP‑1c, remains sensitive to insulin in insulin‑resistant states, and hyperinsulinemia associated with obesity may drive altered expression of such genes in target tissues. This study identifies monocyte chemoattractant protein 1 (MCP‑1) as an insulin‑responsive gene. Insulin drives MCP‑1 expression and secretion in insulin‑resistant adipocytes and obese mice, where MCP‑1 is overexpressed in white adipose tissue and its elevated levels impair insulin‑stimulated glucose uptake and adipogenic gene expression, suggesting that MCP‑1 contributes to adipocyte dedifferentiation and obesity‑related pathologies such as type II diabetes.

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 ( ob / ob ). 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 , β3-adrenergic receptor, and peroxisome proliferator-activated receptor γ). These results suggest that elevated MCP-1 may induce adipocyte dedifferentiation and contribute to pathologies associated with hyperinsulinemia and obesity, including type II diabetes.