Neuropeptide Y1 receptor in immune cells regulates inflammation and insulin resistance associated with diet-induced obesity.

Abstract

Recruitment of activated immune cells into white adipose tissue (WAT) is linked to the development of insulin resistance and obesity, but the mechanism behind this is unclear. Here, we demonstrate that Y1 receptor signaling in immune cells controls inflammation and insulin resistance in obesity. Selective deletion of Y1 receptors in the hematopoietic compartment of mice leads to insulin resistance and inflammation in WAT under high fat-fed conditions. This is accompanied by decreased mRNA expression of the anti-inflammatory marker adiponectin in WAT and an increase of the proinflammatory monocyte chemoattractant protein-1 (MCP-1). In vitro, activated Y1-deficient intraperitoneal macrophages display an increased inflammatory response, with exacerbated secretion of MCP-1 and tumor necrosis factor, whereas addition of neuropeptide Y to wild-type macrophages attenuates the release of these cytokines, this effect being blocked by Y1 but not Y2 receptor antagonism. Importantly, treatment of adipocytes with the supernatant of activated Y1-deficient macrophages causes insulin resistance, as demonstrated by decreased insulin-induced phosphorylation of the insulin receptor and Akt as well as decreased expression of insulin receptor substrate 1. Thus, Y1 signaling in hematopoietic-derived cells such as macrophages is critical for the control of inflammation and insulin resistance in obesity.

• Authors: Laurence Macia, Ernie Yulyaningsih, Laurent Pangon, Amy D Nguyen, Shu Lin, Yan C Shi, Lei Zhang, Martijn Bijker, Shane Grey, Fabienne Mackay, Herbert Herzog, Amanda Sainsbury
• Journal: Diabetes (Diabetes) Vol. 61 Issue 12 Pg. 3228-38 (Dec 2012) ISSN: 1939-327X [Electronic] United States
• PMID: 23011592 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CCL2
• Dietary Fats
• Receptors, Neuropeptide Y
• Tumor Necrosis Factor-alpha
• neuropeptide Y-Y1 receptor

Topics

• 3T3-L1 Cells
• Animals
• Cell Differentiation
• Chemokine CCL2 (genetics, metabolism)
• Dietary Fats (adverse effects)
• Eating (genetics, physiology)
• Female
• Genotype
• Inflammation (genetics, immunology, metabolism)
• Insulin Resistance (genetics, physiology)
• Mice
• Mice, Knockout
• Obesity (etiology, immunology, metabolism)
• Polymerase Chain Reaction
• Receptors, Neuropeptide Y (genetics, metabolism)
• Tumor Necrosis Factor-alpha (genetics, metabolism)