Neuropeptide Y1 receptor in immune cells regulates inflammation and insulin resistance associated with diet-induced obesity
Autor: | Ernie Yulyaningsih, Laurent Pangon, Martijn S. Bijker, Shu Lin, Amanda Sainsbury, Yan C. Shi, Laurence Macia, Herbert Herzog, Fabienne Mackay, Lei Zhang, Amy D. Nguyen, Shane T. Grey |
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Rok vydání: | 2012 |
Předmět: |
medicine.medical_specialty
Genotype Endocrinology Diabetes and Metabolism Inflammation Biology Polymerase Chain Reaction Proinflammatory cytokine Eating Mice Insulin resistance Internal medicine 3T3-L1 Cells Internal Medicine medicine Animals Obesity Chemokine CCL2 Mice Knockout Tumor Necrosis Factor-alpha Monocyte Cell Differentiation medicine.disease Dietary Fats IRS2 IRS1 Receptors Neuropeptide Y Insulin receptor Endocrinology medicine.anatomical_structure biology.protein Tumor necrosis factor alpha Female medicine.symptom Insulin Resistance Obesity Studies |
Zdroj: | Diabetes |
ISSN: | 1939-327X |
Popis: | 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. |
Databáze: | OpenAIRE |
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