PPARgamma activation attenuates T-lymphocyte-dependent inflammation of adipose tissue and development of insulin resistance in obese mice.

Abstract

BACKGROUND:

Inflammation of adipose tissue (AT) has been recently accepted as a first step towards obesity-mediated insulin resistance. We could previously show that mice fed with high fat diet (HFD) develop systemic insulin resistance (IR) and glucose intolerance (GI) associated with CD4-positive T-lymphocyte infiltration into visceral AT. These T-lymphocytes, when enriched in AT, participate in the development of fat tissue inflammation and subsequent recruitment of proinflammatory macrophages. The aim of this work was to elucidate the action of the insulin sensitizing PPARgamma on T-lymphocyte infiltration during development of IR, and comparison of the PPARgamma-mediated anti-inflammatory effects of rosiglitazone and telmisartan in diet-induced obesity model (DIO-model) in mice.

METHODS:

In order to investigate the molecular mechanisms underlying early development of systemic insulin resistance and glucose intolerance male C57BL/6J mice were fed with high fat diet (HFD) for 10-weeks in parallel to the pharmacological intervention with rosiglitazone, telmisartan, or vehicle.

RESULTS:

Both rosiglitazone and telmisartan were able to reduce T-lymphocyte infiltration into AT analyzed by quantitative analysis of the T-cell marker CD3gamma and the chemokine SDF1alpha. Subsequently, both PPARgamma agonists were able to attenuate macrophage infiltration into AT, measured by the reduction of MCP1 and F4/80 expression. In parallel to the reduction of AT-inflammation, ligand-activated PPARgamma improved diet-induced IR and GI.

CONCLUSION:

Together the present study demonstrates a close connection between PPARgamma-mediated anti-inflammation in AT and systemic improvement of glucose metabolism identifying T-lymphocytes as one cellular mediator of PPARgamma´s action.

• Authors: Anna Foryst-Ludwig, Martin Hartge, Markus Clemenz, Christiane Sprang, Katharina Hess, Nikolaus Marx, Thomas Unger, Ulrich Kintscher
• Journal: Cardiovascular diabetology (Cardiovasc Diabetol) Vol. 9 Pg. 64 (Oct 18 2010) ISSN: 1475-2840 [Electronic] England
• PMID: 20955583 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antigens, Differentiation
• Benzimidazoles
• Benzoates
• CD3 Complex
• CD3 antigen, gamma chain
• Chemokine CXCL12
• Cxcl12 protein, mouse
• Dietary Fats
• PPAR gamma
• Thiazolidinediones
• monocyte-macrophage differentiation antigen
• Rosiglitazone
• Telmisartan

Topics

• Abdominal Fat (drug effects, immunology, metabolism)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antigens, Differentiation (metabolism)
• Benzimidazoles (pharmacology)
• Benzoates (pharmacology)
• CD3 Complex (metabolism)
• Chemokine CXCL12 (metabolism)
• Chemotaxis (drug effects)
• Dietary Fats
• Disease Models, Animal
• Inflammation (immunology, metabolism, prevention & control)
• Insulin Resistance
• Lymphocyte Activation (drug effects)
• Macrophages (drug effects, immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Obesity (drug therapy, immunology, metabolism)
• PPAR gamma (agonists, metabolism)
• Rosiglitazone
• T-Lymphocytes (drug effects, immunology)
• Telmisartan
• Thiazolidinediones (pharmacology)
• Time Factors