Profilin-1 haploinsufficiency protects against obesity-associated glucose intolerance and preserves adipose tissue immune homeostasis.

Abstract

Metabolic inflammation may contribute to the pathogenesis of obesity and its comorbidities, including type 2 diabetes and cardiovascular disease. Previously, we showed that the actin-binding protein profilin-1 (pfn) plays a role in atherogenesis because pfn heterozygote mice (PfnHet) exhibited a significant reduction in atherosclerotic lesion burden and vascular inflammation. In the current study, we tested whether pfn haploinsufficiency would also limit diet-induced adipose tissue inflammation and insulin resistance (IR). First, we found that a high-fat diet (HFD) upregulated pfn expression in epididymal and subcutaneous white adipose tissue (WAT) but not in the liver or muscle of C57BL/6 mice compared with normal chow. Pfn expression in WAT correlated with F4/80, an established marker for mature macrophages. Of note, HFD elevated pfn protein levels in both stromal vascular cells and adipocytes of WAT. We also found that PfnHet were significantly protected from HFD-induced glucose intolerance observed in pfn wild-type mice. With HFD, PfnHet displayed blunted expression of systemic and WAT proinflammatory cytokines and decreased accumulation of adipose tissue macrophages, which were also preferentially biased toward an M2-like phenotype; this correlated with preserved frequency of regulatory T cells. Taken together, the findings indicate that pfn haploinsufficiency protects against diet-induced IR and inflammation by modulating WAT immune homeostasis.

• Authors: Giulio R Romeo, Munkyong Pae, Delphine Eberlé, Jongsoon Lee, Steven E Shoelson
• Journal: Diabetes (Diabetes) Vol. 62 Issue 11 Pg. 3718-26 (Nov 2013) ISSN: 1939-327X [Electronic] United States
• PMID: 23884883 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Differentiation
• Profilins
• STAT3 Transcription Factor
• Stat3 protein, mouse
• monocyte-macrophage differentiation antigen

Topics

• Adipose Tissue, White (immunology, pathology)
• Animals
• Antigens, Differentiation (biosynthesis)
• Diet, High-Fat
• Glucose Intolerance (genetics)
• Haploinsufficiency
• Homeostasis
• Inflammation (immunology)
• Insulin Resistance (physiology)
• Macrophages (immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Obesity (genetics)
• Profilins (biosynthesis, genetics)
• STAT3 Transcription Factor (metabolism)
• Subcutaneous Fat (immunology, metabolism)