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High-Fat Diet-Induced Adipocyte Cell Death Occurs Through a Cyclophilin D Intrinsic Signaling Pathway Independent of Adipose Tissue Inflammation.
- Source :
- Diabetes; Aug2011, Vol. 60 Issue 8, p2134-2143, 10p, 7 Graphs
- Publication Year :
- 2011
-
Abstract
- OBJECTIVE--Previous studies have demonstrated that mice fed a high-fat diet (HFD) develop insulin resistance with proinflammatory macrophage infiltration into white adipose tissue. Concomitantly, adipocytes undergo programmed cell death with the loss of the adipocyte-specific lipid droplet protein perilipin, and the dead/dying adipocytes are surrounded by macrophages that are organized into crown-like structures. This study investigated whether adipocyte cell death provides the driving signal for macrophage inflammation or if inflammation induces adipocyte cell death. RESEARCH DESIGN AND METHODS--Two knockout mouse models were used: granulocyte/monocyte-colony stimulating factor (GM-CSF)-null mice that are protected against HFD-induced adipose tissue inflammation and cyclophilin D (CyP-D)-null mice that are protected against adipocyte cell death. Mice were fed for 4-14 weeks with a 60% HFD, and different markers of cell death and inflammation were analyzed. RESULTS--HFD induced a normal extent of adipocyte cell death in GM-CSF-null mice, despite a marked reduction in adipose tissue inflammation. Similarly, depletion of macrophages by clodronate treatment prevented HFD-induced adipose tissue inflammation without any affect on adipocyte cell death. However, CyP-D deficiency strongly protected adipocytes from HFD-induced cell death, without affecting adipose tissue inflammation. CONCLUSIONS--These data demonstrate that HFD-induced adipocyte cell death is an intrinsic cellular response that is CyP-D dependent but is independent of macrophage infiltration/activation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00121797
- Volume :
- 60
- Issue :
- 8
- Database :
- Complementary Index
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 65359741
- Full Text :
- https://doi.org/10.2337/db10-1411