Journal article
Defective Hepatic Autophagy in Obesity Promotes ER Stress and Causes Insulin Resistance
Cell metabolism, Vol.11(6), pp.467-478
06/09/2010
DOI: 10.1016/j.cmet.2010.04.005
PMCID: PMC2881480
PMID: 20519119
Abstract
Autophagy is a homeostatic process involved in the bulk degradation of cytoplasmic components, including damaged organelles and proteins. In both genetic and dietary models of obesity, we observed a severe downregulation of autophagy, particularly in Atg7 expression levels in liver. Suppression of Atg7 both in vitro and in vivo resulted in defective insulin signaling and elevated ER stress. In contrast, restoration of the Atg7 expression in liver resulted in dampened ER stress, enhanced hepatic insulin action, and systemic glucose tolerance in obese mice. The beneficial action of Atg7 restoration in obese mice could be completely prevented by blocking a downstream mediator, Atg5, supporting its dependence on autophagy in regulating insulin action. Our data demonstrate that autophagy is an important regulator of organelle function and insulin signaling and that loss of autophagy is a critical component of defective insulin action seen in obesity.
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► Obesity results in defective hepatic autophagy ► Suppression of Atg7 resulted in elevated ER stress and impaired insulin signaling ► Restoration of Atg7 in obese liver tissue resulted in enhanced insulin action and dampened ER stress ► Regulation of insulin action by Atg7 is autophagy dependent and prevented by inhibiting Atg5
Details
- Title: Subtitle
- Defective Hepatic Autophagy in Obesity Promotes ER Stress and Causes Insulin Resistance
- Creators
- Ling Yang - Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USAPing Li - Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USASuneng Fu - Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USAEdiz S Calay - Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USAGökhan S Hotamisligil - Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA
- Resource Type
- Journal article
- Publication Details
- Cell metabolism, Vol.11(6), pp.467-478
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.cmet.2010.04.005
- PMID
- 20519119
- PMCID
- PMC2881480
- ISSN
- 1550-4131
- eISSN
- 1932-7420
- Language
- English
- Date published
- 06/09/2010
- Academic Unit
- Molecular Physiology and Biophysics; Anatomy and Cell Biology
- Record Identifier
- 9984025590202771
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