Journal article

Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity

Suneng Fu, Ling Yang, Ping Li, Oliver Hofmann, Lee Dicker, Winston Hide, Xihong Lin, Steven M Watkins, Alexander R Ivanov, Goekhan S Hotamisligil

NATURE | NATURE PUBLISHING GROUP | Published : 2011

Abstract

The endoplasmic reticulum (ER) is the main site of protein and lipid synthesis, membrane biogenesis, xenobiotic detoxification and cellular calcium storage, and perturbation of ER homeostasis leads to stress and the activation of the unfolded protein response. Chronic activation of ER stress has been shown to have an important role in the development of insulin resistance and diabetes in obesity. However, the mechanisms that lead to chronic ER stress in a metabolic context in general, and in obesity in particular, are not understood. Here we comparatively examined the proteomic and lipidomic landscape of hepatic ER purified from lean and obese mice to explore the mechanisms of chronic ER str..

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University of Melbourne Researchers

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Awarded by National Institutes of Health


Awarded by NIH/NIEHS


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Funding Acknowledgements

We thank A. Porter, E. Freeman and R. Davis for technical assistance. The anti-HERP antibody is a gift of Y. Hirabayashi. We thank the members of the G.S.H. laboratory for scientific discussions and critical reading of the manuscript. This work was supported in part by the National Institutes of Health (DK52539 and 1RC4-DK090942) and a research grant from Syndexa Pharmaceuticals to G.S.H. S.F. was supported in part by the NIH/NIEHS postdoctoral training grant (T32ES007155).