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

Author

Listed:
  • Suneng Fu

    (and Nutrition, Harvard School of Public Health)

  • Ling Yang

    (and Nutrition, Harvard School of Public Health)

  • Ping Li

    (and Nutrition, Harvard School of Public Health)

  • Oliver Hofmann

    (Harvard School of Public Health)

  • Lee Dicker

    (Harvard School of Public Health)

  • Winston Hide

    (Harvard School of Public Health)

  • Xihong Lin

    (Harvard School of Public Health)

  • Steven M. Watkins

    (Lipomics Technologies Inc)

  • Alexander R. Ivanov

    (and Nutrition, Harvard School of Public Health)

  • Gökhan S. Hotamisligil

    (and Nutrition, Harvard School of Public Health
    Broad Institute of Harvard and MIT)

Abstract

Lipid metabolism in obesity The function of the endoplasmic reticulum (ER) changes during obesity: in the liver, ER-associated protein synthesis slows down, and genes involved in lipid metabolism are switched on. ER stress is an important factor in obesity, insulin resistance and type 2 diabetes. A possible mechanism for this link has now been identified. Perturbation of fatty acid and lipid metabolism in the ER inhibits the activity of SERCA, the main ER calcium importer. Changing the lipid composition or increasing the amount of SERCA in the ER is shown to relieve the stress and improve glucose homeostasis in vivo.

Suggested Citation

  • Suneng Fu & Ling Yang & Ping Li & Oliver Hofmann & Lee Dicker & Winston Hide & Xihong Lin & Steven M. Watkins & Alexander R. Ivanov & Gökhan S. Hotamisligil, 2011. "Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity," Nature, Nature, vol. 473(7348), pages 528-531, May.
    • Handle: RePEc:nat:nature:v:473:y:2011:i:7348:d:10.1038_nature09968
    DOI: 10.1038/nature09968
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    Cited by:

    1. Kasparas Petkevicius & Henrik Palmgren & Matthew S. Glover & Andrea Ahnmark & Anne-Christine Andréasson & Katja Madeyski-Bengtson & Hiroki Kawana & Erik L. Allman & Delaney Kaper & Martin Uhrbom & Lis, 2022. "TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Shiyan Liu & Mutian Chen & Yichang Wang & Yuqing Lei & Ting Huang & Yabin Zhang & Sin Man Lam & Huihui Li & Shiqian Qi & Jia Geng & Kefeng Lu, 2023. "The ER calcium channel Csg2 integrates sphingolipid metabolism with autophagy," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Güneş Parlakgül & Song Pang & Leonardo L. Artico & Nina Min & Erika Cagampan & Reyna Villa & Renata L. S. Goncalves & Grace Yankun Lee & C. Shan Xu & Gökhan S. Hotamışlıgil & Ana Paula Arruda, 2024. "Spatial mapping of hepatic ER and mitochondria architecture reveals zonated remodeling in fasting and obesity," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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