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      Store-operated Ca 2+ entry (SOCE) controls induction of lipolysis and the transcriptional reprogramming to lipid metabolism

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          SUMMARY

          Ca 2+ signals were reported to control lipid homeostasis but the Ca 2+ channels and pathways involved are largely unknown. Store-operated Ca 2+ entry (SOCE) is a ubiquitous Ca 2+ influx pathway regulated by stromal interaction molecule 1 (STIM1) and STIM2, and by the Ca 2+ channel ORAI1. We show that SOCE-deficient mice accumulate pathological amounts of lipid droplets in liver, heart and skeletal muscle. Cells from patients with loss-of-function mutations in STIM1 or ORAI1 show a similar phenotype, suggesting a cell intrinsic role for SOCE in the regulation of lipid metabolism. SOCE is crucial to induce mobilization of fatty acids from lipid droplets, lipolysis and mitochondrial fatty acid oxidation. SOCE regulates cAMP production and the expression of neutral lipases as well as the transcriptional regulators of lipid metabolism, PGC-1α and PPARα. SOCE-deficient cells upregulate lipophagy that protects them against lipotoxicity. Our data provide evidence for an important role of SOCE in lipid metabolism.

          eTOC

          Calcium signaling is fundamental to many cellular processes and alterations in cellular Ca 2+ homeostasis occur in metabolic disorders. Maus et al delineate the role of store-operated calcium entry (SOCE), an important pathway for increasing intracellular Ca 2+ levels, in lipid metabolism in SOCE-deficient mice and cells from human patients.

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          Author and article information

          Journal
          101233170
          32527
          Cell Metab
          Cell Metab.
          Cell metabolism
          1550-4131
          1932-7420
          5 January 2017
          26 January 2017
          07 March 2017
          07 March 2018
          : 25
          : 3
          : 698-712
          Affiliations
          [1 ]Department of Pathology, New York University School of Medicine, New York, NY, USA
          [2 ]Department of Pediatrics, Zagreb University Hospital Centre and School of Medicine, Croatia
          [3 ]Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA
          [4 ]Department of Medicine, New York University School of Medicine, New York, NY, USA
          [5 ]Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, and Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
          Author notes
          Address Correspondence to: Stefan Feske, MD, Department of Pathology, Experimental Pathology Program, New York University School of Medicine, 550 First Avenue, Smilow 316, New York, NY 10016, Tel: (212) 263-9066, feskes01@ 123456nyumc.org
          [6]

          Current address: Institute of Vegetative Physiology, University of Cologne, Germany.

          Article
          PMC5342942 PMC5342942 5342942 nihpa840452
          10.1016/j.cmet.2016.12.021
          5342942
          28132808
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