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Whether store-operated Ca2+ entry is altered in steatotic hepatocytes and the mechanisms involved were investigated. Lipid accumulation in\u00a0vitro was induced in cultured liver cells by amiodarone or palmitate and in\u00a0vivo in hepatocytes isolated from obese Zucker rats. Rates of Ca2+ entry and release were substantially reduced in lipid-loaded cells. Inhibition of Ca2+ entry was associated with reduced hormone-initiated intracellular Ca2+ signalling and enhanced lipid accumulation. Impaired Ca2+ entry was not associated with altered expression of stromal interaction molecule 1 (STIM1) or Orai1. Inhibition of protein kinase C (PKC) reversed the impairment of Ca2+ entry in lipid-loaded cells. It is concluded that steatosis leads to a substantial inhibition of SOCE through a PKC-dependent mechanism. This enhances lipid accumulation by positive feedback and may contribute to the development of NASH and insulin resistance.<\/jats:p>","DOI":"10.1042\/bj20140881","type":"journal-article","created":{"date-parts":[[2014,11,25]],"date-time":"2014-11-25T09:33:45Z","timestamp":1416908025000},"page":"379-390","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":90,"title":["Steatosis inhibits liver cell store-operated Ca2+ entry and reduces ER Ca2+ through a protein kinase C-dependent mechanism"],"prefix":"10.1042","volume":"466","author":[{"given":"Claire\u00a0H.","family":"Wilson","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, School of Medicine, Flinders University, Adelaide, South Australia 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun\u00fcs\u00a0S.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, School of Medicine, Flinders University, Adelaide, South Australia 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Scrimgeour","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, The University of Adelaide, Adelaide, South Australia 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyce\u00a0M.","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, School of Medicine, Flinders University, Adelaide, South Australia 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, School of Medicine, Flinders University, Adelaide, South Australia 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George\u00a0A.","family":"Tallis","sequence":"additional","affiliation":[{"name":"Medical Biochemistry, SA Pathology, Finders Medical Centre, Bedford Park, South Australia 5042, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grigori\u00a0Y.","family":"Rychkov","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, The University of Adelaide, Adelaide, South Australia 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg\u00a0J.","family":"Barritt","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, School of Medicine, Flinders University, Adelaide, South Australia 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2015,2,20]]},"reference":[{"key":"2021112216143488700_B1","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.cmet.2009.03.011","article-title":"As a matter of fat","volume":"10","author":"Brookheart","year":"2009","journal-title":"Cell Metab."},{"key":"2021112216143488700_B2","doi-asserted-by":"publisher","first-page":"G697","DOI":"10.1152\/ajpgi.00426.2010","article-title":"Obesity, diabetes mellitus, and liver fibrosis","volume":"300","author":"Chiang","year":"2011","journal-title":"Am. 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