Calcium Signaling As a Therapeutic Target for Liver Steatosis

Trends Endocrinol Metab. 2019 Apr;30(4):270-281. doi: 10.1016/j.tem.2019.02.005. Epub 2019 Mar 5.


Hepatic steatosis, the first step in nonalcoholic fatty liver disease (NAFLD), can arise from various pathophysiological conditions. While lipid metabolism in the liver is normally balanced such that there is no excessive lipid accumulation, when this homeostasis is disrupted lipid droplets (LDs) accumulate in hepatocytes resulting in cellular toxicity. The mechanisms underlying this accumulation and the subsequent hepatocellular damage are multifactorial and poorly understood, with the result that there are no currently approved treatments for NAFLD. Impaired calcium signaling has recently been identified as a cause of increased endoplasmic reticulum (ER) stress contributing to hepatic lipid accumulation. This review highlights new findings on the role of impaired Ca2+ signaling in the development of steatosis and discusses potential new approaches to NAFLD treatment based on these new insights.

Keywords: NASH; PKC; calcium signaling; fatty liver; steatohepatitis; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium / deficiency*
  • Calcium Signaling*
  • Diabetes Mellitus, Type 2 / etiology*
  • Humans
  • Insulin Resistance*
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / etiology*


  • Calcium