Calcium Signaling As a Therapeutic Target for Liver Steatosis

Eunüs S Ali; Nikolai Petrovsky

doi:10.1016/j.tem.2019.02.005

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.

Authors

Eunüs S Ali¹, Nikolai Petrovsky²

Affiliations

¹ College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
² College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia; Vaxine Pty Ltd, 11 Walkley Avenue, Warradale, Adelaide, SA, Australia. Electronic address: nikolai.petrovsky@flinders.edu.au.

PMID: 30850262
DOI: 10.1016/j.tem.2019.02.005

Abstract

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*

Substances

Calcium