Calcium signalling in hepatic metabolism: Health and diseases

The flexibility between the wide array of hepatic functions relies on calcium (Ca²⁺) signalling. Indeed, Ca²⁺ is implicated in the control of many intracellular functions as well as intercellular communication. Thus, hepatocytes adapt their Ca²⁺ signalling depending on their nutritional and hormonal environment, leading to opposite cellular functions, such as glucose storage or synthesis. Interestingly, hepatic metabolic diseases, such as obesity, type 2 diabetes and non-alcoholic fatty liver diseases, are associated with impaired Ca²⁺ signalling. Here, we present the hepatocytes' toolkit for Ca²⁺ signalling, complete with regulation systems and signalling pathways activated by nutrients and hormones. We further discuss the current knowledge on the molecular mechanisms leading to alterations of Ca²⁺ signalling in hepatic metabolic diseases, and review the literature on the clinical impact of Ca²⁺-targeting therapeutics.