Playing Jekyll and Hyde—The Dual Role of Lipids in Fatty Liver Disease

Abstract

Lipids play Jekyll and Hyde in the liver. On the one hand, the lipid-laden status of hepatic stellate cells is a hallmark of healthy liver. On the other hand, the opposite is true for lipid-laden hepatocytes—they obstruct liver function. Neglected lipid accumulation in hepatocytes can progress into hepatic fibrosis, a condition induced by the activation of stellate cells. In their resting state, these cells store substantial quantities of fat-soluble vitamin A (retinyl esters) in large lipid droplets. During activation, these lipid organelles are gradually degraded. Hence, treatment of fatty liver disease is treading a tightrope—unsophisticated targeting of hepatic lipid accumulation might trigger problematic side effects on stellate cells. Therefore, it is of great importance to gain more insight into the highly dynamic lipid metabolism of hepatocytes and stellate cells in both quiescent and activated states. In this review, part of the special issue entitled “Cellular and Molecular Mechanisms underlying the Pathogenesis of Hepatic Fibrosis 2020”, we discuss current and highly versatile aspects of neutral lipid metabolism in the pathogenesis of non-alcoholic fatty liver disease (NAFLD).

A Creb3-Like Transcription Factor Coordinates ER Function upon Food Intake to Regulate Lipid Metabolism

“…Changing the levels of this translocon and the supporting ER sorting machinery thus affects the ER protein repertoire, whichin turnchanges the storage and secretion of proteins and lipids. Alterations in the repertoire of these proteins also contribute to ER stress and the lipid accumulation, as is often observed in metabolic diseases (Molenaar et al, 2020).…”

Silmitasertib, a casein kinase 2 inhibitor, induces massive lipid droplet accumulation and nonapoptotic cell death in head and neck cancer cells

“…Autophagy has recently been shown to be involved in lipid catabolism 22 . We subsequently investigated the presence of autophagic flux by inspecting LC3‐I, LC3‐II, and p62 expression in lysates from SCCHN cells treated with CX‐4945.…”

Special Issue on “Cellular and Molecular Mechanisms Underlying the Pathogenesis of Hepatic Fibrosis II”

“…Most articles in this Special Issue focus on aspects of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), which are terms for conditions caused by excess hepatic fat. The complexity of lipid diversity and dynamics during diseases associated with surplus fat buildups is illustrated by Molenaar and coworkers [ 13 ]. Their review provides expert knowledge on mechanisms by which nutritional overload from exogenous sources and the endogenous overproduction of lipids leads to parenchymal fat accumulation.…”