Lipid Analysis Reveals Quiescent and Regenerating Liver‐Specific Populations of Lipid Droplets

Abstract

The mammalian liver, a key organ in lipid homeostasis, can accumulate increased amounts of lipids in certain physiological conditions including liver regeneration. Lipid droplets (LD), the lipid storage organelles in the cytoplasm, are composed of a core of neutral lipids (mainly triacylglycerols and cholesteryl esters) surrounded by a monolayer of phospholipids and cholesterol with associated proteins. It is recognized that LD lipid composition is cell- and environment-specific and enables LD to carry out specific functions, but few descriptive studies aiming to interpret such differences have been published. We characterized eight density fractions of LD isolated from quiescent (control) and regenerating liver after partial hepatectomy, and grouped populations according to their lipid composition. LD from quiescent liver resembled the cholesteryl ester storage LD found in steroidogenic tissues, whereas in the regenerating tissue they were similar to adipocyte LD. Specifically, there were large, light LD with increased triacylglycerol content, the hallmark of liver regeneration. The apparent volume of the dense LD was, however, lower than in the quiescent density-matched populations, concomitant with increased phosphatidylcholine and phosphatidylethanolamine and decreased neutral lipid content. Analysis of the lipid profile of LD populations from quiescent and regenerating tissue leads us to define four physiological LD phenotypes for rat liver.

Impaired liver regeneration in Ldlr−/− mice is associated with an altered hepatic profile of cytokines, growth factors, and lipids

“…In contrast to the aforementioned lipid changes, Ldlr −/− mice did not showed significant differences in the hepatic levels of triglycerides and free fatty acids before or after PH. Considering what has previously been published regarding liver regeneration [10], the hepatic lipid profile of Ldlr −/− mice after PH is compatible with hepatocellular quiescence.…”

“…By contrast, the concentration of cholesterol esters remained elevated in the Ldlr −/− mice without significant changes throughout the regenerative process. These results, together with the observation that high concentration of cholesterol esters are abundant in lipid droplets of quiescent livers, compared with regenerating livers [10], suggest that high levels of cholesterol may favor quiescence in hepatocytes. Another major component of membranes whose concentration is diminished in the liver of Ldlr −/− animals is phosphatidylcholine.…”

“…Besides the steps described above, it is widely recognized that in the early stages of liver regeneration hepatocytes accumulate a significant amount of lipids in cellular structures called lipid droplets, which are mainly composed of triacylglycerol and cholesteryl esters [10, 11]. The functional meaning of this transient steatosis is not well defined as there are conflicting studies on how alteration of the hepatic lipid contents affects the proliferative response [12–17].…”

Structure, Function and Metabolism of Hepatic and Adipose Tissue Lipid Droplets: Implications in Alcoholic Liver Disease

“…A potentially important observation is that the relative distribution of PC or PE modifies the LD size [23]. It has been documented that changes in the phospholipid composition can promote LDs to fuse into supersized structures that appear to be resistant to normal lipolysis [65, 66]. PE is a conical lipid that can increase membrane curvature, thereby promoting membrane fusion [24, 67].…”

Impaired cell proliferation in regenerating liver of 3 β-hydroxysterol Δ14-reductase (TM7SF2) knock-out mice

“…28 The functional meaning of this transient steatosis is not well defined as there are conflicting studies on how alteration of the hepatic lipid content affects the proliferative response. 29 We measured hepatic triglycerides content in WT and Tm7sf2 KO mice.…”