Lipid droplets, the Holy Grail of hepatic stellate cells: In health and hepatic fibrosis

Abstract

Lipid droplets (LDs) are distinct morphological markers of hepatic stellate cells (HSCs). They are composed of a core of predominantly retinyl esters and triacylglycerols surrounded by a phospholipid layer; the latter harbors perilipins 2, 3, and 5, which help control LD lipolysis. Electron microscopy distinguishes between Types I and II LDs. Type I LDs are surrounded by acid phosphatase-positive lysosomes, which likely digest LDs. LD count and retinoid concentration are modulated by vitamin A intake. Alcohol consumption depletes hepatic retinoids and HSC LDs, with concomitant transformation of HSCs to fibrogenic myofibroblast-like cells. LD loss and accompanying HSC activation occur in HSC cell culture models. Loss of LDs is a consequence of and not a prerequisite for HSC activation. LDs are endowed with enzymes for synthesizing retinyl esters and triacylglycerols as well as neutral lipases and lysosomal acid lipase for breaking down LDs. HSCs have two distinct metabolic LD pools: an "original" pool in quiescent HSCs and a "new" pool emerging in HSC activation; this two-pool model provides a platform for analyzing LD dynamics in HSC activation. Besides lipolysis, LDs are degraded by lipophagy; however, the coordination between and relative contributions of these two pathways to LD removal are unclear. While induction of autophagy accelerates LD loss in quiescent HSCs and promotes HSC activation, blocking autophagy impairs LD degradation and inhibits HSC activation and fibrosis. This article is a critique of five decades of investigations into the morphology, molecular structure, synthesis, and degradation of LDs associated with HSC activation and fibrosis.

Soybean polyenylphosphatidylcholine (PPC) is beneficial in liver and extrahepatic tissue injury: An update in experimental research

“…HSCs, previously called Ito cells, fat‐storing cells or lipocytes, are marked by large number of cytoplasmic lipid droplets (Mak et al, 2023). They reside in the space of Disse and make up 20% of the non‐parenchymal cells of the liver (Figure 4).…”

“…LX‐2 cells were activated with TGF‐β1. DLPC—prepared in liposomes—downregulated α‐SMA protein levels in activated LX‐2 cells but had little effects on the number of lipid droplets—morphological markers of the quiescent phenotype (Mak et al, 2023) and amounts of collagen staining. In comparison, similar treatment of LX‐2 cells with PPC increased the number of lipid droplets, decreased α‐SMA expression and diminished amounts of collagens.…”

From anatomy to immunity in the gastrointestinal system

“…While deposition of fat within hepatocytes is pathological, a prominent hallmark of HSC in healthy livers is their cytoplasmic accumulation of lipid droplets and their large storages of vitamin A (Friedman, 2010). The first article of the section (Mak, Wu, & Cheng, 2022) provides a comprehensive review of HSC lipid droplet dynamics and its relationship with HSC activation and liver disease, examining key pathways involved in lipid droplet formation and breakdown both in health and under pathological conditions. From analysis of the existing evidence, Mak et al show that lipid droplet dynamics is tightly linked to HSC activation and suggest that understanding the nature of the relationship and the mechanisms involved may inform efforts to therapeutically manage the progression of liver fibrosis to cirrhosis.…”