Hepatic stellate cells retain the capacity to synthesize retinyl esters and to store neutral lipids in small lipid droplets in the absence of LRAT

Ajat, Mokrish; Molenaar, Martijn R.; Brouwers, Jos F.; Vaandrager, Arie B.; Houweling, Martin; Helms, J. Bernd

doi:10.1016/j.bbalip.2016.10.013

Cited by 30 publications

(50 citation statements)

References 52 publications

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“…To study this in more detail, we took advantage of the RE metabolism in HSCs. We previously showed that retinol is generated from hydrolysis of endogenous REs and is available for re-synthesis of REs in either the preexisting (LRAT-mediated) or dynamic pool (DGAT1-mediated) of LDs (8). Indeed, after the addition of deuterated fatty acids to the cell culture medium, we not only observed an incorporation of D4-labeled palmitate into TAGs (Fig.…”

Section: Rat Hscs Have An Active Autophagy Pathway That Is Required Fmentioning

confidence: 71%

“…Upon activation, the percentage of retinyl palmitate species drops, reflecting RE synthesis by DGAT1 in the dynamic LD pool. If lalistat inhibits the breakdown of REs from the preexisting LD pool, then it is expected that lalistat also prevents the remodeling of the RE pool during activation as reflected in the change in retinyl ester species distribution (8). Indeed, at day 1 the predominantly retinyl ester is palmitate (84 Ϯ 3%) in rat HSCs, whereas after activation on day 7 a more diverse species distribution was observed (Fig.…”

Section: Rat Hscs Have An Active Autophagy Pathway That Is Required Fmentioning

confidence: 98%

“…In quiescent HSCs, retinyl palmitate is the predominant RE species (Ͼ80%) in preexisting LDs (8). Upon activation, the percentage of retinyl palmitate species drops, reflecting RE synthesis by DGAT1 in the dynamic LD pool.…”

Section: Rat Hscs Have An Active Autophagy Pathway That Is Required Fmentioning

confidence: 99%

“…We previously suggested that HSCs contain two pools of LDs, a preexisting and a dynamic pool of LDs. The preexisting LD pool is characterized by a larger average size of the LD diameter, the presence of REs, and the involvement of its synthesizing enzyme LRAT (8,9). The dynamic LDs were shown to be smaller than preexisting LDs and have a dynamic lipid metabolism, with new TAG synthesis and hydrolysis at relatively high rates (9).…”

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confidence: 99%

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Lysosome-mediated degradation of a distinct pool of lipid droplets during hepatic stellate cell activation

Tuohetahuntila

Molenaar

Spee

et al. 2017

Journal of Biological Chemistry

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Section: Rat Hscs Have An Active Autophagy Pathway That Is Required Fmentioning

confidence: 71%

Section: Rat Hscs Have An Active Autophagy Pathway That Is Required Fmentioning

confidence: 98%

Section: Rat Hscs Have An Active Autophagy Pathway That Is Required Fmentioning

confidence: 99%

mentioning

confidence: 99%

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Lysosome-mediated degradation of a distinct pool of lipid droplets during hepatic stellate cell activation

Tuohetahuntila

Molenaar

Spee

et al. 2017

Journal of Biological Chemistry

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“…Both cell lines also express matrix remodeling factors, including MMP-2, TIMP-1, TIMP-2, MT1-MMP, and multiple neuronal genes. Both cell lines express mRNA for procollagen 1a1 and HSP47, and they retain key features of HSC such as accumulating retinol and converting it to retinyl ester [26,[108][109][110].…”

Section: Lx-1 and Lx-2mentioning

confidence: 99%

Human hepatic stellate cell isolation and characterization

et al. 2017

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The hepatic stellate cells (HSCs) localize at the space of Disse in the liver and have multiple functions. They are identified as the major contributor to hepatic fibrosis. Significant understanding of HSCs has been achieved using rodent models and isolated murine HSCs; as well as investigating human liver tissues and human HSCs. There is growing interest and need of translating rodent study findings to human HSCs and human liver diseases. However, species-related differences impose challenges on the translational research. In this review, we focus on the current information on human HSCs isolation methods, human HSCs markers, and established human HSC cell lines.

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The lipid droplet lipidome

Wölk,

Fedorova

2024

FEBS Letters

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Lipid droplets (LDs) are intracellular organelles with a hydrophobic core formed by neutral lipids surrounded by a phospholipid monolayer harboring a variety of regulatory and enzymatically active proteins. Over the last few decades, our understanding of LD biology has evolved significantly. Nowadays, LDs are appreciated not just as passive energy storage units, but rather as active players in the regulation of lipid metabolism and quality control machineries. To fulfill their functions in controlling cellular metabolic states, LDs need to be highly dynamic and responsive organelles. A large body of evidence supports a dynamic nature of the LD proteome and its contact sites with other organelles. However, much less is known about the lipidome of LDs. Numerous examples clearly indicate the intrinsic link between LD lipids and proteins, calling for a deeper characterization of the LD lipidome in various physiological and pathological settings. Here, we reviewed the current state of knowledge in the field of the LD lipidome, providing a brief overview of the lipid classes and their molecular species present within the neutral core and phospholipid monolayer.

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Hepatic stellate cells retain the capacity to synthesize retinyl esters and to store neutral lipids in small lipid droplets in the absence of LRAT

Cited by 30 publications

References 52 publications

Lysosome-mediated degradation of a distinct pool of lipid droplets during hepatic stellate cell activation

Lysosome-mediated degradation of a distinct pool of lipid droplets during hepatic stellate cell activation

Human hepatic stellate cell isolation and characterization

The lipid droplet lipidome

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