Hormone-sensitive lipase is a retinyl ester hydrolase in human and rat quiescent hepatic stellate cells

Shajari, Shiva; Saeed, Ali; Smith-Cortinez, Natalia; Heegsma, Janette; Sydor, Svenja; Faber, Klaas Nico

doi:10.1016/j.bbalip.2019.05.012

Cited by 16 publications

(17 citation statements)

References 40 publications

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“…54 Briefly, primary hepatocytes were isolated after 2-step collagenase perfusion (Sigma-Aldrich, St. Louis, MO). 55,56 Cell viability >80% was determined by Trypan blue (Sigma-Aldrich). Primary hepatocytes were used after 4 hours of attachment on collagen-coated plates in William's E (Gibco by Life Technologies; Thermo Fisher Scientific, Bleiswijk, the Netherlands) medium with 10% fetal calf serum, 50-mg/mL gentamycin, and 100-U/mL penicillin/streptomycin/amphotericin B.…”

Section: Isolation and Culture Of Primary Rat Hepatocytes And Hscsmentioning

confidence: 99%

“…Primary rat HSCs were isolated after pronase (Merck, Amsterdam, the Netherlands) and collagenase-P (Roche, Almere, the Netherlands) perfusion and followed by Nycodenz (Axis-ShieldPOC; Oslo, Norway) density gradient centrifugation. 55 Primary hepatocytes and HSCs were exposed to bovine serum albumin-conjugated palmitic acid (0.25 or 0.5 mmol/ L; Sigma-Aldrich), with or without 5-mM retinol (Sigma-Aldrich) for 24-48 hours as previously described. 57 Quantitative Real-Time Reverse-Transcription Polymerase Chain Reaction Quantitative real-time reverse transcription polymerase chain reaction was performed as previously described.…”

Section: Isolation and Culture Of Primary Rat Hepatocytes And Hscsmentioning

confidence: 99%

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Impaired Hepatic Vitamin A Metabolism in NAFLD Mice Leading to Vitamin A Accumulation in Hepatocytes

Saeed

Bartuzi

Heegsma

et al. 2021

Cellular and Molecular Gastroenterology and Hepatology

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Background & Aims Systemic retinol (vitamin A) homeostasis is controlled by the liver, involving close collaboration between hepatocytes and hepatic stellate cells (HSCs). Genetic variants in retinol metabolism ( PNPLA3 and HSD17B13 ) are associated with non-alcoholic fatty liver disease (NAFLD) and disease progression. Still, little mechanistic details are known about hepatic vitamin A metabolism in NAFLD, which may affect carbohydrate and lipid metabolism, inflammation, oxidative stress and the development of fibrosis and cancer, e.g. all risk factors of NAFLD. Methods Here, we analyzed vitamin A metabolism in 2 mouse models of NAFLD; mice fed a high-fat, high-cholesterol (HFC) diet and Leptin ob mutant ( ob/ob ) mice. Results Hepatic retinol and retinol binding protein 4 (RBP4) levels were significantly reduced in both mouse models of NAFLD. In contrast, hepatic retinyl palmitate levels (the vitamin A storage form) were significantly elevated in these mice. Transcriptome analysis revealed a hyperdynamic state of hepatic vitamin A metabolism, with enhanced retinol storage and metabolism (upregulated Lrat, Dgat1, Pnpla3 , Raldh’s and RAR/RXR-target genes) in fatty livers, in conjunction with induced hepatic inflammation (upregulated Cd68 , Tnfα , Nos2 , Il1β, Il-6 ) and fibrosis (upregulated Col1a1 , Acta2 , Tgfβ , Timp1 ). Autofluorescence analyses revealed prominent vitamin A accumulation in hepatocytes rather than HSC in HFC-fed mice. Palmitic acid exposure increased Lrat mRNA levels in primary rat hepatocytes and promoted retinyl palmitate accumulation when co-treated with retinol, which was not detected for similarly-treated primary rat HSCs. Conclusion NAFLD leads to cell type-specific rearrangements in retinol metabolism leading to vitamin A accumulation in hepatocytes. This may promote disease progression and/or affect therapeutic approaches targeting nuclear receptors.

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Section: Isolation and Culture Of Primary Rat Hepatocytes And Hscsmentioning

confidence: 99%

Section: Isolation and Culture Of Primary Rat Hepatocytes And Hscsmentioning

confidence: 99%

Impaired Hepatic Vitamin A Metabolism in NAFLD Mice Leading to Vitamin A Accumulation in Hepatocytes

Saeed

Bartuzi

Heegsma

et al. 2021

Cellular and Molecular Gastroenterology and Hepatology

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“…From the above studies, it was found that the mechanism of PNPLA3 regulating TG was complicated. In other studies, it was also found that PNPLA3 also had retinyl esterase activity and participates in the metabolism of vitamin A in the body 29 , 30 . In addition, Huang et al 17 revealed that PNPLA3 achieves nutritional control through a feed-forward loop, which started from transcriptional upregulation and expands through coordinated inhibition of protein degradation.…”

Section: Physiological Function Of Pnpla3mentioning

confidence: 82%

Research progress, challenges and perspectives on PNPLA3 and its variants in Liver Diseases

Xiang

Wang

et al. 2021

J. Cancer

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The human patatin-like phospholipase domain-containing 3 gene (PNPLA3) is highly expressed in liver and adipose tissue and encodes a transmembrane polypeptide chain containing 481 amino acids. The I148M variant of PNPLA3 is a single nucleotide polymorphism, which is related to a variety of liver and cardiovascular diseases and their complications (such as non-alcoholic fatty liver disease, liver fibrosis, coronary artery disease). This review mainly describes the pathophysiological effects of PNPLA3 and its variants, and their roles in the progression of liver disease and its complications.

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“…Afterward, cells were separated by Nycodenz (Axis-ShieldPOC, Oslo, Norway) gradient centrifugation, as described before. 26 Freshly isolated HSCs were culture-activated to activated HSCs for 7 days. Cells were harvested 4 hours, 1-, 3-, and 7-days after isolation to observe the time-and culture-dependent activation of HSCs in vitro.…”

Section: Cell Culturementioning

confidence: 99%

“…2.6 | RNA isolation, cDNA synthesis, and real-time quantitative PCR Two-step reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed as previously described. 26 Briefly, RNA was isolated from cell cultures using TRIzol reagent according to the supplier's instruction (Thermo Fisher Scientific, Amsterdam, The Netherlands). RNA quality and quantity were determined using a NanoDrop 2000c UV-vis spectrophotometer (Thermo Fisher Scientific).…”

Section: Treatmentsmentioning

confidence: 99%

Collagen release by human hepatic stellate cells requires vitamin C and is efficiently blocked by hydroxylase inhibition

et al. 2020

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Hormone-sensitive lipase is a retinyl ester hydrolase in human and rat quiescent hepatic stellate cells

Cited by 16 publications

References 40 publications

Impaired Hepatic Vitamin A Metabolism in NAFLD Mice Leading to Vitamin A Accumulation in Hepatocytes

Impaired Hepatic Vitamin A Metabolism in NAFLD Mice Leading to Vitamin A Accumulation in Hepatocytes

Research progress, challenges and perspectives on PNPLA3 and its variants in Liver Diseases

Collagen release by human hepatic stellate cells requires vitamin C and is efficiently blocked by hydroxylase inhibition

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