The role of alkaline phosphatase in intracellular lipid accumulation in the human hepatocarcinoma cell line, HepG2

Chirambo, George; Niekerk, Chantal van; Crowther, Nigel J.

doi:10.1016/j.yexmp.2017.02.007

Cited by 10 publications

(9 citation statements)

References 42 publications

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“…The MitoBiogenesis In-Cell Enzyme-Linked Immunosorbent Assay Kit (Abcam, Cambridge, UK) uses quantitative immunocytochemistry to measure MT-COX1 and nuclearencoded SDHA protein levels in cultured cells and it was performed following the manufacturer's instructions. 46 Briefly, cells were seeded in a 96-well plate (3 Â 10 5 / well) in triplicate, fixed with 4% paraformaldehyde. and permeabilized through 1Â Triton X-100.…”

Section: Evaluation Of Mt-cox1 Expressionmentioning

confidence: 99%

TM6SF2/PNPLA3/MBOAT7 Loss-of-Function Genetic Variants Impact on NAFLD Development and Progression Both in Patients and in In Vitro Models

Longo

Meroni

Paolini

et al. 2022

Cellular and Molecular Gastroenterology and Hepatology

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Section: Evaluation Of Mt-cox1 Expressionmentioning

confidence: 99%

TM6SF2/PNPLA3/MBOAT7 Loss-of-Function Genetic Variants Impact on NAFLD Development and Progression Both in Patients and in In Vitro Models

Longo

Meroni

Paolini

et al. 2022

Cellular and Molecular Gastroenterology and Hepatology

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“…Therefore, primary human skeletal muscle cells were investigated together with the WRL68 cell line, representative of mature human hepatocytes, as well as differentiated 3T3L1 cells, representative of mature murine adipocytes. The combination of human hepatocyte cell lines and murine adipocyte cell lines has already been successfully used in previous studies [18,19].…”

Section: Discussionmentioning

confidence: 99%

The nutrigenomic metabolite L‑carnitine directly modulates the activity and expression of nuclear receptors in adipocytes, liver and muscle cells

Förster¹,

Indra²,

Hofbauer³

2019

Preprint

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Background: L-carnitine is an indispensable metabolite in eukaryotic cells, which facilitates transport of long-chain fatty acids into the mitochondrial matrix for subsequent β-oxidation and helps to safeguard the acetyl-CoA level. Additionally, L-carnitine has been proven to exert a nutrigenomic effect, modulating the expression of numerous target genes. However, the diverging time-dependent effects of short-term and extended L-carnitine supplementation have not been investigated in more detail yet, especially in the interplay of adipocytes, liver and muscle cells. A cell culture model with conditions of L-carnitine deficiency and supplementation for these cell types was established to investigate the effects of L-carnitine on key nuclear receptors and their pathways.Results: L-carnitine deficiency as well as L-carnitine supplementation to hepatocytes modulated protein activity of multiple nuclear receptor pathways (RAR, RXR, VDR, PPAR, HNF4, ER, LXR). On the transcriptional level, short-term L-carnitine supplementation initially exerted an inhibitory effect on the steady state mRNA levels of PPAR-α, PPAR-δ, PPAR-γ, RAR-β , LXR-α and RXR-α in adipocytes, liver and muscle cells. However, extended L-carnitine supplementation for 24 and 48 hours led to a significant upregulation of PPAR-α and PPAR-δ , being key regulators of lipid catabolism, thereby promoting lipolysis and β-oxidation. In addition, significant differences in transcriptional modulation were found between adipocytes, liver and muscle cells. Extended L-carnitine administration to hepatocytes also modulated mRNA expression levels of nuclear receptor target genes CYP2R1 , ALDH1A1 , HSD11B2 , OGT and HMGCR.Conclusions: These findings show a clear nutrigenomic effect of L-carnitine on the protein activity and expression levels of selected nuclear receptors in different tissues, promoting lipolytic gene expression as well as decreasing transcription of adipogenic and insulin-resistance linked genes. Therefore L-carnitine supplementation obviously is a promising strategy supporting established antihyperlipidemic therapies. BackgroundLcarnitine (L3hydroxy4N-trimethylaminobutyrate) is a quaternary ammonium compound and an indispensable metabolite in all eukaryotic cells. Lcarnitine is synthesized from the essential amino

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“…Like in the intestinal lumen, another possible TNAP substrate in the liver is CD36. In HepG2 hepatocytes cultured in presence of high glucose or FA levels, TNAP expression increased in parallel with that of CD36 [ 71 , 72 ], and TNAP inhibition with levamisole or siRNA reduced triglyceride (TG) accumulation [ 71 , 73 ]. That TNAP controls CD36 activity in hepatocytes however remains to be demonstrated.…”

Section: Tnap’s Pathophysiological Functions In the Liver Bile And Intestinal Lumenmentioning

confidence: 99%

“…Since CD36 dephosphorylation facilitates FA uptake [ 44 , 45 , 46 ], if TNAP was responsible for dephosphorylating CD36, then its deficiency should lead to decreased, and not increased liver steatosis [ 14 ]. In fact, whether the function of TNAP in lipid accumulation in hepatocytes [ 71 , 72 ] relies on CD36 modulation remains obscure, because TNAP was reported to be located at the surface of lipid droplets [ 71 ], and thus not where CD36 is expected to be active. Finally, it is conceivable that TNAP indeed participates in CD36-associated FA uptake, but on other tissues than the liver, nevertheless impacting liver steatosis.…”

Section: Tnap’s Pathophysiological Functions In the Liver Bile And Intestinal Lumenmentioning

confidence: 99%

“…Alpl +/− MSCs appear to have higher levels of extracellular ATP than Alpl +/+ MSCs, suggesting that TNAP might inhibit adipocyte differentiation through ATP dephosphorylation and decreased activation of purinergic receptors [ 93 ]. On the other hand, in adipocytes, like in hepatocytes [ 71 ], TNAP was localized in association with lipid droplets, suggesting that TNAP may control adipocyte functions intracellularly [ 96 , 97 ]. In contrast with these studies, another article reported that in mature 3T3-F442A adipocytes, inhibition of TNAP activity with levamisole decreased lipolysis [ 98 ].…”

Section: Pathophysiological Tnap’s Function In Adipocytesmentioning

confidence: 99%

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TNAP: A New Multitask Enzyme in Energy Metabolism

Briolay

Bessueille

Magne

2021

IJMS

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Tissue-nonspecific alkaline phosphatase (TNAP) is mainly known for its necessary role in skeletal and dental mineralization, which relies on the hydrolysis of the mineralization inhibitor inorganic pyrophosphate (PPi). Mutations in the gene encoding TNAP leading to severe hypophosphatasia result in strongly reduced mineralization and perinatal death. Fortunately, the relatively recent development of a recombinant TNAP with a bone anchor has allowed to correct the bone defects and prolong the life of affected babies and children. Researches on TNAP must however not be slowed down, because accumulating evidence indicates that TNAP activation in individuals with metabolic syndrome (MetS) is associated with enhanced cardiovascular mortality, presumably in relation with cardiovascular calcification. On the other hand, TNAP appears to be necessary to prevent the development of steatohepatitis in mice, suggesting that TNAP plays protective roles. The aim of the present review is to highlight the known or suspected functions of TNAP in energy metabolism that may be associated with the development of MetS. The location of TNAP in liver and its function in bile excretion, lipopolysaccharide (LPS) detoxification and fatty acid transport will be presented. The expression and function of TNAP in adipocyte differentiation and thermogenesis will also be discussed. Given that TNAP is a tissue- and substrate-nonspecific phosphatase, we believe that it exerts several crucial pathophysiological functions that are just beginning to be discovered.

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The role of alkaline phosphatase in intracellular lipid accumulation in the human hepatocarcinoma cell line, HepG2

Cited by 10 publications

References 42 publications

TM6SF2/PNPLA3/MBOAT7 Loss-of-Function Genetic Variants Impact on NAFLD Development and Progression Both in Patients and in In Vitro Models

TM6SF2/PNPLA3/MBOAT7 Loss-of-Function Genetic Variants Impact on NAFLD Development and Progression Both in Patients and in In Vitro Models

The nutrigenomic metabolite L‑carnitine directly modulates the activity and expression of nuclear receptors in adipocytes, liver and muscle cells

TNAP: A New Multitask Enzyme in Energy Metabolism

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