From whole body to cellular models of hepatic triglyceride metabolism: man has got to know his limitations

Green, Charlotte; Pramfalk, Camilla; Morten, Karl; Hodson, Leanne

doi:10.1152/ajpendo.00192.2014

Cited by 32 publications

(37 citation statements)

References 247 publications

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“…The ideal, "golden standard" model for studying triglyceride metabolism in the human liver is by using primary human hepatocytes. Freshly isolated human hepatocytes secrete nascent TRLs within the VLDL size-range, similar to the secreted lipoproteins found in human serum 91 . However, fresh human liver samples are rarely available and the subsequent isolation of hepatocytes is dependent on delicate isolation procedures.…”

Section: Selection Of a Model System For The Study Of Hepatic Triglycmentioning

confidence: 63%

PNPLA2 influences secretion of triglyceride-rich lipoproteins by human hepatoma cells

Taxiarchis

Mahdessian

Silveira

et al. 2019

Journal of Lipid Research

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Section: Selection Of a Model System For The Study Of Hepatic Triglycmentioning

confidence: 63%

PNPLA2 influences secretion of triglyceride-rich lipoproteins by human hepatoma cells

Taxiarchis

Mahdessian

Silveira

et al. 2019

Journal of Lipid Research

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“…One approach to reducing TAG levels in NAFLD is to induce PPARα target genes in hepatic fatty acid β-oxidation (63, 176, 225, 226) and lipoprotein metabolism (72, 227–229). In NAFLD individuals, not segregated by T94A or other genotype, fibrate PPARα activators do not uniformly lower TAG and CVD risk (230, 231).…”

Section: Fabp1 In Human Health: Impact Of the Human Fabp1 T94a Variantmentioning

confidence: 99%

Fatty Acid Binding Protein‐1 (FABP1) and the Human FABP1 T94A Variant: Roles in the Endocannabinoid System and Dyslipidemias

Schroeder

McIntosh

Martin

et al. 2016

Lipids

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The first discovered member of the mammalian FABP family, liver fatty acid binding protein (FABP1, L-FABP), occurs at high cytosolic concentration in liver, intestine and in the case of humans also in kidney. While the rat FABP1 is well studied, the extent these findings translate to human FABP1 is not clear—especially in view of recent studies showing that endocannabinoids and cannabinoids represent novel rat FABP1 ligands and FABP1 gene ablation impacts the hepatic endocannabinoid system, known to be involved in non-alcoholic fatty liver (NAFLD) development. Although not detectable in brain, FABP1 ablation nevertheless also impacts brain endocannabinoids. Despite overall tertiary structure similarity, human FABP1 differs significantly from rat FABP1 in secondary structure, much larger ligand binding cavity, and affinities/specificities for some ligands. Moreover, while both mouse and human FABP1 mediate ligand induction of peroxisome proliferator activated receptor-α, (PPARα), they differ markedly in pattern of genes induced. This is critically important because a highly prevalent human SNP (26–38% minor allele frequency and 8.3±1.9% homozygous) results in a FABP1 T94A substitution that further accentuates these species differences. The human FABP1 T94A variant is associated with altered body mass index (BMI), clinical dyslipidemias (elevated plasma triglycerides and LDL cholesterol), atherothrombotic cerebral infarction, and non-alcoholic fatty liver disease (NAFLD). Resolving human FABP1 and the T94A variant’s impact on the endocannabinoid and cannabinoid system is an exciting challenge due to the importance of this system on hepatic lipid accumulation as well as behavior, pain, inflammation, and satiety.

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“…; Green et al. 2015b). As a result, the aim of this work was to comprehensively characterize FA metabolism in both HepG2 and Huh7 cells and investigate whether human serum could improve their functionality.…”

Section: Introductionmentioning

confidence: 99%

“…NAFLD covers a spectrum of conditions, the first of which is steatosis, where lipid droplets (LDs) primarily containing triacylglycerol (TAG), form within hepatocytes. Increased intrahepatocellular storage of TAG can result from elevated delivery or synthesis of fatty acids (FAs), reduced secretion or oxidation of FAs, or both: several of these processes have been shown to be perturbed in individuals with NAFLD (Diraison et al 2003;Fabbrini et al 2008;Lambert et al 2014;Green et al 2015b).…”

Section: Introductionmentioning

confidence: 99%

“…Although there are many reported similarities in the function of HepG2 and Huh7 cells, studies directly comparing the two cell lines are surprisingly sparse (Meex et al 2011;Green et al 2015b). As a result, the aim of this work was to comprehensively characterize FA metabolism in both HepG2 and Huh7 cells and investigate whether human serum could improve their functionality.…”

Section: Introductionmentioning

confidence: 99%

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In vitro cellular models of human hepatic fatty acid metabolism: differences between Huh7 and HepG2 cell lines in human and fetal bovine culturing serum

et al. 2017

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Human primary hepatocytes are the gold standard for investigating lipid metabolism in nonalcoholic fatty liver disease (NAFLD); however, due to limitations including availability and donor variability, the hepatoma cell lines Huh7 and HepG2 are commonly used. Culturing these cell lines in human serum (HS) has been reported to improve functionality; however, direct comparison of fatty acid (FA) metabolism in response to culturing in HS is lacking. The aim of this study was to compare FA metabolism between HepG2 and Huh7 cells in response to culturing in different sera. Both HepG2 and Huh7 cells were grown in media containing 11 mmol/L glucose and either 2% HS or 10% fetal bovine serum. After 3 days, insulin and insulin‐like growth factor‐1 signaling were measured. At 7 days, intracellular triacylglycerol (TAG) and media 3‐hydroxybutyrate, TAG and apolipoprotein B were measured, as was the FA composition of intracellular TAG and phospholipids. Both cell lines demonstrated higher levels of polyunsaturated fatty acid content, increased insulin sensitivity, higher media TAG levels and increased FA oxidation when cultured in HS. Notably, independent of serum type, Huh7 cells had higher intracellular TAG compared to HepG2 cells, which was in part attributable to a higher de novo lipogenesis. Our data demonstrate that intrahepatocellular FA metabolism is different between cell lines and influenced by culturing sera. As a result, when developing a physiologically‐relevant model of FA metabolism that could be developed for the study of NAFLD, consideration of both parameters is required.

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From whole body to cellular models of hepatic triglyceride metabolism: man has got to know his limitations

Cited by 32 publications

References 247 publications

PNPLA2 influences secretion of triglyceride-rich lipoproteins by human hepatoma cells

PNPLA2 influences secretion of triglyceride-rich lipoproteins by human hepatoma cells

Fatty Acid Binding Protein‐1 (FABP1) and the Human FABP1 T94A Variant: Roles in the Endocannabinoid System and Dyslipidemias

In vitro cellular models of human hepatic fatty acid metabolism: differences between Huh7 and HepG2 cell lines in human and fetal bovine culturing serum

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