Microsomal triglyceride transfer protein and nonalcoholic fatty liver disease

Pereira, Isabel Maria Teixeira Bicudo; Stefano, José Tadeu; Oliveira, Cláudia Pinto Marques Souza de

doi:10.1586/egh.11.22

Cited by 28 publications

(20 citation statements)

References 39 publications

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“…Hepatic lipid metabolism involves three major processes: esterification, de novo synthesis and oxidation, representing lipid anabolism and catabolism, respectively . Genes such as ApoB100 , MTTP , CPT1 , PPARα , SREBP1c , PGC1α , LXRα , ChREBP , G6Pc , FAS , ACCα and SCD1 have been suggested as being responsible for the regulation of these metabolic pathways . In the present study, feeding of the high‐fat diet stimulated hepatic transcription of ApoB100 , MTTP , PPARα and SREBP1c genes in offspring from dams in the NN group, but not in offspring of dams fed the chocolate‐ and fructose‐supplemented diet, with relatively low expression of ApoB100 , MTTP , CPT1 and PPARα seen in MNHD group and decreased expression of ApoB100 and PPARα seen in the ONHD group.…”

Section: Discussionsupporting

confidence: 52%

Supplementation of the maternal diet during pregnancy with chocolate and fructose interacts with the high‐fat diet of the young to facilitate the onset of metabolic disorders in rat offspring

Zhang

Dai

Wang

et al. 2013

Clin Exp Pharma Physio

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Obesity and non-alcoholic fatty liver disease are the most common metabolic disorders in society today. Previously, we found that supplementing the maternal diet during pregnancy with chocolate and fructose has negative effects on the well-being of the offspring that were ameliorated if the offspring were fed a normal diet during postnatal life. In the present study, we investigated whether feeding offspring a high-fat diet would augment the maternal programming effects and whether extra protein supply can correct the low birth weight resulting from the chocolate-supplemented maternal diet. Pregnant Sprague-Dawley rats were divided into three groups and fed either standard chow (normal nutrition; NN), chocolate- and fructose-supplemented standard chow with casein sodium (overnutrition; ON) or the supplemented standard chow without casein sodium (malnutrition; MN) throughout pregnancy. Male offspring were weaned on either standard or high-fat chow. Dams in the MN group exhibited moderate weight gain, consumed 50% less protein (P < 0.001) but more carbohydrates during gestation and delivered pups with a 12% lower birth weight (P < 0.05) than pups in the NN group, results that are consistent with previous findings. When fed on a high-fat diet after birth, pups from dams in the MN group (MNHD) had 30% more body fat (P = 0.023) and liver triglyceride (TG) levels that were double (P < 0.01) those in offspring in the other groups, leading to fatty livers in these offspring at 14 weeks of age. Hepatic expression of the PPARα, ApoB100, MTTP, CPT1 and SREBP1c genes was significantly downregulated in the MNHD group (P < 0.05 for all), indicating changes in lipid metabolism. Although dams in the ON group exhibited marked gestational weight gain (P < 0.01), they gave birth to normal weight pups that only manifested mild increases in body fat and liver TG content (P < 0.05), without significant changes in the expression of most genes when fed with the high-fat diet. The results suggest that the extra protein supply in the form of casein sodium was able to correct some negative programming effects of the chocolate and fructose supplementation of the maternal diet, which, in conjunction with a high-fat diet in the offspring, may facilitate the onset of metabolic disorders, with impaired liver gene expression possibly a key contributor.

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Section: Discussionsupporting

confidence: 52%

Supplementation of the maternal diet during pregnancy with chocolate and fructose interacts with the high‐fat diet of the young to facilitate the onset of metabolic disorders in rat offspring

Zhang

Dai

Wang

et al. 2013

Clin Exp Pharma Physio

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show abstract

“…Interestingly, both Mtp and ApoB siRNA treatments resulted in a signifi cant decrease in many genes that are key regulators of fatty acid and triglyceride synthesis therapeutics has waned given that Mtp inhibitors can lead to increased hepatic triglycerides and liver steatosis (10)(11)(12). The fact that we observed similar fi ndings using a different modality (siRNAs) suggests that this is mediated by targeting Mtp and not a nonspecifi c effect.…”

Section: Dgat2 Silencing Attenuates Liver Steatosis Induced By Mtp Sisupporting

confidence: 53%

Rescue of Mtp siRNA-induced hepatic steatosis by DGAT2 siRNA silencing

Tep¹,

Mihaila²,

Freeman³

et al. 2012

Journal of Lipid Research

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“…Therefore, we measured protein expression of MTP and ApoB-100, which are both crucial to the assembly and secretion of triglyceride from liver (40). Contrary to the predicted hypothesis, asparaginase increased MTP protein concentrations in the livers of both WA and GA mice (two-way ANOVA significant main effect, P Ͻ 0.05; Fig.…”

Section: E287 Asparaginase Increases Fgf21mentioning

confidence: 82%

GCN2 is required to increase fibroblast growth factor 21 and maintain hepatic triglyceride homeostasis during asparaginase treatment

Wilson

Lennox

She

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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The antileukemic agent asparaginase triggers the amino acid response (AAR) in the liver by activating the eukaryotic initiation factor 2 (eIF2) kinase general control nonderepressible 2 (GCN2). To explore the mechanism by which AAR induction is necessary to mitigate hepatic lipid accumulation and prevent liver dysfunction during continued asparaginase treatment, wild-type and Gcn2 null mice were injected once daily with asparaginase or phosphate buffered saline for up to 14 days. Asparaginase induced mRNA expression of multiple AAR genes and greatly increased circulating concentrations of the metabolic hormone fibroblast growth factor 21 (FGF21) independent of food intake. Loss of Gcn2 precluded mRNA expression and circulating levels of FGF21 and blocked mRNA expression of multiple genes regulating lipid synthesis and metabolism including Fas, Ppara, Pparg, Acadm, and Scd1 in both liver and white adipose tissue. Furthermore, rates of triglyceride export and protein expression of apolipoproteinB-100 were significantly reduced in the livers of Gcn2 null mice treated with asparaginase, providing a mechanistic basis for the increase in hepatic lipid content. Loss of AAR-regulated antioxidant defenses in Gcn2 null livers was signified by reduced Gpx1 gene expression alongside increased lipid peroxidation. Substantial reductions in antithrombin III hepatic expression and activity in the blood of asparaginase-treated Gcn2 null mice indicated liver dysfunction. These results suggest that the ability of the liver to adapt to prolonged asparaginase treatment is influenced by GCN2-directed regulation of FGF21 and oxidative defenses, which, when lost, corresponds with maladaptive effects on lipid metabolism and hemostasis.

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Microsomal triglyceride transfer protein and nonalcoholic fatty liver disease

Cited by 28 publications

References 39 publications

Supplementation of the maternal diet during pregnancy with chocolate and fructose interacts with the high‐fat diet of the young to facilitate the onset of metabolic disorders in rat offspring

Supplementation of the maternal diet during pregnancy with chocolate and fructose interacts with the high‐fat diet of the young to facilitate the onset of metabolic disorders in rat offspring

Rescue of Mtp siRNA-induced hepatic steatosis by DGAT2 siRNA silencing

GCN2 is required to increase fibroblast growth factor 21 and maintain hepatic triglyceride homeostasis during asparaginase treatment

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