Furthermore, the low-frequency E167K variant of TM6SF2 and rare mutations in APOB, which impair very low-density lipoproteins secretion, predispose to progressive fatty liver.
Partial MTP inhibition using small molecule inhibitors, such as lomitapide, can effectively lower plasma low-density lipoprotein-cholesterol and apolipoprotein B levels, but is associated with gastrointestinal side effects and hepatic steatosis, whose long-term sequelae remain unclear; lomitapide has accordingly only been approved as a treatment for homozygous familial hypercholesterolemia.
We used exome sequencing to discover a novel nonsense mutation in exon 26 of APOB (p.K2240X) responsible for low cholesterol and fatty liver in a large kindred.
These findings identify miR-30c as a novel therapeutic target that coordinately reduces lipid biosynthesis and lipoprotein secretion to suppress circulating apoB lipoproteins, while sparing the liver from steatosis.
Hepatitis C virus (HCV) infection is associated to dysregulation of apoB-100 secretion and steatosis; however, the molecular mechanism by which HCV affects the apoB-100 secretion is not understood.
The aim of this study was to examine the frequency of two polymorphisms in Brazilian patients with biopsy-proven simple steatosis or non-alcoholic steatohepatitis (NASH): -493 G/T in the MTP gene, which codes the protein responsible for transferring triglycerides to nascent apolipoprotein B, and -129 C/T in the GCLC gene, which codes the catalytic subunit of glutamate-cystein ligase in the formation of glutathione.
Moreover, very low-density lipoprotein (VLDL) subclass analysis showed that the VLDL2 fraction of the fatty liver subgroup contained significantly less cholesterol and triglycerides (P = .02 for both parameters), which was likely explained by a decreased VLDL2 particle number because VLDL2 apolipoprotein B levels tended to be lower (P = .08).
This steatosis was associated with aberrant microsomal apolipoprotein (apo) B-100 and microsomal triglyceride transfer protein (MTP) content, hypotriglyceridemia, hypocholesterolemia and abnormalities in both circulating lipoprotein composition and size.
Familial hypobetalipoproteinaemia (FHBL) is a codominant disorder characterised by fatty liver and reduced plasma levels of low-density lipoprotein (LDL) and its protein constituent apolipoprotein B (apoB).
We conclude that hepatic steatosis in apoB/BATless mice is associated with elevated rates of hepatic lipogenesis that are linked directly to increased hepatic expression of PPARgamma2.
Fatty liver is frequent in the apolipoprotein B (apoB)-defective genetic form of familial hypobetalipoproteinemia (FHBL), but interindividual variability in liver fat is large.
The cells with steatosis showed increased levels of intracellular triglycerides and apolipoprotein B, which were reduced in the presence of bezafibrate at 100 mug/ml.
Familial hypobetalipoproteinemia (FHBL) is a genetically heterogeneous condition characterized by very low apolipoprotein B (apoB) concentrations in plasma and/or low levels of LDL-cholesterol (LDL-C) with a propensity to developing fatty liver.
This study suggests that: i) fatty liver invariably develops in FHBL carriers of short and medium-size truncated apoBs (< apoB-48), but its occurrence needs additional environmental factors in carriers of longer apoB forms; ii) intestinal lipid malabsorption develops only in carriers of short truncated apoBs, which are not secreted into the plasma; and iii) cerebrovascular disease due to premature atherosclerosis may occur even in FHBL subjects.
We suggest that (1) steatosis is associated with increased ApoA-I mRNA; (2) fibrosis is associated with decreased serum ApoA-I, probably caused by a posttranscriptional mechanism; (3) severe alcohol-induced cirrhosis is associated with a nonspecific decrease in ApoA-I and ApoB mRNA; and (4) in contrast to ApoA-I mRNA, the ApoB mRNA level makes a slight contribution to the ApoB serum concentration.