ArticleJournal of lipid research2013
Comparison of the pharmacological profiles of murine antisense oligonucleotides targeting apolipoprotein B and microsomal triglyceride transfer protein.
Article in Journal of lipid research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Complex effects of inhibiting hepatic apolipoprotein B100 synthesis in humans.Science translational medicine · 2016Trial
- Tripterygium glycosides improve abnormal lipid deposition in nephrotic syndrome rat models.Renal failure · 2023Article
- Nuclear envelope-localized torsinA-LAP1 complex regulates hepatic VLDL secretion and steatosis.The Journal of clinical investigation · 2019Article
- The Forgotten Lipids: Triglycerides, Remnant Cholesterol, and Atherosclerotic Cardiovascular Disease Risk.Endocrine reviews · 2019Review
- Heparin-binding EGF-like growth factor (HB-EGF) antisense oligonucleotide protected against hyperlipidemia-associated atherosclerosis.Nutrition, metabolism, and cardiovascular diseases : NMCD · 2019Article
- Antisense oligonucleotide and thyroid hormone conjugates for obesity treatment.Scientific reports · 2017Article
- From the Cover: The Minipig is a Suitable Non-Rodent Model in the Safety Assessment of Single Stranded Oligonucleotides.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Prevention of hepatic fibrosis with liver microsomal triglyceride transfer protein deletion in liver fatty acid binding protein null mice.Hepatology (Baltimore, Md.) · 2017Article
- Article
- Inhibition of apolipoprotein B synthesis stimulates endoplasmic reticulum autophagy that prevents steatosis.The Journal of clinical investigation · 2016Article
- Insulin resistance induces posttranslational hepatic sortilin 1 degradation in mice.The Journal of biological chemistry · 2015Article
- Differential impact of hepatic deficiency and total body inhibition of MTP on cholesterol metabolism and RCT in mice.Journal of lipid research · 2014Article
- Hepatic Mttp deletion reverses gallstone susceptibility in L-Fabp knockout mice.Journal of lipid research · 2014Article
- The endoplasmic reticulum coat protein II transport machinery coordinates cellular lipid secretion and cholesterol biosynthesis.The Journal of biological chemistry · 2014Article
- Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice.PloS one · 2014Article
- Antisense technology: an emerging platform for cardiovascular disease therapeutics.Journal of cardiovascular translational research · 2013Review
- Lipotoxicity in the liver.World journal of hepatology · 2013Review
- Supplementary site interactions are critical for the regulation of microsomal triglyceride transfer protein by microRNA-30c.Nutrition & metabolism · 2013Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapeutic agents that suppress apolipoprotein B (apoB) and microsomal triglyceride transfer protein (MTP) levels/activity are being developed in the clinic to benefit patients who are unable to reach target LDL-C levels with maximally tolerated lipid-lowering drugs. To compare and contrast the metabolic consequences of reducing these targets, murine-specific apoB or MTP antisense oligonucleotides (ASOs) were administered to chow-fed and high fat-fed C57BL/6 or to chow-fed and Western diet-fed LDLr⁻/⁻ mice for periods ranging from 2 to 12 weeks, and detailed analyses of various factors affecting fatty acid metabolism were performed. Administration of these drugs significantly reduced target hepatic mRNA and protein, leading to similar reductions in hepatic VLDL/triglyceride secretion. MTP ASO treatment consistently led to increases in hepatic triglyceride accumulation and biomarkers of hepatotoxicity relative to apoB ASO due in part to enhanced expression of peroxisome proliferator activated receptor γ target genes and the inability to reduce hepatic fatty acid synthesis. Thus, although both drugs effectively lowered LDL-C levels in mice, the apoB ASO produced a more positive liver safety profile.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.