A pharmacologic increase in activity of plasma transaminase derived from small intestine in animals receiving an acyl CoA: diacylglycerol transferase (DGAT) 1 inhibitor

The Journal of Toxicological Sciences
Hideaki YokoyamaShoichiro Sugai

Abstract

Acyl CoA: diacylglycerol acyltransferase (DGAT) 1 is an enzyme that catalyzes the re-synthesis of triglycerides (TG) from free fatty acids and diacylglycerol. JTT-553 is a DGAT1 inhibitor and exhibits its pharmacological action (inhibition of re-synthesis of TG) in the enterocytes of the small intestine leading to suppression of a postprandial elevation of plasma lipids. After repeated oral dosing JTT-553 in rats and monkeys, plasma transaminase levels were increased but there were neither changes in other hepatic function parameters nor histopathological findings suggestive of hepatotoxicity. Based on the results of exploratory studies for investigation of the mechanism of the increase in transaminase levels, plasma transaminase levels were increased after dosing JTT-553 only when animals were fed after dosing and a main factor in the diet contributing to the increase in plasma transaminase levels was lipids. After dosing JTT-553, transaminase levels were increased in the small intestine but not in the liver, indicating that the origin of transaminase increased in the plasma was not the liver but the small intestine where JTT-553 exhibits its pharmacological action. The increase in small intestinal transaminase levels was due ...Continue Reading

References

Oct 1, 1978·Journal of Comparative Pathology·R B Clampitt, R J Hart
Jan 1, 1980·Annual Review of Biochemistry·R M Bell, R A Coleman
Oct 1, 1980·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·A PalouM Alemany
Jan 1, 1996·Progress in Lipid Research·R Lehner, A Kuksis
Aug 4, 1998·The Journal of Nutrition·G Wu
Oct 3, 1998·The Journal of Biological Chemistry·P OelkersS L Sturley
Jun 20, 2000·The American Journal of Cardiology·K G Tolman
Aug 2, 2001·The Journal of Biological Chemistry·S CasesR V Farese
Jan 31, 2002·Annual Review of Medicine·Roger H Unger
Jan 18, 2003·American Journal of Physiology. Endocrinology and Metabolism·Tony K T LamAdria Giacca
Aug 2, 2003·The New England Journal of Medicine·William M Lee
Jan 1, 1957·Annual Review of Biochemistry·E P KENNEDY
Dec 5, 2003·Progress in Lipid Research·Rosalind A Coleman, Douglas P Lee
Jul 16, 2005·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Sarah Gould, Robert C Scott
Jul 31, 2007·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Shashi K Ramaiah
Aug 5, 2009·The Journal of Toxicological Sciences·Akio KobayashiKayoko Shimoi
Nov 6, 2009·American Journal of Physiology. Endocrinology and Metabolism·Matthew D BrussMarc K Hellerstein
Oct 12, 2010·The Journal of Toxicological Sciences·Akio KobayashiKayoko Shimoi
Jun 2, 2011·The Journal of Toxicological Sciences·Akio KobayashiKayoko Shimoi

❮ Previous
Next ❯

Citations

Sep 4, 2020·The Journal of Toxicological Sciences·Akio KobayashiShoichiro Sugai

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.