Literature DB >> 18508126

Diacylglycerol acyltransferases: Potential roles as pharmacological targets.

Victor A Zammit1, Linda K Buckett, Andrew V Turnbull, Haja Wure, Andrew Proven.   

Abstract

Triglyceride (TG) synthesis occurs in many cell-types, but only the adipocyte is specialised for TG storage. The increased incidence of obesity and its attendant pathologies have increased interest in pharmacological strategies aimed at inhibition of triglyceride synthesis. In the liver this would also appear to offer the advantages of the prevention of steatosis and/or dyslipidaemia. The two major enzymes that have DGAT activity appear to have specialised functions, that are most evident in triglyceride-secreting tissues. The presence of triglyceride in non-adipose cells can lead to (through lipolysis), or be a marker for, undesirable complications such as insulin resistance, or can be indicative of simultaneously high capacities for triglyceride synthesis, lipolysis and oxidation of fatty acids as in highly aerobic, trained muscle. Consequently, inhibition of triglyceride synthesis may not be a straightforward strategy, either in terms of its achievement pharmacologically or in its anticipated outcomes. The metabolic complexities of triglyceride synthesis, with particular reference to the diacylglycerol acyltransferases (DGATs) are considered in this short review.

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Year:  2008        PMID: 18508126     DOI: 10.1016/j.pharmthera.2008.03.010

Source DB:  PubMed          Journal:  Pharmacol Ther        ISSN: 0163-7258            Impact factor:   12.310


  11 in total

Review 1.  Mammalian triacylglycerol metabolism: synthesis, lipolysis, and signaling.

Authors:  Rosalind A Coleman; Douglas G Mashek
Journal:  Chem Rev       Date:  2011-06-01       Impact factor: 60.622

2.  Diacylglycerol Acyltransferase 1 Is Regulated by Its N-Terminal Domain in Response to Allosteric Effectors.

Authors:  Kristian Mark P Caldo; Jeella Z Acedo; Rashmi Panigrahi; John C Vederas; Randall J Weselake; M Joanne Lemieux
Journal:  Plant Physiol       Date:  2017-08-21       Impact factor: 8.340

3.  Development of novel benzomorpholine class of diacylglycerol acyltransferase I inhibitors.

Authors:  Gang Zhou; Nicolas Zorn; Pauline Ting; Robert Aslanian; Mingxiang Lin; John Cook; Jean Lachowicz; Albert Lin; Michelle Smith; Joyce Hwa; Margaret van Heek; Scott Walker
Journal:  ACS Med Chem Lett       Date:  2014-03-01       Impact factor: 4.345

4.  Discovery of PF-04620110, a Potent, Selective, and Orally Bioavailable Inhibitor of DGAT-1.

Authors:  Robert L Dow; Jian-Cheng Li; Michael P Pence; E Michael Gibbs; Jennifer L LaPerle; John Litchfield; David W Piotrowski; Michael J Munchhof; Tara B Manion; William J Zavadoski; Gregory S Walker; R Kirk McPherson; Susan Tapley; Eliot Sugarman; Angel Guzman-Perez; Paul DaSilva-Jardine
Journal:  ACS Med Chem Lett       Date:  2011-03-18       Impact factor: 4.345

5.  Successful Strategies for Mitigation of a Preclinical Signal for Phototoxicity in a DGAT1 Inhibitor.

Authors:  Tyler J Harrison; Daniel Bauer; Alina Berdichevsky; Xin Chen; Rohit Duvadie; Benjamin Hoogheem; Panos Hatsis; Qian Liu; Justin Mao; Vasumathy Miduturu; Erik Rocheford; Frederic Zecri; Richard Zessis; Rui Zheng; Qingming Zhu; Ryan Streeper; Sejal J Patel
Journal:  ACS Med Chem Lett       Date:  2019-06-20       Impact factor: 4.345

6.  Evidence that diacylglycerol acyltransferase 1 (DGAT1) has dual membrane topology in the endoplasmic reticulum of HepG2 cells.

Authors:  Haja R Wurie; Linda Buckett; Victor A Zammit
Journal:  J Biol Chem       Date:  2011-08-16       Impact factor: 5.157

7.  The use of stable isotope-labeled glycerol and oleic acid to differentiate the hepatic functions of DGAT1 and -2.

Authors:  Jenson Qi; Wensheng Lang; John G Geisler; Ping Wang; Ioanna Petrounia; Selyna Mai; Charles Smith; Hossein Askari; Geoffrey T Struble; Robyn Williams; Sanjay Bhanot; Brett P Monia; Shariff Bayoumy; Eugene Grant; Gary W Caldwell; Matthew J Todd; Yin Liang; Micheal D Gaul; Keith T Demarest; Margery A Connelly
Journal:  J Lipid Res       Date:  2012-04-03       Impact factor: 5.922

8.  Diacylglycerol acyltransferase 2 links glucose utilization to fatty acid oxidation in the brown adipocytes.

Authors:  Zehra Irshad; Federica Dimitri; Mark Christian; Victor A Zammit
Journal:  J Lipid Res       Date:  2016-11-11       Impact factor: 5.922

Review 9.  Dietary polyunsaturated fatty acids and inflammation: the role of phospholipid biosynthesis.

Authors:  William Raphael; Lorraine M Sordillo
Journal:  Int J Mol Sci       Date:  2013-10-22       Impact factor: 5.923

10.  DGAT1 inhibitors protect pancreatic β-cells from palmitic acid-induced apoptosis.

Authors:  Jun-Shang Huang; Bin-Bin Guo; Gai-Hong Wang; Li-Min Zeng; You-Hong Hu; Ting Wang; He-Yao Wang
Journal:  Acta Pharmacol Sin       Date:  2020-07-31       Impact factor: 6.150

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