The Role of Diacylglycerol Acyltransferase (DGAT) 1 and 2 in Cardiac Metabolism and Function

It is increasingly recognized that synthesis and turnover of cardiac triglyceride (TG) play a pivotal role in the regulation of lipid metabolism and function of the heart. The last step in TG synthesis is catalyzed by diacylglycerol:acyltransferase (DGAT) which esterifies the diacylglycerol with a f...

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Bibliographic Details
Published in:Scientific reports 2018-03, Vol.8 (1), p.4983-10, Article 4983
Main Authors: Roe, Nathan D., Handzlik, Michal K., Li, Tao, Tian, Rong
Format: Article
Language:English
Subjects:
631/443/319/2723
631/443/592/75/2099
Acyltransferase
Diacylglycerol O-acyltransferase
Diglycerides
Fatty acids
Heart
Heart diseases
High fat diet
Humanities and Social Sciences
Inactivation
Isoforms
Lipid metabolism
Metabolism
multidisciplinary
Muscle contraction
Oxidation
Rodents
Science
Science (multidisciplinary)
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Summary:It is increasingly recognized that synthesis and turnover of cardiac triglyceride (TG) play a pivotal role in the regulation of lipid metabolism and function of the heart. The last step in TG synthesis is catalyzed by diacylglycerol:acyltransferase (DGAT) which esterifies the diacylglycerol with a fatty acid. Mammalian heart has two DGAT isoforms, DGAT1 and DGAT2, yet their roles in cardiac metabolism and function remain poorly defined. Here, we show that inactivation of DGAT1 or DGAT2 in adult mouse heart results in a moderate suppression of TG synthesis and turnover. Partial inhibition of DGAT activity increases cardiac fatty acid oxidation without affecting PPARĪ± signaling, myocardial energetics or contractile function. Moreover, coinhibition of DGAT1/2 in the heart abrogates TG turnover and protects the heart against high fat diet-induced lipid accumulation with no adverse effects on basal or dobutamine-stimulated cardiac function. Thus, the two DGAT isoforms in the heart have partially redundant function, and pharmacological inhibition of one DGAT isoform is well tolerated in adult hearts.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-23223-7