ArticleThe Journal of biological chemistry2014
Cardiomyocyte-specific loss of diacylglycerol acyltransferase 1 (DGAT1) reproduces the abnormalities in lipids found in severe heart failure.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 72 citations in OpenAlex.
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- Lipid droplet-associated proteins: Roles in cardiovascular diseases.Journal of lipid research · 2026Review
- Lipid droplets beyond storage: Cellular metabolic modulator in the diabetic heart (Review).International journal of molecular medicine · 2026Review
- Lipotoxicity in Diabetic Cardiomyopathy: Molecular Basis and Emerging Therapeutic Targets.International journal of molecular sciences · 2026Review
- Sphingolipids in human disease: organ-specific pathologies, chain-length-dependent effects, and translational implications.Journal of translational medicine · 2026Review
- Essential Biology of Lipid Droplets.Annual review of biochemistry · 2025Review
- Omics Approaches to Study Perilipins and Their Significant Biological Role in Cardiometabolic Disorders.International journal of molecular sciences · 2025Review
- Sphingolipid Metabolism and Signalling Pathways in Heart Failure: From Molecular Mechanism to Therapeutic Potential.Journal of inflammation research · 2025Review
- Glycosphingolipids in Cardiovascular Disease: Insights from Molecular Mechanisms and Heart Failure Models.Biomolecules · 2024Review
- Lipid droplets and fatty acid-induced lipotoxicity: in a nutshell.FEBS letters · 2024Article
- Article
- Cardiac lipid metabolism, mitochondrial function, and heart failure.Cardiovascular research · 2023Review
- Glycerolipid Synthesis and Lipid Droplet Formation in the Endoplasmic Reticulum.Cold Spring Harbor perspectives in biology · 2023Review
- Integrated Control of Fatty Acid Metabolism in Heart Failure.Metabolites · 2023Review
- Circulating sphingolipids in heart failure.Frontiers in cardiovascular medicine · 2023Review
- DGAT1 activity synchronises with mitophagy to protect cells from metabolic rewiring by iron depletion.The EMBO journal · 2022Article
- Cardiac Hypertrophy: From Pathophysiological Mechanisms to Heart Failure Development.Reviews in cardiovascular medicine · 2022Review
- The regulation, function, and role of lipophagy, a form of selective autophagy, in metabolic disorders.Cell death & disease · 2022Review
- Notoginsenoside R1 Ameliorates Cardiac Lipotoxicity Through AMPK Signaling Pathway.Frontiers in pharmacology · 2022Article
- Plin5, a New Target in Diabetic Cardiomyopathy.Oxidative medicine and cellular longevity · 2022Review
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Diacylglycerol acyltransferase 1 (DGAT1) catalyzes the final step in triglyceride synthesis, the conversion of diacylglycerol (DAG) to triglyceride. Dgat1(-/-) mice exhibit a number of beneficial metabolic effects including reduced obesity and improved insulin sensitivity and no known cardiac dysfunction. In contrast, failing human hearts have severely reduced DGAT1 expression associated with accumulation of DAGs and ceramides. To test whether DGAT1 loss alone affects heart function, we created cardiomyocyte-specific DGAT1 knock-out (hDgat1(-/-)) mice. hDgat1(-/-) mouse hearts had 95% increased DAG and 85% increased ceramides compared with floxed controls. 50% of these mice died by 9 months of age. The heart failure marker brain natriuretic peptide increased 5-fold in hDgat1(-/-) hearts, and fractional shortening (FS) was reduced. This was associated with increased expression of peroxisome proliferator-activated receptor α and cluster of differentiation 36. We crossed hDgat1(-/-) mice with previously described enterocyte-specific Dgat1 knock-out mice (hiDgat1(-/-)). This corrected the early mortality, improved FS, and reduced cardiac ceramide and DAG content. Treatment of hDgat1(-/-) mice with the glucagon-like peptide 1 receptor agonist exenatide also improved FS and reduced heart DAG and ceramide content. Increased fatty acid uptake into hDgat1(-/-) hearts was normalized by exenatide. Reduced activation of protein kinase Cα (PKCα), which is increased by DAG and ceramides, paralleled the reductions in these lipids. Our mouse studies show that loss of DGAT1 reproduces the lipid abnormalities seen in severe human heart failure.
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