ArticleDiabetes2009
Paradoxical coupling of triglyceride synthesis and fatty acid oxidation in skeletal muscle overexpressing DGAT1.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- Decoration of intramyocellular lipid droplets with PLIN5 modulates fasting-induced insulin resistance and lipotoxicity in humans.Diabetologia · 2016Trial
- miR-10c TargetsInternational journal of molecular sciences · 2025Article
- Plin5: A potential therapeutic target for type 2 diabetes mellitus.Diabetology & metabolic syndrome · 2025Article
- Tissue-Specific Mechanism of Fat Distribution in Teleosts: Comparative Analysis Between Two Carnivorous Marine Species, Golden Pompano (Aquaculture nutrition · 2025Article
- Butyrate enhances CPT1A activity to promote fatty acid oxidation and iTreg differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Dietary Olive Oil Intake Improves Running Endurance with Intramuscular Triacylglycerol Accumulation in Mice.Nutrients · 2021Article
- Association of DGAT1 With Cattle, Buffalo, Goat, and Sheep Milk and Meat Production Traits.Frontiers in veterinary science · 2021Review
- CGI-58: Versatile Regulator of Intracellular Lipid Droplet Homeostasis.Advances in experimental medicine and biology · 2020Review
- Endothelial cell CD36 optimizes tissue fatty acid uptake.The Journal of clinical investigation · 2018Article
- BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice.The journals of gerontology. Series A, Biological sciences and medical sciences · 2017Article
- The Contribution of Singlet Oxygen to Insulin Resistance.Oxidative medicine and cellular longevity · 2017Review
- Analysis of Differentially Expressed Genes in Gastrocnemius Muscle between DGAT1 Transgenic Mice and Wild-Type Mice.BioMed research international · 2017Article
- Lipid Use and Misuse by the Heart.Circulation research · 2016Review
- Muscle-specific deletion of comparative gene identification-58 (CGI-58) causes muscle steatosis but improves insulin sensitivity in male mice.Endocrinology · 2015Article
- Memory CD8(+) T cells use cell-intrinsic lipolysis to support the metabolic programming necessary for development.Immunity · 2014Article
- Creb coactivators direct anabolic responses and enhance performance of skeletal muscle.The EMBO journal · 2014Article
- Reduced incorporation of fatty acids into triacylglycerol in myotubes from obese individuals with type 2 diabetes.Diabetes · 2014Article
- Article
- Lipoprotein lipase activity is required for cardiac lipid droplet production.Journal of lipid research · 2014Article
- Perilipins: lipid droplet coat proteins adapted for tissue-specific energy storage and utilization, and lipid cytoprotection.Biochimie · 2014Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
objectiveTransgenic expression of diacylglycerol acyltransferase-1 (DGAT1) in skeletal muscle leads to protection against fat-induced insulin resistance despite accumulation of intramuscular triglyceride, a phenomenon similar to what is known as the "athlete paradox." The primary objective of this study is to determine how DGAT1 affects muscle fatty acid oxidation in relation to whole-body energy metabolism and insulin sensitivity. RESEARCH DESIGN AND
methodsWe first quantified insulin sensitivity and the relative tissue contributions to the improved whole-body insulin sensitivity in muscle creatine kisase (MCK)-DGAT1 transgenic mice by hyperinsulinemic-euglycemic clamps. Metabolic consequences of DGAT1 overexpression in skeletal muscles were determined by quantifying triglyceride synthesis/storage (anabolic) and fatty acid oxidation (catabolic), in conjunction with gene expression levels of representative marker genes in fatty acid metabolism. Whole-body energy metabolism including food consumption, body weights, oxygen consumption, locomotor activity, and respiration exchange ratios were determined at steady states.
resultsMCK-DGAT1 mice were protected against muscle lipoptoxicity, although they remain susceptible to hepatic lipotoxicity. While augmenting triglyceride synthesis, DGAT1 overexpression also led to increased muscle mitochondrial fatty acid oxidation efficiency, as compared with wild-type muscles. On a high-fat diet, MCK-DGAT1 mice displayed higher basal metabolic rates and 5-10% lower body weights compared with wild-type littermates, whereas food consumption was not different.
conclusionsDGAT1 overexpression in skeletal muscle led to parallel increases in triglyceride synthesis and fatty acid oxidation. Seemingly paradoxical, this phenomenon is characteristic of insulin-sensitive myofibers and suggests that DGAT1 plays an active role in metabolic "remodeling" of skeletal muscle coupled with insulin sensitization.
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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.