ArticleThe Journal of clinical investigation2007
Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistance.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers.
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Who cites it
168 citing papers in PubMed.
- Prolonged fasting-induced metabolic signatures in human skeletal muscle of lean and obese men.PloS one · 2018Trial
- Effect of acute physiological free fatty acid elevation in the context of hyperinsulinemia on fiber type-specific IMCL accumulation.Journal of applied physiology (Bethesda, Md. : 1985) · 2017Trial
- Effects of habitual aerobic exercise on the relationship between intramyocellular or extramyocellular lipid content and arterial stiffness.Journal of human hypertension · 2016Trial
- Acute free fatty acid elevation eliminates endurance training effect on insulin sensitivity.The Journal of clinical endocrinology and metabolism · 2012Trial
- Acute high-fat feeding does not prevent the improvement in glucose tolerance after resistance exercise in lean individuals.European journal of applied physiology · 2011Trial
- Training in the fasted state improves glucose tolerance during fat-rich diet.The Journal of physiology · 2010Trial
- Sex-specific alterations in mRNA level of key lipid metabolism enzymes in skeletal muscle of overweight and obese subjects following endurance exercise.Physiological genomics · 2009Trial
- Article
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- Genotype-Dependent Variations in Oxidative Stress Markers and Bioactive Proteins in Hereford Bulls: Associations withBiomolecules · 2024Article
- Roles of lipid droplets and related proteins in metabolic diseases.Lipids in health and disease · 2024Review
- Endoplasmic Reticulum Stress and Obesity.Advances in experimental medicine and biology · 2024Review
- Insulin Resistance, Obesity, and Lipotoxicity.Advances in experimental medicine and biology · 2024Review
- Role ofJournal of microbiology and biotechnology · 2023Article
- The roles of DGAT1 and DGAT2 in human myotubes are dependent on donor patho-physiological background.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Differential intracellular management of fatty acids impacts on metabolic stress-stimulated glucose uptake in cardiomyocytes.Scientific reports · 2023Article
- Lipid droplet biogenesis and functions in health and disease.Nature reviews. Endocrinology · 2023Review
- The Effects of Ketogenic Diet on Insulin Sensitivity and Weight Loss, Which Came First: The Chicken or the Egg?Nutrients · 2023Review
- Glycerolipid Synthesis and Lipid Droplet Formation in the Endoplasmic Reticulum.Cold Spring Harbor perspectives in biology · 2023Review
108 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Increased fat deposition in skeletal muscle is associated with insulin resistance. However, exercise increases both intramyocellular fat stores and insulin sensitivity, a phenomenon referred to as "the athlete's paradox". In this study, we provide evidence that augmenting triglyceride synthesis in skeletal muscle is intrinsically connected with increased insulin sensitivity. Exercise increased diacylglycerol (DAG) acyltransferase (DGAT) activity in skeletal muscle. Channeling fatty acid substrates into TG resulted in decreased DAG and ceramide levels. Transgenic overexpression of DGAT1 in mouse skeletal muscle replicated these findings and protected mice against high-fat diet-induced insulin resistance. Moreover, in isolated muscle, DGAT1 deficiency exacerbated insulin resistance caused by fatty acids, whereas DGAT1 overexpression mitigated the detrimental effect of fatty acids. The heightened insulin sensitivity in the transgenic mice was associated with attenuated fat-induced activation of DAG-responsive PKCs and the stress mediator JNK1. Consistent with these changes, serine phosphorylation of insulin receptor substrate 1 was reduced, and Akt activation and glucose 4 membrane translocation were increased. In conclusion, upregulation of DGAT1 in skeletal muscle is sufficient to recreate the athlete's paradox and illustrates a mechanism of exercise-induced enhancement of muscle insulin sensitivity. Thus, increasing muscle DGAT activity may offer a new approach to prevent and treat insulin resistance and type 2 diabetes mellitus.
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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.