ArticleDiabetologia2015
Extremely rapid increase in fatty acid transport and intramyocellular lipid accumulation but markedly delayed insulin resistance after high fat feeding in rats.
Article in Diabetologia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- The Effect of High-Fat Diet on Intramyocellular Lipid Content in Healthy Adults: A Systematic Review, Meta-Analysis, and Meta-Regression.The Journal of nutrition · 2024Pooled it
- Lipid metabolism in age-related musculoskeletal disorders: insights into sarcopenia and osteoporosis.BMC biology · 2025Review
- Article
- FoxO1-zDHHC4-CD36 S-Acylation Axis Drives Metabolic Dysfunction in Diabetes.Circulation research · 2025Article
- Oxidative stress and pediatric diabetic cardiovascular complications: emerging research and clinical applications.American journal of physiology. Heart and circulatory physiology · 2025Review
- NLRP3 inflammasomes pathway: a key target for Metformin.Inflammopharmacology · 2025Review
- Article
- Intramuscular diacylglycerol accumulates with acute hyperinsulinemia in insulin-resistant phenotypes.American journal of physiology. Endocrinology and metabolism · 2024Article
- Ceramides as Emerging Players in Cardiovascular Disease: Focus on Their Pathogenetic Effects and Regulation by Diet.Advances in nutrition (Bethesda, Md.) · 2024Review
- Potential regulatory role of PGC-1α within the skeletal muscle during metabolic adaptations in response to high-fat diet feeding in animal models.Pflugers Archiv : European journal of physiology · 2024Review
- The impact of bed rest on human skeletal muscle metabolism.Cell reports. Medicine · 2024Article
- The role of acetylation in obesity-induced cardiac metabolic alterations.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2024Review
- mTORC1 and SGLT2 Inhibitors-A Therapeutic Perspective for Diabetic Cardiomyopathy.International journal of molecular sciences · 2023Review
- Article
- Insights into the development of insulin resistance: Unraveling the interaction of physical inactivity, lipid metabolism and mitochondrial biology.Frontiers in physiology · 2023Review
- Unveiling the Vital Role of Long Non-Coding RNAs in Cardiac Oxidative Stress, Cell Death, and Fibrosis in Diabetic Cardiomyopathy.Antioxidants (Basel, Switzerland) · 2022Review
- Ketone Body Exposure of Cardiomyocytes Impairs Insulin Sensitivity and Contractile Function through Vacuolar-Type HInternational journal of molecular sciences · 2022Article
- Review
- Reduced Fatty Acid Use from CD36 Deficiency Deteriorates Streptozotocin-Induced Diabetic Cardiomyopathy in Mice.Metabolites · 2021Article
- Effects of Lipid Overload on Heart in Metabolic Diseases.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2021Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
Abstract
aims/hypothesisThe mechanisms for diet-induced intramyocellular lipid accumulation and its association with insulin resistance remain contentious. In a detailed time-course study in rats, we examined whether a high-fat diet increased intramyocellular lipid accumulation via alterations in fatty acid translocase (FAT/CD36)-mediated fatty acid transport, selected enzymes and/or fatty acid oxidation, and whether intramyocellular lipid accretion coincided with the onset of insulin resistance.
methodsWe measured, daily (on days 1-7) and/or weekly (for 6 weeks), the diet-induced changes in circulating substrates, insulin, sarcolemmal substrate transporters and transport, selected enzymes, intramyocellular lipids, mitochondrial fatty acid oxidation and basal and insulin-stimulated sarcolemmal GLUT4 and glucose transport. We also examined whether upregulating fatty acid oxidation improved glucose transport in insulin-resistant muscles. Finally, in Cd36-knockout mice, we examined the role of FAT/CD36 in intramyocellular lipid accumulation, insulin sensitivity and diet-induced glucose intolerance.
resultsWithin 2-3 days, diet-induced increases occurred in insulin, sarcolemmal FAT/CD36 (but not fatty acid binding protein [FABPpm] or fatty acid transporter [FATP]1 or 4), fatty acid transport and intramyocellular triacylglycerol, diacylglycerol and ceramide, independent of enzymatic changes or muscle fatty acid oxidation. Diet-induced increases in mitochondria and mitochondrial fatty acid oxidation and impairments in insulin-stimulated glucose transport and GLUT4 translocation occurred much later (≥21 days). FAT/CD36 ablation impaired insulin-stimulated fatty acid transport and lipid accumulation, improved insulin sensitivity and prevented diet-induced glucose intolerance. Increasing fatty acid oxidation in insulin-resistant muscles improved glucose transport. CONCLUSIONS/INTERPRETATIONS: High-fat feeding rapidly increases intramyocellular lipids (in 2-3 days) via insulin-mediated upregulation of sarcolemmal FAT/CD36 and fatty acid transport. The 16-19 day delay in the onset of insulin resistance suggests that additional mechanisms besides intramyocellular lipids contribute to this pathology.
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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.