Extremely rapid increase in fatty acid transport and intramyocellular lipid accumulation but markedly delayed insulin resistance after high fat feeding in rats.

Autor: Bonen A; Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, Canada, N1G 2W1. arend.bonen@gmail.com., Jain SS; Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, Canada, N1G 2W1., Snook LA; Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, Canada, N1G 2W1., Han XX; Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, Canada, N1G 2W1., Yoshida Y; Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, Canada, N1G 2W1., Buddo KH; Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, Canada, N1G 2W1., Lally JS; Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, Canada, N1G 2W1., Pask ED; Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, Canada, N1G 2W1., Paglialunga S; Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, Canada, N1G 2W1., Beaudoin MS; Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, Canada, N1G 2W1., Glatz JF; Department of Molecular Genetics, Maastricht University, Maastricht, the Netherlands., Luiken JJ; Department of Molecular Genetics, Maastricht University, Maastricht, the Netherlands., Harasim E; Department of Physiology, Medical University of Bialystok, Bialystok, Poland., Wright DC; Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, Canada, N1G 2W1., Chabowski A; Department of Physiology, Medical University of Bialystok, Bialystok, Poland., Holloway GP; Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, Canada, N1G 2W1.
Jazyk: angličtina
Zdroj: Diabetologia [Diabetologia] 2015 Oct; Vol. 58 (10), pp. 2381-91. Date of Electronic Publication: 2015 Jul 22.
DOI: 10.1007/s00125-015-3691-8
Abstrakt: Aims/hypothesis: The 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.
Methods: We 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.
Results: Within 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.
Databáze: MEDLINE
Externí odkaz: