Abstract | 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: 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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Authors | Arend Bonen, Swati S Jain, Laelie A Snook, Xiao-Xia Han, Yuko Yoshida, Kathryn H Buddo, James S Lally, Elizabeth D Pask, Sabina Paglialunga, Marie-Soleil Beaudoin, Jan F C Glatz, Joost J F P Luiken, Ewa Harasim, David C Wright, Adrian Chabowski, Graham P Holloway |
Journal | Diabetologia
(Diabetologia)
Vol. 58
Issue 10
Pg. 2381-91
(Oct 2015)
ISSN: 1432-0428 [Electronic] Germany |
PMID | 26197708
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- CD36 Antigens
- Fatty Acid-Binding Proteins
- Fatty Acids
- Glucose Transporter Type 4
- Slc2a4 protein, rat
- Glucose
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Topics |
- Animals
- CD36 Antigens
(genetics, metabolism)
- Diet, High-Fat
- Fatty Acid-Binding Proteins
(metabolism)
- Fatty Acids
(metabolism)
- Glucose
(metabolism)
- Glucose Transporter Type 4
(metabolism)
- Insulin Resistance
(genetics, physiology)
- Lipid Metabolism
(genetics, physiology)
- Male
- Mitochondria
(metabolism)
- Muscle Cells
(metabolism)
- Muscle, Skeletal
(metabolism)
- Rats
- Rats, Sprague-Dawley
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