Abstract
Increased caloric intake and physical inactivity can lead to the development of insulin resistance and puts a large burden on the Western society. Often increased caloric intake is associated with elevated plasma fatty acid concentrations and decreased insulin sensitivity and it is now recognized
that the current worldwide obesity epidemic has resulted in the increased prevalence of “metabolic disease clusters”, including type 2 diabetes, fatty liver disease and dyslipidemia. Excessive plasma lipids can result in the accumulation of lipid metabolites at ectopic sites including skeletal muscle and liver. This peripheral intramyocellular and intrahepatic lipid accumulation is associated with
tissue-specific and whole body insulin resistance and, in the case of the liver non-alcoholic fatty liver disease. Studies show that regular exercise can reduce hepatic lipid content and enhance liver health. In high-fat diet induced obesity in mice, we observed an increased muscle and liver lipid content, analyzed by mass spectrometry, concomitant with decreased glucose tolerance. We observed that treadmill exercise-training in high-fat fed mice resulted in a reduction in the lipid
content in the liver, but not in muscle, and in improved glucose tolerance. These data provide evidence that exercise-training may be a viable therapeutic intervention to prevent, or at least slow the progression of fatty liver that is associated with nutrient overload.
In skeletal muscle, multiple regulatory sites for fatty acid utilization exist; amongst these is fatty acid transport across the plasma membrane. Data suggest that the transmembrane transport of fatty acid into cells involves a protein mediated transport, involving the fatty acid transporter FAT/CD36. Herein we show that FAT/CD36 is important for fatty acid uptake and oxidation during isolated muscle contractions. On the contrary, previous observations suggest that a permanent relocation of FAT/CD36 protein to the sarcolemma induces intracellular lipid accumulation, resulting in insulin resistance. Therefore, FAT/CD36 has been linked to insulin resistance. Whether increased FAT/CD36 protein at the sarcolemma is an early event in the development of decreased insulin sensitivity or whether it is a consequence of chronic oversupply of calories, increased plasma fatty acids or chronically altered metabolism is not known. We show here that a high-fat diet-induced decrease in insulin sensitivity in healthy humans is independent of a relocation or up-regulation of FAT/CD36 protein at the sarcolemma and that the accumulation of intramyocellular lipid content after a high-fat diet is independent of such an event.
that the current worldwide obesity epidemic has resulted in the increased prevalence of “metabolic disease clusters”, including type 2 diabetes, fatty liver disease and dyslipidemia. Excessive plasma lipids can result in the accumulation of lipid metabolites at ectopic sites including skeletal muscle and liver. This peripheral intramyocellular and intrahepatic lipid accumulation is associated with
tissue-specific and whole body insulin resistance and, in the case of the liver non-alcoholic fatty liver disease. Studies show that regular exercise can reduce hepatic lipid content and enhance liver health. In high-fat diet induced obesity in mice, we observed an increased muscle and liver lipid content, analyzed by mass spectrometry, concomitant with decreased glucose tolerance. We observed that treadmill exercise-training in high-fat fed mice resulted in a reduction in the lipid
content in the liver, but not in muscle, and in improved glucose tolerance. These data provide evidence that exercise-training may be a viable therapeutic intervention to prevent, or at least slow the progression of fatty liver that is associated with nutrient overload.
In skeletal muscle, multiple regulatory sites for fatty acid utilization exist; amongst these is fatty acid transport across the plasma membrane. Data suggest that the transmembrane transport of fatty acid into cells involves a protein mediated transport, involving the fatty acid transporter FAT/CD36. Herein we show that FAT/CD36 is important for fatty acid uptake and oxidation during isolated muscle contractions. On the contrary, previous observations suggest that a permanent relocation of FAT/CD36 protein to the sarcolemma induces intracellular lipid accumulation, resulting in insulin resistance. Therefore, FAT/CD36 has been linked to insulin resistance. Whether increased FAT/CD36 protein at the sarcolemma is an early event in the development of decreased insulin sensitivity or whether it is a consequence of chronic oversupply of calories, increased plasma fatty acids or chronically altered metabolism is not known. We show here that a high-fat diet-induced decrease in insulin sensitivity in healthy humans is independent of a relocation or up-regulation of FAT/CD36 protein at the sarcolemma and that the accumulation of intramyocellular lipid content after a high-fat diet is independent of such an event.
| Original language | English |
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| Place of Publication | Copenhagen |
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| Publisher | Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen |
| Number of pages | 58 |
| ISBN (Print) | 978-87-7611-870-9 |
| Publication status | Published - 2015 |
