Feeding docosahexaenoic acid impairs hormonal control of glucose transport in rat adipocytes

High fat diets decrease glucose tolerance and increase insulin resistance at peripheral tissues such as adipose and muscle. Fish oils, containing a high concentration of ω3 fatty acids, have been reported to counter the development of insulin resistance in rats in response to high fat diets. Because fish oils contain a number of long chain fatty acids that may be mediating this response, we investigated the specific effects of docosahexaenoic acid (DHA), which comprises approximately 10% of the fatty acids in fish oils, on the hormonal regulation of glucose uptake in isolated adipocytes. Weanling rats were fed diets containing 12% of calories as corn oil (LF-CO), or 26% of calories as safflower oil (ω6 rich, MF-SO) or DHASCO ™ (44.6% DHA, MF-DHA). Feed consumption and growth did not differ between the dietary treatments. After 8 weeks of feeding, fasting serum glucose levels were higher in both the high fat diet groups compared to LF-CO. Basal uptake of 2.5 mM [ 3 H]-2-deoxyglucose (2DG) was reduced in MF-DHA compared to LF-CO. Insulin stimulated 2-DG uptake in all three diet groups. However, despite this stimulus, uptake was lower in MF-SO rats and further reduced in MF-DHA rats. Decreased insulin-stimulated uptake was associated with a reduction in total quantity of GLUT4 in MF-SO rats, but was independent of any change in GLUT4 in MF-DHA fed rats. The β-adrenergic agonist, isoproterenol, decreased 2DG uptake in insulin-stimulated adipocytes by 51% and 36%, respectively, in the LF-CO and MF-SO groups, but had no effect after MF-DHA feeding. This loss of β-adrenergic responsiveness was associated with a decrease in quantity of immunoreactive Gα s protein. These data indicate that long-term feeding of MF-DHA diets impaired basal glucose disposal and disrupted normal hormonal regulation of glucose uptake by the adipocyte.