FEEDING DOCOSAHEXAENOIC ACID IMPAIRS HORMONAL-CONTROL OF GLUCOSE-TRANSPORT IN RAT ADIPOCYTES

High fat diets decrease glucose tolerance and increase insulin resista nce at peripheral tissues such as adipose and muscle. Fish oils, conta ining a high concentration of omega 3 fatty acids, have been reported to counter the development of insulin resistance in rats in response t o high fat diets. Because fish oils contain a number of long chain fat ty acids that may be mediating this response, we investigated the spec ific effects of docosahexaenoic acid (DHA), which comprises approximat ely 10% of the fatty acids in fish oils, on the hormonal regulation of glucose uptake in isolated adipocytes. Weanling rats were fed diets c ontaining 12% of calories as corn oil (LF-CO), or 26% of calories as s afflower oil (omega 6 rich, MF-SO) or DHASCO(TM) (44.6% DHA, MF-DHA). Feed consumption and growth did not differ between the dietary treatme nts. After 8 weeks of feeding, fasting serum glucose levels were highe r in both the high fat diet groups compared to LF-CO. Basal uptake of 2.5 mM [H-3]-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 red uced in MF-DHA rats. Decreased insulin-stimulated uptake was associate d with a reduction in total quantity of GLUT4 in MF-SO rats, but was i ndependent of any change in GLUT4 in MF-DHA fed rats. The P-adrenergic agonist, isoproterenol, decreased 2DG uptake in insulin-stimulated ad ipocytes by 51% and 36%, respectively, in the LF-CO and MF-SO groups, bur had no effect after MF-DHA feeding. This loss of P-adrenergic resp onsiveness was associated with a decrease in quantity of immunoreactiv e G alpha(s) protein. These data indicate that long-term feeding of MF -DHA diets impaired basal glucose disposal and disrupted normal hormon al regulation of glucose uptake by the adipocyte.