Fish Oil Prevents Insulin Resistance Induced by High-Fat Feeding in Rats
REDUCED POTENCY OF INSULIN ACTION, or insulin resistance, is a feature of non-insulin-dependent diabetes mellitus (1). The influence of diet on insulin action in target tissues such as muscle, adipose, and liver is poorly understood, but the high fat intake in the Western style diet is considered a major contributor to a number of disease states. These include not only diabetes but also heart disease and obesity (2), and direct links between insulin resistance, diabetes, and the development of obesity have been suggested (3, 4). The type of dietary fat is thought to be important in this regard, and much work has focused on saturated compared to unsaturated fats (5). Recently, great interest has been generated by studies showing a reduced incidence of heart disease in men eating as little as 30 g of fish per day (6). Further, fish oils (which are high in long-chain polyunsaturated -3 fatty acids) have a hypolipidemic effect in normal subjects (7) and result in a marked lowering of triglycerides in the blood of subjects with type IIb and type V hypertriglyceridemia (8). The close relation between hyperlipidemia and insulin resistance and the surprisingly low prevalence of non-insulin-dependent diabetes in Eskimos (9), whose diet consists largely of fish, led us to examine whether long-chain polyunsaturated -3 fatty acids can protect against the development of impaired insulin action.
Earlier we showed that feeding rats diets high in fat (safflower oil) leads to a major and widespread impairment of insulin action compared to feeding them high-carbohydrate diets (4, 10). We now report that replacing as little as 6% of the linoleic -6 fatty acids from safflower oil with long-chain polyunsaturated -3 fatty acids from fish oil can prevent the development of insulin resistance in rats.
Insulin action was assessed by the euglycemic clamp technique combined with bolus administration of [3H]2-deoxyglucose and [14C]glucose to determine insulin-mediated glucose metabolic rate and glycogen synthesis rate in individual tissues (10-14). In the present experiments, 36 adult male Wistar rats (60 2 days of age) that were reared on laboratory chow under controlled conditions (21| 1|C, 12:12 lighting cycle with lights on at 0600) were randomly chosen and assigned to three groups of 12. (All data are reported as mean SEM.) These were fed for 31 1 days (i) on laboratory chow (Allied) containing (in percentage of calories) 65% carbohydrate, 12% fat, and 23% protein (chow group); (ii) on a high-fat diet containing 59% fat (from safflower oil), 10% carbohydate, and 21% protein (fat group); or (iii) on the high-fat diet but with 20% of the safflower oil replaced with extracted tuna oil (fish group). The tuna oil contained 13% eicosapentaenoic acid and 16% docosahexaenoic acid, the two main -3 fatty acids by analysis with gas-liquid chromatography. The actual change from the fat to fish diets thus represented the replacement of approximately 6% of the safflower fatty acids with long-chain polyunsaturated -3 fatty acids. The intakes of the fat and...