Lipoproteins abnormalities in obese insulin-resistant dogs.

Many studies have shown that obesity and low insulin sensitivity are associated with lipoprotein abnormalities, which are risk factors for coronary heart disease. The effects of insulin resistance on lipoprotein metabolism were investigated in hyperenergetic-fed beagle dogs, a new model of insulin resistance. Insulin resistance was assessed by the 3-hour euglycemic-hyperinsulinemic glucose clamp technique. Lipoproteins were separated by fast-protein liquid chromatography (FPLC) and lipid composition of the different lipoproteins was determined by enzymatic methods. Hyperenergetic diet was associated with a 43% +/- 5% increase in dog body weight and a reduction in insulin-mediated glucose uptake (28 +/- 3 to 16 +/- 1 mg. kg(-1). min(-1), P <.05). Low insulin sensitivity associated with obesity was related to an increase in plasma triglyceride (TG) through an increase in very-low-density lipoprotein (VLDL)-TG (0.071 +/- 0.020 v 0.382 +/- 0.242 mmol/L, P <.05) and high-density lipoprotein (HDL)-TG (0.025 +/- 0.012 v 0.242 +/- 0.143 mmol/L, P <.05). Other lipid abnormalities common in insulin resistant humans were also found: lower plasma HDL-cholesterol (4.690 +/- 0.151 v 3.937 +/- 0.141 mmol/L, P <.05) and higher plasma nonesterified fatty acids (NEFA) (0.974 +/- 0.094 v 1.590 +/- 0.127 mmol/L, P <.05) levels. These data show that this model of the insulin-resistant obese dog could be useful in studying insulin resistance-associated dyslipidemia.