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Effect of Behavioral Interventions on Insulin Sensitivity and Atherosclerosis in the Watanabe Heritable Hyperlipidemic Rabbit

From the Departments of Psychology (J.A.G., A.S., J.P., C.C., M.M.L., N.S., P.M.M), Medicine (A.M., R.B.G.), and Pathology (J.Z.), University of Miami, Coral Gables, and the University of Miami School of Medicine, Miami, FL; and the Department of Neurobiology and Physiology (J.E.L.), Northwestern University, Evanston, IL.

Address correspondence and reprint requests to Philip M. McCabe, PhD, Department of Psychology, University of Miami, P.O. Box 248185, Coral Gables, FL 33124. E-mail: pmccabe{at}miami.edu

Objective: A previous study suggested that insulin metabolic variables play a role in the progression of atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. The present study sought to determine: 1) if young, individually caged WHHLs are insulin-resistant relative to New Zealand white (NZW) rabbits and 2) whether dietary or exercise interventions can improve insulin sensitivity and slow the development of atherosclerosis in these animals.

Methods: Forty-two WHHLs were assigned to a dietary, exercise, or control condition, and 12 NZWs were used as a comparison control group. The intervention ran from 3 to 7 months of age, and all animals received an intravenous glucose tolerance test at the beginning and end of the intervention.

Results: WHHLs were insulin-resistant relative to NZWs at 3 months of age. Whereas the dietary intervention was effective in controlling insulin resistance, WHHLs in the exercise group without dietary restriction and the control group exhibited significant increases in insulin resistance. No intervention significantly influenced the progression of atherosclerosis.

Conclusions: Young WHHLs are insulin-resistant during an early period when atherosclerosis is developing rapidly. Dietary restriction, but not exercise without weight control, is effective in controlling insulin metabolic variables in the WHHL model. Although dietary intervention can reduce cardiovascular risk factors such as insulin resistance, it is not effective in slowing the development of atherosclerosis in these genetically dyslipidemic animals. Similarly, exercise training, without dietary control, does not influence the progression of disease in WHHLs.

Key Words: diet • exercise • insulin resistance • WHHL rabbit • atherosclerosis

Abbreviations: WHHL = Watanabe heritable hyperlipidemic rabbit; VLDL = very-low-density lipoprotein; LDL = low-density lipoprotein; HDL = high-density lipoprotein; NZW = New Zealand white rabbit; IVGTT = intravenous glucose tolerance test; HOMA = Homeostasis Model Assessment; CV = coefficient of variation; SBP = systolic blood pressure; MAP = mean arterial pressure; DBP = diastolic blood pressure; HR = heart rate; BMI = body mass index; CNS = central nervous system.

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