Rapid development of cardiac dysfunction in a canine model of insulin resistance and moderate obesity

Abstract

Aims/hypothesis The worldwide incidence of obesity and diabetes continues to rise at an alarming rate. A major cause of the morbidity and mortality associated with obesity and diabetes is heart disease, yet the mechanisms that lead to cardiovascular complications remain unclear. Methods We performed cardiac MRI to assess left ventricular morphology and function during the development of moderate obesity and insulin resistance in a well-established canine model (n=26). To assess the influence of dietary fat composition, we randomised animals to a traditional lard diet (rich in saturated and monounsaturated fat; n=12), a salmon oil diet (rich in polyunsaturated fat; n=8) or a control diet (n=6). Results High-fat feeding with lard increased bodyweight and fasting insulin and markedly reduced insulin sensitivity. Lard feeding also significantly reduced left ventricular function, evidenced by a worsening of circumferential strain and impairment in left ventricular torsion. High-fat feeding with salmon oil increased bodyweight; however, salmon oil feeding did not impair insulin sensitivity or cardiac function. Conclusions/interpretation These data emphasise the importance of dietary fat composition on both metabolic and cardiac function, and have important implications for the relationship between diet and health.

Insulin Access to Skeletal Muscle is Preserved in Obesity Induced by Polyunsaturated Diet

“…Previously published findings after six weeks in each diet condition reported that plasma insulin was significantly increased from baseline from 50.4 ± 7.7 to 60.4 ± 10.7 pmol/L in LARD animals, whereas the SO intervention caused no significant changes in insulin (34.6 ± 6.8 to 31.0 ± 4.3 pmol/L) . Similarly, in these longer studies, we found that LARD feeding, but not SO feeding, induced plasma hyperinsulinemia at basal insulin levels in both artery and vein (Figure A‐B).…”

“…The acute effects of 6 weeks of LARD and SO diets on SI and cardiac function have been reported previously . The present study reports data on extended diet durations of 3.0 ± 0.3 months of LARD feeding and 3.9 ± 0.1 months of SO feeding.…”

Of mice (dogs) and men: getting to the heart of obesity-associated cardiac dysfunction

“…Rather than attempting such direct comparisons, a more synergistic interpretation may be helpful. Two theories clearly extend from the work by Broussard et al [21] in concert with other recent human and animal investigations: (1) using appropriately sensitive measurement techniques, such as motion-sensitive MRI, cardiac mechanics of the LV are impaired in the setting of obesity; and (2) insulin resistance is a critical element—at least as one of several potentially causative or intermediary factors—in the linkage between obesity and heart disease. The immediate knowledge gaps that extend from these theories are then fairly straightforward: (1) what is the long-term prognostic significance of reduced cardiac mechanics in obese patients; and (2) can therapeutically targeting insulin signalling pathways positively impact the adverse effects of obesity on the heart?…”

“…In the current issue of Diabetologia , Broussard et al add to this collective experience with animal models of obesity and contribute interesting new insights [21]. Using a canine model of moderate obesity induced by lard-based high-fat feeding, the authors observed LV systolic dysfunction (i.e.…”

“…It is instinctive, and easy given the direct compatibility of MRI measurements between animals and humans, to directly extrapolate from studies like that of Broussard et al [21] and others [16, 17] to human disease, but such an exercise is fraught with challenges. For example, while reduced cardiac mechanics in animals are generally consistent with findings in human studies, the details of reduced circumferential strain and torsion are subject to debate, as some human studies have found no change [12] or even increases [13] in those specific measures.…”