High Fat Feeding in Mice Is Insufficient to Induce Cardiac Dysfunction and Does Not Exacerbate Heart Failure

Abstract

Preclinical studies of animals with risk factors, and how those risk factors contribute to the development of cardiovascular disease and cardiac dysfunction, are clearly needed. One such approach is to feed mice a diet rich in fat (i.e. 60%). Here, we determined whether a high fat diet was sufficient to induce cardiac dysfunction in mice. We subjected mice to two different high fat diets (lard or milk as fat source) and followed them for over six months and found no significant decrement in cardiac function (via echocardiography), despite robust adiposity and impaired glucose disposal. We next determined whether antecedent and concomitant exposure to high fat diet (lard) altered the murine heart’s response to infarct-induced heart failure; high fat feeding during, or before and during, heart failure did not significantly exacerbate cardiac dysfunction. Given the lack of a robust effect on cardiac dysfunction with high fat feeding, we then examined a commonly used mouse model of overt diabetes, hyperglycemia, and obesity (db/db mice). db/db mice (or STZ treated wild-type mice) subjected to pressure overload exhibited no significant exacerbation of cardiac dysfunction; however, ischemia-reperfusion injury significantly depressed cardiac function in db/db mice compared to their non-diabetic littermates. Thus, we were able to document a negative influence of a risk factor in a relevant cardiovascular disease model; however, this did not involve exposure to a high fat diet. High fat diet, obesity, or hyperglycemia does not necessarily induce cardiac dysfunction in mice. Although many investigators use such diabetes/obesity models to understand cardiac defects related to risk factors, this study, along with those from several other groups, serves as a cautionary note regarding the use of murine models of diabetes and obesity in the context of heart failure.

Obesity induced by high fat diet attenuates postinfarct myocardial remodeling and dysfunction in adult B6D2F1 mice

“…These results are further supported by the lack of effect of HFD on vasorelaxation response to acetylcholine or NO, or on arterial pressure, that remained stable throughout the study. Globally, our data are in agreement with recent studies [16,17,[33][34][35], that failed to document a role of diet-induced obesity in the development of heart remodeling and failure. Since hyperglycemia activates the cardiac intracellular renin-angiotensin system, which increases oxidative stress and cardiac fibrosis [36], the absence of hyperglycemia in our model could explain the preservation of function and heart morphology.…”

Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration

“…All strains exhibited a similar degree of functional impairment 3 d after injury, indicating a similar degree of infarction. At 1 month, ejection fraction had significantly worsened in SJL and stabilized in C57Bl/6, as in many past observations 14,23 . In contrast, the two high-MNDCM strains (A and SWR) showed improved function at day 28 compared to immediately after injury (Fig.…”

MicroRNA-539 Is Up-regulated in Failing Heart, and Suppresses O-GlcNAcase Expression

“…Echocardiographic Assessment-Transthoracic echocardiography of the left ventricle was performed as previously described (16,21,22). Body temperature was maintained at 36.5-37.5°C using a rectal thermometer interfaced with a servo-controlled heat lamp throughout the procedure.…”