High fat/high fructose diet results in diastolic dysfunction in young C57Bl6/J female mice

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 758-779-Cardiometabolic Risk & Vascular Biology
Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-772
Camila Manrique*, Vincent DeMarco, Annayya Aroor, Javad Habibi, Irina Mugerfeld and James R Sowers
University of Missouri, Columbia, MO
BACKGROUND: Cardiovascular disease (CVD) constitutes the main source of morbidity and mortality in the type 2 diabetic (DM2) population. Premenopausal women exhibit less CVD compared to age-matched men. Nonetheless, women have an increased occurrence of CVD when diabetic in comparison with DM2 men. Heart failure is one of the manifestations of diabetic CVD, and diastolic dysfunction is an early finding. Obesity, a common finding in the setting of DM2, has a more deleterious impact in the left ventricle of women. METHODS: The present study examines the effect on insulin sensitivity and cardiac function of 8 weeks of high fructose/high sucrose (HF/HS) diet in young C57Bl6/J male and female mice. The HF/HS diet consisted of 60% fat and 20% sucrose. Animals were fed for 8 weeks. Parallel control groups were fed regular chow. At the end of the intervention period, rodents underwent hyperinsulinemic-euglycemic clamps and 2-D echocardiograms. Statistical significance was explored using 2-way ANOVA. RESULTS: Male mice were significantly heavier than females in both feeding paradigms. HF/HS diet only resulted in a higher weight in male rodents (p<0.05). In parallel, percentage of body fat was significantly increased in the male rodents fed with HF/HS (WDM) diet but not in females (WDF). Aldosterone levels were higher in females compared with males (p <0.05), but were not affected by HF/HS diet (p > 0.05). Glucose infusion rate (GIR) at steady-state was significantly higher in the female mice fed on control diet (CDF) when compared to male mice fed control diet (CFM). HF/HS diet resulted in insulin resistance in both male and female mice. Indexes of diastolic and systolic function were assessed. Myocardial performance index, which assess global cardiac function, was increased upon feeding with HF/HS diet in both sexes, but its impact was greater in females (p<0.05). WDF exhibit significantly more pronounced diastolic dysfunction at this age than their male counterparts when propagation velocity and isovolumic relaxation time were assessed. CONCLUSION: Young female C57Bl6/J mice are not protected from over-nutrition-induced insulin resistance. Furthermore, diastolic dysfunction manifests earlier in female rodents. The present data suggest a predisposition toward developing diabetic cardiomyopathy in females exposed to a western-like diet, which might be correlated with high aldosterone levels in females.

Disclosure: JRS: Advisory Group Member, Merck & Co.. Nothing to Disclose: CM, VD, AA, JH, IM

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Acknowledgements: Hyperinsulinemic-hyperglymic clamps were performed at Vanderbilt University School of Medicine Mouse Metabolic Phenotyping Center.   Funding:  This research was supported by NIH (R01 HL73101-01A and R01 HL107910-01) and the Veterans Affairs Merit System (0018) for JRS.