Cardiac and metabolic changes in long-term high fructose-fat fed rats with severe obesity and extensive intramyocardial lipid accumulation

Abstract

Metabolic syndrome and obesity-related diseases are affecting more and more people in the Western world. The basis for an effective treatment of these patients is a better understanding of the underlying pathophysiology. Here, we characterize fructose- and fat-fed rats (FFFRs) as a new animal model of metabolic syndrome. Sprague-Dawley rats were fed a 60 kcal/100 kcal fat diet with 10% fructose in the drinking water. After 6, 12, 18, 24, 36, and 48 wk of feeding, blood pressure, glucose tolerance, plasma insulin, glucose, and lipid levels were measured. Cardiac function was examined by in vivo pressure volume measurements, and intramyocardial lipid accumulation was analyzed by confocal microscopy. Cardiac AMP-activated kinase (AMPK) and hepatic phosphoenolpyruvate carboxykinase (PEPCK) levels were measured by Western blotting. Finally, an ischemia-reperfusion study was performed after 56 wk of feeding. FFFRs developed severe obesity, decreased glucose tolerance, increased serum insulin and triglyceride levels, and an initial increased fasting glucose, which returned to control levels after 24 wk of feeding. The diet had no effect on blood pressure but decreased hepatic PEPCK levels. FFFRs showed significant intramyocardial lipid accumulation, and cardiac hypertrophy became pronounced between 24 and 36 wk of feeding. FFFRs showed no signs of cardiac dysfunction during unstressed conditions, but their hearts were much more vulnerable to ischemia-reperfusion and had a decreased level of phosphorylated AMPK at 6 wk of feeding. This study characterizes a new animal model of the metabolic syndrome that could be beneficial in future studies of metabolic syndrome and cardiac complications.

Impaired contractile recovery after low-flow myocardial ischemia in a porcine model of metabolic syndrome

“…Reduced activities of AMPK and PDH have been observed in the myocardium in models of insulin resistance and/or high-fat feeding (1,9,25,51), and reduced activity of either enzyme exacerbates myocardial contractile dysfunction after ischemia and reperfusion (29,44). However, in the present model, we found no evidence that either assigned diet or ischemia-reperfusion influenced the phosphorylation of AMPK, PDH activity, or expression of the major PDH regulatory kinases PDK2 and PDK4 in the myocardium.…”

Potential link between excess added sugar intake and ectopic fat: a systematic review of randomized controlled trials

“…Additionally, animal studies have observed that fructose intake may play a role in the development of local fat depots. [55][56][57] To date, however, no study in humans has examined the effects of sugar on local ectopic depots, including such sites as the kidney, pancreas, heart, and blood vessels.…”

Metformin Prevents the Development of Chronic Heart Failure in the SHHF Rat Model

“…LV samples were prepared according to Axelsen et al (24). Protein concentrations were determined by the BCA Protein Assay Kit (Pierce Biotechnology) using BSA as a standard.…”