The effects of high fat diet on function, metabolism and insulin signaling in the rat heart
12 / 2002 - 12 / 2006
Metabolic overstimulation by overfeeding may result in functional and structural changes of the cardiovascular system, as well as in alterations of cellular metabolic and signaling pathways. In particular, overfeeding may result in ectopic triglyceride accumulation, which has been implicated in the pathophysiologic mechanisms underlying insulin resistance. In addition, pathological accumulation of lipids in non-adipose tissues, including the heart and the pancreatic beta-cell, may induce the functional and structural changes of these organs as observed in type 2 diabetes. The causative mechanisms may involve steatosis-induced changes in the insulin receptor (IR) signaling pathway and the ensuing modulation of transcription factor activity. In the diabetic heart, excessive lipid deposition may cause changes in insulin signaling and substrate (glucose and fatty acids) utilization leading to an altered energy metabolism and ultimately, functional abnormalities. In this pilot study we intend to study the effects of a high fat (HF) diet on myocardial function, lipid accumulation and insulin signaling in rats. Cardiac function will be studied in the isolated right ventricular papillary muscle of overfed rats, and compared with cardiac function in control rats (low fat (LF) diet). The ultimate goal is to elucidate the mechanisms underlying the development of cardiac dysfunction in insulin resistant states such as obesity and type 2 diabetes. Furthermore, in future experiments using this model, antisteatotic agents such as peroxisome proliferator-activated receptor (PPAR) gamma or alpha receptor agonists will be evaluated with regard to their proposed beneficial effects on cardiac metabolism and function.