Date of Award

2-24-2004

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Psychology

First Advisor

Holly Brown-Borg

Abstract

Obesity is influenced by dietary consumption of fat while much of the population consumes a diet deficient of the trace mineral copper. Obesity and copper deficiency can alter cardiovascular function; including cardiac hypertrophy, increased myocyte lipid droplet volume, and cardiac contractile depression. Interestingly, lipotoxic dysfunction is characterized by many of the same mechanistic alterations that are observed in obesity and copper deficiency. Additionally, the sphingolipid ceramide is elevated in lipotoxic dysfunction. However, functional leptin:leptin receptor signaling prevents lipotoxic dysfunction. The purpose of my dissertation was to determine the role of a high fat and marginal copper deficient diet on cardiac contractile function in isolated ventricular myocytes and to assess the role of lipotoxic dysfunction.

Weanling, Sprague Dawley rats (n = 10/group) were fed diets containing: 10% of calories (C) from fat and adequate copper (6 mg/kg diet); 10% of C from fat and marginally deficient copper (1.5 mg/kg diet); 45% of C from fat and adequate copper; or 45% of C from fat and marginal copper. After 12 weeks, animals were decapitated and hearts were extracted. Contractile characteristics of enzymatically isolated cardiac myocytes were determined using an lon Optix MyoCam® edge detection system. Protein abundance of SERCA2a, PLB, iNOS, eNOS, and nitrotyrosines were determined by Western blotting; ceramide was quantified using the diacylglycerol kinase assay and apoptosis was assessed by the TUNEL assay.

High fat fed rats developed significantly elevated body weights and hyperleptinemia while diet consumption was reduced, suggesting leptin-induced early satiety. Marginally copper deficient animals displayed reduced kidney copper concentrations. Furthermore, depressed myocyte peak shortening (PS), in the absence of concomitant hypertension or diabetes, was observed in animals fed either the high fat and/or marginally copper deficient diets. There was no difference in tissue ceramide level or the number of TUNEL positive cells between the groups. Protein abundance of PLB was increased suggesting this may play a role in depressed myocyte PS. Therefore, animals fed high fat and/or marginally copper deficient diets develop cardiac contractile dysfunction in the absence of lipotoxic dysfunction, possibly due to functional leptin:leptin receptor signalling.

Download

Share

COinS