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Diabetic Hearts Feel The Burn

Date:
November 26, 2007
Source:
Journal of Clinical Investigation
Summary:
A normal heart burns both fats and sugars for fuel. In contrast, diabetic hearts rely almost exclusively on fats for energy, leading to heart failure. PPAR-alpha and PPAR-beta/delta are proteins found in heart tissue. In the diabetic heart, enhanced activity of PPAR-alpha drives the use of fats as fuel, but the role of PPAR-beta/delta has been unknown.
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A normal heart burns both fats and sugars for fuel. In contrast, diabetic hearts rely almost exclusively on fats for energy, leading to heart failure. PPAR-alpha and PPAR-beta/delta are proteins found in heart tissue.

In the diabetic heart, enhanced activity of PPAR-alpha drives the use of fats as fuel, but the role of PPAR-beta/delta has been unknown. While seeking to understand the role of these proteins in diabetic heart failure, Daniel Kelly and his colleagues at Washington University School of Medicine, Missouri, have discovered that selective activation of PPAR-beta/delta in the heart improves cardiac function in mice.

The heart of mice in which PPAR-alpha is engineered to be overexpressed only in the heart (MHC-PPAR-alpha mice) has been shown to mimic the diabetic heart -- with increased fat and decreased sugar fuel usage, and subsequent cardiac arrest.

In contrast, in this study, the hearts of mice engineered to overexpress PPAR-beta/delta only in the heart (MHC-PPAR-beta/delta mice) were shown to process sugars for energy and had function normally.

Most strikingly, the degree of heart tissue death following heart attack was reduced in MHC-PPAR-beta/delta mice compared with both normal mice and MHC-PPAR-alpha mice.

Researchers also uncovered a reason for these observed differences -- the two proteins have opposite effects on the genes responsible for sugar usage by the heart for fuel. The authors therefore suggested that heart-specific PPAR-beta/delta activation might be a useful therapy for reducing diabetes-induced heart disease in humans.

Journal article: Nuclear receptors PPAR-beta/delta and PPAR-alpha direct distinct metabolic regulatory programs in the mouse heart, Journal of Clinical Investigation,  November 21, 2007


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Journal of Clinical Investigation. "Diabetic Hearts Feel The Burn." ScienceDaily. ScienceDaily, 26 November 2007. <www.sciencedaily.com/releases/2007/11/071121172254.htm>.
Journal of Clinical Investigation. (2007, November 26). Diabetic Hearts Feel The Burn. ScienceDaily. Retrieved May 22, 2015 from www.sciencedaily.com/releases/2007/11/071121172254.htm
Journal of Clinical Investigation. "Diabetic Hearts Feel The Burn." ScienceDaily. www.sciencedaily.com/releases/2007/11/071121172254.htm (accessed May 22, 2015).

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