title: Role of diet and fuel overabundance in the development and progression of heart failure.
abstract: Under physiological conditions, the human heart derives energy from glucose, fatty acids, and/or lactate depending upon substrate availability, circulating hormone levels, and nutritional status. Circulating free fatty acid and glucose levels often exceed the normal range, as observed with type 2 diabetes, obesity, or physical inactivity. Chronic exposure of the heart to high plasma levels of free fatty acids may cause accumulation of toxic lipid intermediates within cardiomyocytes. Furthermore, suppression of glucose oxidation by increased fatty acid uptake shunts glucose into the oxidative pentose phosphate and hexosamine biosynthetic pathways, both of which yield potentially harmful products. Noxious derivatives of aberrant glucose and fatty acid oxidation can activate signalling cascades leading to myocyte dysfunction or death, processes termed 'glucotoxicity' and 'lipotoxicity'. This review discusses the effects of dietary extremes (e.g. high fat and high carbohydrate consumption) and substrate overabundance in the context of heart failure (HF) development and progression. Emerging data suggest that substrate excess leads to cardiac dysfunction and HF, which may be prevented or slowed by maintaining low body fat and high insulin sensitivity and consuming a diet of low glycaemic load that is high in mono- and polyunsaturated fatty acids.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Chess
authors.forename: William C
authors.initials: WC
authors.lastname: Stanley
mesh_terms: D000818:Animals; D004032:Diet; D004040:Dietary Carbohydrates / Q000009:adverse effects; D004041:Dietary Fats / Q000009:adverse effects; D018450:Disease Progression; D004435:Eating / Q000502:physiology*; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D006801:Humans
chemical_list: D004040:Dietary Carbohydrates; D004041:Dietary Fats