title: Lowering body weight in obese mice with diastolic heart failure improves cardiac insulin sensitivity and function: implications for the obesity paradox.
abstract: Recent studies suggest improved outcomes and survival in obese heart failure patients (i.e., the obesity paradox), although obesity and heart failure unfavorably alter cardiac function and metabolism. We investigated the effects of weight loss on cardiac function and metabolism in obese heart failure mice. Obesity and heart failure were induced by feeding mice a high-fat (HF) diet (60% kcal from fat) for 4 weeks, following which an abdominal aortic constriction (AAC) was produced. Four weeks post-AAC, mice were switched to a low-fat (LF) diet (12% kcal from fat; HF AAC LF) or maintained on an HF (HF AAC HF) for a further 10 weeks. After 18 weeks, HF AAC LF mice weighed less than HF AAC HF mice. Diastolic function was improved in HF AAC LF mice, while cardiac hypertrophy was decreased and accompanied by decreased SIRT1 expression, increased FOXO1 acetylation, and increased atrogin-1 expression compared with HF AAC HF mice. Insulin-stimulated glucose oxidation was increased in hearts from HF AAC LF mice, compared with HF AAC HF mice. Thus lowering body weight by switching to LF diet in obese mice with heart failure is associated with decreased cardiac hypertrophy and improvements in both cardiac insulin sensitivity and diastolic function, suggesting that weight loss does not negatively impact heart function in the setting of obesity.
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Sowndramalingam
authors.initials: S
authors.lastname: Sankaralingam
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada Faculty of Pharmacy, Yarmouk University, Irbid, Jordan.
authors.forename: Osama
authors.initials: O
authors.lastname: Abo Alrob
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Liyan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jagdip S
authors.initials: JS
authors.lastname: Jaswal
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Cory S
authors.initials: CS
authors.lastname: Wagg
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Arata
authors.initials: A
authors.lastname: Fukushima
authors.affiliation: Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Raj S
authors.initials: RS
authors.lastname: Padwal
authors.affiliation: Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: David E
authors.initials: DE
authors.lastname: Johnstone
authors.affiliation: Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Arya M
authors.initials: AM
authors.lastname: Sharma
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada gary.lopaschuk@ualberta.ca.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Lopaschuk
mesh_terms: D000818:Animals; D004041:Dietary Fats; D005227:Fatty Acids / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D054144:Heart Failure, Diastolic / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D010084:Oxidation-Reduction; D015398:Signal Transduction / Q000502:physiology; D015431:Weight Loss
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D007328:Insulin