title: Calorie restriction attenuates cardiac remodeling and diastolic dysfunction in a rat model of metabolic syndrome.
abstract: Calorie restriction (CR) can modulate the features of obesity-related metabolic and cardiovascular diseases. We have recently characterized DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of metabolic syndrome. DS/obese rats develop hypertension and manifest left ventricular remodeling and diastolic dysfunction, as well as increased cardiac oxidative stress and inflammation. We have now investigated the effects of CR on cardiac pathophysiology in DS/obese rats. DS/obese rats were fed either normal laboratory chow ad libitum or a calorie-restricted diet (65% of the average food intake for ad libitum) from 9 to 13 weeks. Age-matched homozygous lean (DahlS.Z-Lepr(+)/Lepr(+) or DS/lean) littermates served as controls. CR reduced body weight in both DS/obese and DS/lean rats, as well as attenuated the development of hypertension in DS/obese rats without affecting blood pressure in DS/lean rats. CR also reduced body fat content, ameliorated left ventricular hypertrophy, fibrosis, and diastolic dysfunction, and attenuated cardiac oxidative stress and inflammation in DS/obese rats. In addition, it increased serum adiponectin concentration, as well as downregulated the expression of angiotensin-converting enzyme and angiotensin II type 1A receptor genes in the heart of DS/obese rats. Our results thus show that CR attenuated obesity and hypertension, as well as left ventricular remodeling and diastolic dysfunction in DS/obese rats, with these latter effects being associated with reduced cardiac oxidative stress and inflammation.
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, 1-1-20 Daikominami, Higashi-ku, Nagoya 461-8673, Japan. nagata@met.nagoya-u.ac.jp.
authors.forename: Miwa
authors.initials: M
authors.lastname: Takatsu
authors.forename: Chieko
authors.initials: C
authors.lastname: Nakashima
authors.forename: Keiji
authors.initials: K
authors.lastname: Takahashi
authors.forename: Tamayo
authors.initials: T
authors.lastname: Murase
authors.forename: Takuya
authors.initials: T
authors.lastname: Hattori
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ito
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Kohzo
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D031204:Caloric Restriction; D004195:Disease Models, Animal; D006321:Heart / Q000503:physiopathology*; D006973:Hypertension / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D020303:Rats, Inbred Dahl; D011924:Rats, Zucker; D020257:Ventricular Remodeling / Q000502:physiology*
keywords: angiotensin system; calorie restriction; cardiac remodeling, ventricular; diastolic heart failure; hypertension; inflammation; metabolic syndrome; oxidative stress; renin