Intense Caloric Restriction from Birth Prevents Cardiovascular Aging in Rats.

We previously demonstrated that a 50% caloric restriction (CR) from birth improves several cardiometabolic risk factors in young rats. In this study, we investigated in middle-aged rats the consequences of a 50% CR from birth on cardiometabolic risk factors, heart function/morphology, ventricular arrhythmia, and fibrillation incidence, and cardiac intracellular proteins involved with redox status and cell survival. From birth to the age of 18 months, rats were divided into an Ad Libitum (AL18) group, which had free access to food, and a CR18 group, which had food limited to 50% of that consumed by the AL18. Resting metabolic rate, blood pressure, and heart rate were recorded, and oral glucose and intraperitoneal insulin tolerance tests were performed. Blood was collected for biochemical analyses, and visceral fat and liver were harvested and weighed. Hearts were harvested for cardiac function, histological, redox status, and western blot analyses. The 50% CR from birth potentially reduced several cardiometabolic risk factors in 18-month-old rats. Moreover, compared with AL18, the CR18 group showed a ∼50% increase in cardiac contractility and relaxation, nearly three to five times less incidence of ventricular arrhythmia and fibrillation, ∼18% lower cardiomyocyte diameter, and ∼60% lower cardiac fibrosis. CR18 hearts also improved biomarkers of antioxidant defense and cell survival. Collectively, these results reveal several metabolic and cardiac antiaging effects of a 50% CR from birth in middle-aged rats.

Refeeding abolishes beneficial effects of severe calorie restriction from birth on adipose tissue and glucose homeostasis of adult rats.

OBJECTIVES: Calorie restriction (CR) is an important intervention for reducing adiposity and improving glucose homeostasis. Recently we found that in rats, a severe calorie restriction (SCR) beginning at birth up to adult age promotes positive effects on cardiometabolic risk factors and heart. The aim of this study was to investigate the effects of this new model of SCR on adipose tissue and glucose homeostasis of rats and to evaluate the effects of refeeding. METHODS: From birth to 90 d of age, rats were divided into an ad libitum (AL) group, which had free access to food, and a CR50 group, which had food limited to 50% of that consumed by the AL group. From this moment, half of the CR50 animals had free access to food (the refeeding group [CR50-R]), and the other half continued 50% restricted for an additional 90-d period. Food intake was assessed daily and body weight weekly. In the final week of the SCR/refeeding protocol, oral glucose and intraperitoneal insulin tolerance tests were performed. Thereafter, rats were sacrificed and visceral fat was collected and used for histologic and Western blot analysis. RESULTS: Findings from this study revealed that SCR beginning at birth and up to adult life promoted a large decrease in visceral adiposity; improvement in glucose/insulin tolerance; and upregulation of adipose proliferating cell nuclear antigen, sirtuin 1, peroxisome proliferator-activated receptor-γ, and adiponectin. Refeeding abolished all of these effects. SCR from birth to adult age promoted beneficial effects on adipose tissue and glucose homeostasis; whereas refeeding abolished these effects.