A Role for Suppressed Thermogenesis Favoring Catch-Up Fat in the Pathophysiology of Catch-Up Growth

A Role for Suppressed Thermogenesis Favoring Catch-Up Fat in the Pathophysiology of Catch-Up Growth Raffaella Crescenzo 1 , Sonia Samec 1 , Vladan Antic 1 , Francoise Rohner-Jeanrenaud 2 , Josiane Seydoux 3 , Jean-Pierre Montani 1 and Abdul G. Dulloo 1 1 Department of Medicine, Division of Physiology, University of Fribourg, Fribourg, Switzerland 2 Department of Medicine, Division of Endocrinology and Diabetology, Faculty of Medicine, University of Geneva, Geneva, Switzerland 3 Department of Physiology, Faculty of Medicine, University of Geneva, Geneva, Switzerland Abstract Catch-up growth is a risk factor for later obesity, type 2 diabetes, and cardiovascular diseases. We show here that after growth arrest by semistarvation, rats refed the same amount of a low-fat diet as controls show 1 ) lower energy expenditure due to diminished thermogenesis that favors accelerated fat deposition or catch-up fat and 2 ) normal glucose tolerance but higher plasma insulin after a glucose load at a time point when their body fat and plasma free fatty acids (FFAs) have not exceeded those of controls. Isocaloric refeeding on a high-fat diet resulted in even lower energy expenditure and thermogenesis and increased fat deposition and led to even higher plasma insulin and elevated plasma glucose after a glucose load. Stepwise regression analysis showed that plasma insulin and insulin-to-glucose ratio after the glucose load are predicted by variations in efficiency of energy use (i.e., in thermogenesis) rather than by the absolute amount of body fat or plasma FFAs. These studies suggest that suppression of thermogenesis per se may have a primary role in the development of hyperinsulinemia and insulin resistance during catch-up growth and underscore a role for suppressed thermogenesis directed specifically at catch-up fat in the link between catch-up growth and chronic metabolic diseases. Footnotes Address correspondence and reprint requests to Dr. A.G. Dulloo, Department of Medicine, Division of Physiology, University of Fribourg, Rue du Musée 5, CH-1700 Fribourg, Switzerland. E-mail: abdul.dulloo{at}unifr.ch . Received for publication 27 November 2002 and accepted in revised form 30 January 2003. AM, age-matched; FFA, free fatty acid; ME, metabolizable energy; RF, refed; WM, weight-matched. DIABETES