Effects of dietary history on energy metabolism and physiological parameters in C57BL/6J mice

Abstract

New Findings: • What is the central question of this study? Do intake patterns of diets with a different energy content have a lasting effect on body weight persistence? • What is the main finding and its importance? After switches between semi-purified diets differing only in the fat-to-sugar ratio, the last consumed diet determined the energy intake, energy expenditure, body weight, body fat stores, circulating hormones and metabolites in C57BL/6J mice. In contrast with persistent effects observed in studies using diets with different ingredients, suggesting diet-induced set points, this study shows that body weight and metabolic parameters 'settle' based on current energetic input and output. This supports the settling point theory and underlines the importance of the choice of diet in physiological studies. Understanding body weight regulation is essential to fight obesity. Mouse studies, using different types of diets, showed conflicting results in terms of body weight persistence after changing from an ad libitum high-fat diet to an ad libitum low-fat diet. In this study, we questioned specifically whether the energy content of the diet has a lasting effect on energy balance and body weight, using multiple switches and two purified diets with a different fat-to-sugar ratio, but otherwise identical ingredients. Young-adult obesity-prone male C57BL/6J mice were fed single or double switches of semi-purified diets with either 10 energy % (en%) fat (LF) or 40en% fat (HF), with starch replaced by fat, while protein content remained equal. After none, one or two dietary changes, energy metabolism was assessed at 5, 14 and 19 weeks. We observed no systematic continuous compensation in diet and energy intake when returning to LF after HF consumption. Body weight, white adipose tissue mass and histology, serum metabolic parameters, energy expenditure and substrate usage all significantly reflected the current diet intake, independent of dietary changes. This contrasts with studies that used diets with different ingredients and showed persistent effects of dietary history on body weight, suggesting diet-dependent metabolic set points. We conclude that body weight and metabolic parameters 'settle', based on current energetic input and output. This study also highlights the importance of considering the choice of diet in physiological and metabolic intervention studies. © 2013 The Authors. Experimental Physiology © 2013 The Physiological Society.