Development of Obesity is Associated with Increased Calories per Meal Rather than per Day. A Study of High-Fat Diet-Induced Obesity in Young Rats

Abstract

We challenge the current belief that obesity is a result of overnutrition by studying a rodent model of human obesity. Male Sprague-Dawley rats at 3 weeks of age were fed with a mixed normal diet of 10% fat and high-fat diet of 60% fat (50:50) for 2 weeks and then turned to 100% high-fat diet until 43 weeks of age. Body weight gain was recorded, and food intake, eating behavior, and metabolic variables were measured by a comprehensive laboratory animal monitoring system. Body composition was determined by dual-energy X-ray absorptiometry. Ghrelin/obestatin-producing A-like cells in the stomach were analyzed by immunohistochemistry. Rats on high-fat diet were overweight at 9 weeks of age and later became obese characterized by increased body weight and excess fat deposition. There were no obesity-prone, obesity middle tertile, and obesity-resistant subgroups in rats on high-fat diet. The young rats on high-fat diet, even before becoming overweight (i.e., 8 weeks), consumed larger portion of meal (kilocalorie per meal) and ate faster but less frequent than the rats on normal diet. Obese rats had reduced food intake (expressed as gram per 100-g body weight per 24 h), unchanged calorie intake (kilocalorie per 100-g body weight per 24 h), and energy expenditure (kilocalorie per hour per 100-g body weight), and increased number of A-like cells in the stomach. Large size of meal, but not overnutrition, appears to be responsible for high-fat diet-induced obesity in rats. We propose a consideration that prevention strategies for obesity epidemic should strongly focus on meal size at early childhood and adolescence.