Effects of rapid or slow body weight reduction on glucose tolerance during equivalent weight loss in rats fed high-fat diet

Abstract

Excess accumulation of visceral fat induces insulin resistance in skeletal muscle and impairs glucose tolerance. Although weight loss improves glucose tolerance by reducing visceral fat mass, the effects of the speed of weight loss on glucose metabolism are unclear. This study compared the effects of long-term energy restriction–induced weight loss and short-term fasting–induced weight loss on glucose tolerance in rats fed a high-fat diet. After 2 weeks of high-fat diet feeding, male Wistar rats were subjected to either 30% calorie restriction for 2 weeks (CR) or 3-day fasting (FAST). After the intervention period, body weight and intra-abdominal fat mass decreased to a similar extent in both weight-loss groups. The maximum insulin-stimulated glucose uptake and GLUT-4 content in the epitrochlearis muscle were significantly higher in the FAST group than in both control rats fed ad libitum (CON) and the CR group, with no significant differences between the CON and CR groups. Blood glucose levels during the oral glucose tolerance test (OGTT) were similar in the CON and CR groups, but insulin levels were significantly lower in the CR group than in the CON group, indicating improved insulin resistance in the CR group. However, compared to the CON and CR groups, plasma glucose and insulin levels were significantly higher and lower, respectively, in the FAST group during the OGTT. These findings suggest that rapid weight loss through short-term fasting, in contrast to long-term energy restriction, may impair glucose tolerance by reducing insulin secretion capacity.