Low-protein diet blocks development of hyperphagia and obesity in rats with hypothalamic knife cuts

The objective of this study was to examine the influence of dietary protein levels on development of hyperphagia and obesity in rats that had been given surgical knife cuts between the ventromedial and lateral areas of the hypothalamus. Under normal conditions, rats with this type of surgery exhibit hyperphagia and become obese when given unlimited access to dietary energy. Earlier studies indicated impaired adaptive diet-induced thermogenesis in response to excess energy intake in this animal model of obesity. Because low protein diets can also stimulate diet-induced thermogenesis, we conducted four experiments which examined how diets containing different levels of protein affect development of hyperphagia and obesity in female rats given bilateral, parasagittal wire knife cuts between the ventromedial and lateral areas of the hypothalamus. For 28 d, knife-cut and sham-operated rats were given unlimited or restricted (1 79 or 1 80 kJ/d) access to diets containing protein at 5, 10 or 20% of total metabolizable energy. Knife-cut rats with unlimited access to 10 or 20% protein diets became obese, gaining 2-3 times more weight and 3-6 times more carcass energy while consuming 55-89% more energy than sham-operated rats. In contrast, energy consumed and gained by knife-cut rats with unlimited access to a 5% protein diet was similar to that of rats given sham surgery. Results indicate that a low protein diet effectively blocks development of hyperphagia and obesity in rats with surgical knife cuts between the ventromedial and lateral regions of the hypothalamus.