Figure 1. Pomc deletion in the hypothalamus leads to obesity in ad libitum fed mice.

Bumaschny and colleagues demonstrated that the restoration of hypothalamic Pomc expression could normalize body weight in young mice, but this is progressively attenuated as obesity was allowed to continue and the age of Pomc restoration was delayed. When Pomc-deficient mice were aged on a calorie-restricted diet, later Pomc reexpression prevented the subsequent development of obesity, suggesting that the preceding development of obesity, but not age itself, is responsible for the attenuated phenotypic responses to Pomc rescue in older Pomc-deficient mice.