A pathway for how insulin signaling in the mouse hypothamalus ― a region of the brain known to control food intake ― is involved in obesity is presented in this week's Nature Medicine. The findings could lead to a new therapeutic model for obesity intervention and weight loss treatment.
In struggling with weight gain, one approach is to eat less food. However, reducing food intake leads to a natural decrease in the amount of energy used, and this consequently contributes to a relapse of obesity. Various hormones, such as insulin, play a key regulatory role in the process of food intake and energy expenditure.
Insulin is known to inhibit food intake through FoxO1, a transcription factor, in hypothalamic neurons. Domenico Accili and colleagues observed that by significantly reducing the amount of FoxO1 in the hypothalamus, mice would reduce their food intake without also decreasing their energy use. They also show that FoxO1 in the hypothalamus inversely impacts the local concentration of Cpe, an enzyme that is required for the proper maturation of key hormones that also regulate food intake. An independent experiment where Cpe was over-expressed showed that this enzyme protected mice from weight gain without changing energy use, confirming the relationship between FoxO1 and Cpe.
The separation of food intake from energy spending allows for new therapeutic possibilities in obesity.
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