Hypothalamic huntingtin-associated protein 1 as a mediator of feeding behavior

Abstract

The hypothalamus responds to circulating leptin and insulin in the control of food intake and body weight. A number of neurotransmitters in the hypothalamus, including γ-aminobutyric acid (GABA), also have key roles in feeding. Huntingtin-associated protein 1 (Hap1) is expressed more abundantly in the hypothalamus than in other brain regions, and lack of Hap1 in mice leads to early postnatal death. Hap1 is also involved in intracellular trafficking of the GABAA receptor. Here, we report that fasting upregulates the expression of Hap1 in the rodent hypothalamus, whereas intracerebroventricular administration of insulin downregulates Hap1 by increasing its degradation through ubiquitination. Decreasing the expression of mouse hypothalamic Hap1 by siRNA reduces the level and activity of hypothalamic GABAA receptors and causes a decrease in food intake and body weight. These findings provide evidence linking hypothalamic Hap1 to GABA in the stimulation of feeding and suggest that this mechanism is involved in the feeding-inhibitory actions of insulin in the brain.

Cite this article

Sheng, G., Chang, Gq., Lin, J. et al. Hypothalamic huntingtin-associated protein 1 as a mediator of feeding behavior. Nat Med 12, 526–533 (2006). https://doi.org/10.1038/nm1382

View full text

>> Full Text:   Hypothalamic huntingtin-associated protein 1 as a mediator of feeding behavior