The ventral hypothalamus acts to integrate visceral and systemic information to control energy balance. The basic helix loop helix transcription factor Neurogenin 3 (Ngn3) is required for pancreatic beta cell development, and has been implicated in neuronal development in the hypothalamus. Here, we demonstrate that early embryonic hypothalamic inactivation of Ngn3 in mice results in rapid post-weaning obesity that is associated with hyperphagia and reduced energy expenditure. This obesity is caused by loss of expression of Pomc in Pomc/Cart neurons in the arcuate nucleus, indicating an incomplete specification of anorexigenic first order neurons. Furthermore, following the onset of obesity both the arcuate and ventromedial hypothalamic nuclei become insensitive to peripheral leptin treatment. This conditional mouse mutant therefore represents a novel model system for obesity associated with hyperphagia and under activity, and sheds new light upon the roles of Ngn3 in the specification of hypothalamic neurons controlling energy balance.
- Received January 22, 2013.
- Accepted April 24, 2013.
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