Expression of the hypothalamic transcription factor Nhlh2 is dependent on energy availability.
Mice with a deletion of the hypothalamic basic helix-loop-helix transcription factor Nhlh2 display adult onset obesity, implicating Nhlh2 in the neuronal circuits regulating energy availability. Nhlh2 colocalises with the hypothalamic thyrotrophin-releasing hormone (TRH) neurones in the paraventricular nucleus (PVN) and pro-opiomelanocortin (POMC) neurones in the arcuate nucleus. We show that Nhlh2 expression is significantly reduced in response to 24-h food deprivation in the arcuate nucleus, PVN, lateral hypothalamus, ventromedial hypothalamus (VMH) and dorsomedial hypothalamus (DMH). Food intake for 2 h following deprivation stimulates Nhlh2 expression in the arcuate nucleus and the PVN, and leptin injection following deprivation results in increased Nhlh2 expression in the arcuate nucleus, PVN, lateral hypothalamus, VMH, and DMH. Hypothalamic Nhlh2 expression in response to leptin injection is maximal by 2 h. Following leptin injection, Nhlh2 mRNA colocalises in POMC neurones in the arcuate nucleus and TRH neurones in the PVN. Nhlh2 mRNA expression in POMC neurones in the arcuate nucleus and TRH neurones in the PVN is reduced with energy deprivation and is stimulated with food intake and leptin injection. Modulation of POMC expression in response to changes in energy availability is not affected in mice with a targeted deletion of Nhlh2. However, deletion of Nhlh2 does result in loss of normal TRH mRNA expression in mice exposed to food deprivation and leptin stimulation. These data implicate Nhlh2 as a regulatory target of the leptin-mediated energy availability network of the hypothalamus, and TRH as a putative downstream target of Nhlh2.
Vella
K R
KR
Department of Veterinary and Animal Sciences, Center for Neuroendocrine Studies, University of Massachusetts, Amherst, MA, USA.
Burnside
A S
AS
Brennan
K M
KM
Good
D J
DJ
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D007031:Hypothalamus / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D011333:Pro-Opiomelanocortin; D012333:RNA, Messenger; D013973:Thyrotropin-Releasing Hormone; C484104:Nhlh2 protein, mouse