IMR Press / FBL / Volume 12 / Issue 11 / DOI: 10.2741/2365

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article
Energy balance pathways converging on the Nhlh2 transcription factor
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1 Department of Human Nutrition, Foods and Exercise, Virginia Polytechnic Institute and State University, Corporate Research Center, 0493, RB 15, Room 1120, Blacksburg, VA 24061, USA
2 Department of Veterinary and Animal Sciences, Center for Neuroendocrine Studies and Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA 01003, USA
Front. Biosci. (Landmark Ed) 2007, 12(11), 3983–3993; https://doi.org/10.2741/2365
Published: 1 May 2007
Abstract

Multiple regulatory pathways exist to control the expression levels of neuropeptides in response to body weight and energy availability changes. Since many neuropeptides are first synthesized in a pro-neuropeptide form, the availability of processing enzymes in a neuron can control the amount of active mature neuropeptide produced at any given time. In this review, we will focus on the regulation of prohormone convertase 1 (PC1) and prohormone convertase 2 (PC2), as well as downstream neuropeptide genes. Evidence from our laboratory suggests that Nescient helix-loop-helix 2 (Nhlh2) regulates the transcription of PC1 and PC2, possibly in conjunction with the leptin-stimulated transcription factor, STAT3. Furthermore, Nhlh2 itself is a target of leptin and other energy availability signals, with high levels of expression during energy surplus, and low levels of expression in conditions of reduced energy availability such as food deprivation or cold exposure. Overall, coordinate regulation of Nhlh2, PC1, PC2 and downstream hypothalamic neuropeptides such as thyrotropin releasing hormone (TRH) and pro-opiomelanocortin (POMC) does lead to energy balance modulation and ensuing long-term changes in body weight.

Keywords
PC1
PC2
POMC
Nhlh2
TRH
Leptin
Hypothalamus
Transcription
Post-Transcriptional Processing
Review
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