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Hypothalamic bHLH transcription factors are novel candidates in the regulation of energy balance
Author(s) -
Nilaweera Kanishka N.,
Ellis Claire,
Barrett Perry,
Mercer Julian G.,
Morgan Peter J.
Publication year - 2002
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2002.01894.x
Subject(s) - neurod , leptin , medicine , endocrinology , biology , messenger rna , nucleus , gene expression , in situ hybridization , gene , transcription factor , microbiology and biotechnology , genetics , obesity
The basic helix–loop–helix transcription factors, neurological basic‐helix–loop–helix‐2 (Nhlh‐2), neurogenic differentiation‐1 (NeuroD‐1) and single minded‐1 (Sim‐1) could have roles in energy balance regulation, although supporting evidence is inconclusive. This study in mice provides further evidence that Nhlh‐2 and NeuroD‐1 are involved in energy balance regulation. In situ hybridization was used to study the expression of the genes in relation to physiological status and genetic background within hypothalamic nuclei that are involved in energy balance regulation. These studies show reduced expression of Nhlh‐2 mRNA in the arcuate (ARC) nucleus and NeuroD‐1 mRNA in the paraventricular (PVN) nucleus in obese ob/ob and 24 h food‐deprived mice relative to respective controls, suggesting regulation by leptin. Interestingly, Nhlh‐2 mRNA expression is reduced in obese db/db mice, whereas NeuroD‐1 remains unchanged, suggesting different mechanisms of regulation by leptin of these two genes. To study the role of leptin in the regulation of these genes, leptin was injected intraperitoneally in obese ob/ob mice and mRNA expression evaluated after 1 h or 4 h, or after twice‐daily injection for 7 days. None of these regimes restored Nhlh‐2 or NeuroD‐1 to wild‐type mRNA levels. These latter data suggest either that the regulation of the Nhlh‐2 and NeuroD‐1 genes by leptin is indirect or that the apparent leptin insensitivity of the gene expression reflects a developmental deficit that is a consequence of the phenotype of the obese ob / ob mice. The relationship between Nhlh‐2 and candidate energy balance‐related genes was studied by dual in situ hybridization. Nhlh‐2 mRNA was coexpressed in a subpopulation (30%) of ARC neurons expressing pro‐opiomelanocortin (POMC) mRNA, suggesting a potential functional relationship.