Leptin receptor-positive and leptin receptor-negative proopiomelanocortin neurons innervate an identical set of brain structures

Author(s)

Lima, Leandro B. ; Metzger, Martin ; Furigo, Isadora C. ; Donato, Jr., J.

• Document type: Journal article
• Source: Brain Research; v. 1646, p. 366-376, SEP 1 2016.
• Web of Science Citations: 7

Abstract

Neurons that express the prohormone proopiomelanocortin (POMC) in the arcuate hypothalamic nucleus (Arc) are engaged in the regulation of energy balance and glucose homeostasis. Additionally, POMC neurons are considered key first-order cells regulated by leptin. Interestingly, in the Arc, POMC cells that express the leptin receptor (POMC/LepR+ cells) are found side by side with POMC cells not directly responsive to leptin (POMC/LepR- cells). However, it remains unknown whether these distinct populations innervate different target regions. Therefore, the objective of the present study was to compare the projections of POMC/LepR+ and POMC/LepR- neurons. Using genetically modified LepR-reporter mice to identify leptin receptor-expressing cells and immunohistochemistry to stain POMC-derived peptides (alpha-MSH or beta-endorphin) we confirmed that approximately 80% of Arc beta-endorphin-positive neurons co-expressed leptin receptors. POMC/LepR+ and POMC/LepR- axons were intermingled in all of their target regions. As revealed by confocal microscopy, we found an elevated degree of co-localization between alpha-MSH+ axons and the reporter protein (tdTomato) in all brain regions analyzed, with co-localization coefficients ranging from 0.889 to 0.701. Thus, these two populations of POMC neurons seem to project to the same set of brain structures, although one of the two subtypes of POMC axons was sometimes found to be more abundant than the other in distinct subregions of the same nucleus. Therefore, POMC/LepR+ and POMC/LepR- cells may target separate neuronal populations and consequently activate distinct neuronal circuits within some target nuclei. These findings contribute to unravel the neuronal circuits involved in the regulation of energy balance and glucose homeostasis. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 15/10992-6 - Investigation of metabolic programming through different approaches
• Grantee: Jose Donato Junior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/18086-0 - Molecular basis of leptin resistance
• Grantee: Jose Donato Junior
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 12/02388-3 - Topography and transmitter phenotype of the projections between the lateral habenula, the rostromedial tegmental nucleus and the dorsal raphe nucleus in the rat
• Grantee: Martin Andreas Metzger
• Support Opportunities: Regular Research Grants