Deletion of MiRNA Processing Enzyme Dicer in POMC-expressing Cells Leads to Pituitary Dysfunction, Neurodegeneration and Development of Obesity

Overview

Journal Mol Metab

Specialty Cell Biology

Date 2013 Nov 8

PMID 24199146

Citations 41

Authors

Marc Schneeberger

Jordi Altirriba

Ainhoa Garcia

Yaiza Esteban

Carlos Castano

Montserrat Garcia-Lavandeira

Clara V Alvarez

Ramon Gomis

Marc Claret

Affiliations

Soon will be listed here.

Abstract

MicroRNAs (miRNAs) have recently emerged as key regulators of metabolism. However, their potential role in the central regulation of whole-body energy homeostasis is still unknown. In this study we show that the expression of Dicer, an essential endoribonuclease for miRNA maturation, is modulated by nutrient availability and excess in the hypothalamus. Conditional deletion of Dicer in POMC-expressing cells resulted in obesity, characterized by hyperphagia, increased adiposity, hyperleptinemia, defective glucose metabolism and alterations in the pituitary-adrenal axis. The development of the obese phenotype was paralleled by a POMC neuron degenerative process that started around 3 weeks of age. Hypothalamic transcriptomic analysis in presymptomatic POMCDicerKO mice revealed the downregulation of genes implicated in biological pathways associated with classical neurodegenerative disorders, such as MAPK signaling, ubiquitin-proteosome system, autophagy and ribosome biosynthesis. Collectively, our results highlight a key role for miRNAs in POMC neuron survival and the consequent development of neurodegenerative obesity.

Citing Articles

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