Journal
FRONTIERS IN ENDOCRINOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fendo.2022.867929
Keywords
microRNA; hypothalamus; energy homeostasis; obesity; mice; Dicer; in situ CRISPR; Cas9 knock-out
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In this study, the researchers demonstrate the protective effect of miR-15a-5p against obesity using an in vivo reductionist approach. They also identify Bace1 as a direct target of miR-15a-5p, a gene previously linked to energy metabolism imbalance. This research provides important insights into the non-coding RNA-mediated regulation of energy homeostasis and its potential contribution to the development of novel therapeutic approaches for metabolic diseases.
Obesity is a growing medical and social problem worldwide. The control of energy homeostasis in the brain is achieved by various regions including the arcuate hypothalamic nucleus (ARH). The latter comprises a number of neuronal populations including the first order metabolic neurons, appetite-stimulating agouti-related peptide (AgRP) neurons and appetite-suppressing proopiomelanocortin (POMC) neurons. Using an in vivo reductionist approach and POMCCre-dependent CRISPR-Cas9, we demonstrate that miR-15a-5p protects from obesity. Moreover, we have identified Bace1, a gene previously linked to energy metabolism imbalance, as a direct target of miR-15a-5p. This work warrants further investigations of non-coding RNA-mediated regulation of energy homeostasis and might contribute to the development of novel therapeutic approaches to treat metabolic diseases.
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