In Vivo Reductionist Approach Identifies miR-15a Protecting Mice From Obesity

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.

Automated summary

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.