Neuronal miR-29a protects from obesity in adult mice
Objective: Obesity, a growing threat to the modern society, represents an imbalance of metabolic queues that normally signal to the arcuate hypothalamic nucleus, a critical brain region sensing and regulating energy homeostasis. This is achieved by various neurons many of which developmentally origi...
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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Book |
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Elsevier,
2022-07-01T00:00:00Z.
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|---|---|---|---|
| 001 | doaj_8c533b024cce4a5abfb4fbffd651c7c4 | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Yuan Ma |e author |
| 700 | 1 | 0 | |a Nicola Murgia |e author |
| 700 | 1 | 0 | |a Yu Liu |e author |
| 700 | 1 | 0 | |a Zixuan Li |e author |
| 700 | 1 | 0 | |a Chaweewan Sirakawin |e author |
| 700 | 1 | 0 | |a Ruslan Konovalov |e author |
| 700 | 1 | 0 | |a Nikolai Kovzel |e author |
| 700 | 1 | 0 | |a Yang Xu |e author |
| 700 | 1 | 0 | |a Xuejia Kang |e author |
| 700 | 1 | 0 | |a Anshul Tiwari |e author |
| 700 | 1 | 0 | |a Patrick Malonza Mwangi |e author |
| 700 | 1 | 0 | |a Donglei Sun |e author |
| 700 | 1 | 0 | |a Holger Erfle |e author |
| 700 | 1 | 0 | |a Witold Konopka |e author |
| 700 | 1 | 0 | |a Qingxuan Lai |e author |
| 700 | 1 | 0 | |a Syeda Sadia Najam |e author |
| 700 | 1 | 0 | |a Ilya A. Vinnikov |e author |
| 245 | 0 | 0 | |a Neuronal miR-29a protects from obesity in adult mice |
| 260 | |b Elsevier, |c 2022-07-01T00:00:00Z. | ||
| 500 | |a 2212-8778 | ||
| 500 | |a 10.1016/j.molmet.2022.101507 | ||
| 520 | |a Objective: Obesity, a growing threat to the modern society, represents an imbalance of metabolic queues that normally signal to the arcuate hypothalamic nucleus, a critical brain region sensing and regulating energy homeostasis. This is achieved by various neurons many of which developmentally originate from the proopiomelanocortin (POMC)-expressing lineage. Within the mature neurons originating from this lineage, we aimed to identify non-coding genes in control of metabolic function in the adulthood. Methods: In this work, we used microRNA mimic delivery and POMCCre-dependent CRISPR-Cas9 knock-out strategies in young or aged mice. Importantly, we also used CRISPR guides directing suicide cleavage of Cas9 to limit the off-target effects. Results: Here we found that mature neurons originating from the POMC lineage employ miR-29a to protect against insulin resistance obesity, hyperphagia, decreased energy expenditure and obesity. Moreover, we validated the miR-29 family as a prominent regulator of the PI3K-Akt-mTOR pathway. Within the latter, we identified a direct target of miR-29a-3p, Nras, which was up-regulated in those and only those mature POMCCreCas9 neurons that were effectively transduced by anti-miR-29 CRISPR-equipped construct. Moreover, POMCCre-dependent co-deletion of Nras in mature neurons attenuated miR-29 depletion-induced obesity. Conclusions: Thus, the first to our knowledge case of in situ Cre-dependent CRISPR-Cas9-mediated knock-out of microRNAs in a specific hypothalamic neuronal population helped us to decipher a critical metabolic circuit in adult mice. This work significantly extends our understanding about the involvement of neuronal microRNAs in homeostatic regulation. | ||
| 546 | |a EN | ||
| 690 | |a Obesity | ||
| 690 | |a microRNA | ||
| 690 | |a Neuron | ||
| 690 | |a Mice | ||
| 690 | |a Hypothalamus | ||
| 690 | |a Internal medicine | ||
| 690 | |a RC31-1245 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Molecular Metabolism, Vol 61, Iss , Pp 101507- (2022) | |
| 787 | 0 | |n http://www.sciencedirect.com/science/article/pii/S221287782200076X | |
| 787 | 0 | |n https://doaj.org/toc/2212-8778 | |
| 856 | 4 | 1 | |u https://doaj.org/article/8c533b024cce4a5abfb4fbffd651c7c4 |z Connect to this object online. |