Dataset Information

Fasting-induced miR-7a-5p in AgRP neurons regulates food intake

ABSTRACT: The molecular control of feeding after fasting is essential for maintaining energy homeostasis, and overfeeding usually leads to obesity. RNA interference has been clinically successful in managing diseases, and the identification of a feeding-regulated microRNA (miRNA), which remains a challenge, could be a strategy for combating obesity. By performing a comprehensive genome-wide microRNA screening in the arcuate nucleus of the hypothalamus (ARC) of fasted mice and ad libitum mice, we found a significant increase in miR-7a-5p levels after fasting. miR-7a-5p was highly expressed in the ARC, and inhibition of miR-7a-5p specifically in AgRP neurons reduced food intake and body weight gain. miR-7a-5p inhibited S6K1 gene expression by binding to its 3’-UTR. Furthermore, the reduction of food intake by anti-miR-7a-5p was partially reversed by the downregulated mechanistic target of rapamycin complex 1 (mTOR1)/ribosomal S6 kinase 1 (S6K1) signaling in the AgRP neurons. Importantly, intracerebroventricular administration of the miR-7a-5p inhibitor could reduce food intake and body weight. Collectively, our findings suggest miR-7a-5p as an orexigenic factor in AgRP neurons and a potential novel target for obesity treatment.

ORGANISM(S): Mus musculus

PROVIDER: GSE254021 | GEO | 2025/01/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Neurons in the arcuate nucleus (ARC) sense the fed/fasted state and regulate hunger. ARCAgRP neurons release GABA, NPY and the melanocortin-4 receptor (MC4R) antagonist, AgRP, and are activated by fasting1-4. When stimulated, they rapidly and potently drive hunger5,6. ARCPOMC neurons, in contrast, release the MC4R agonist, α-MSH, and are viewed as the counterpoint to ARCAgRP neurons. They are regulated in an opposite fashion and their activity leads to decreased hunger2,4,7. Together, ARCAgRP and ARCPOMC neurons constitute the ARC feeding center. Against this, however, is the finding that ARCPOMC neurons, unlike ARCAgRP neurons, fail to affect food intake over the timescale of minutes to hours following opto- or chemogenetic stimulation5,8. This suggests a rapidly acting component of the ARC satiety pathway is missing. Here, we show that excitatory ARC neurons identified by expression of vesicular glutamate transporter 2 (VGLUT2) and the oxytocin receptor, unlike ARCPOMC neurons, rapidly cause satiety when chemo- or optogenetically manipulated. These glutamatergic ARC projections synaptically converge with GABAergic ARCAgRP projections on MC4R-expressing neurons in the paraventricular hypothalamus (PVHMC4R neurons), which are known to mediate satiety9. ARCPOMC neurons also send dense projections to the PVH. Importantly, the α-MSH they release post-synaptically potentiates glutamatergic synaptic activity onto PVHMC4R neurons – including that emanating from ARCVglut2 neurons. This suggests a means by which α-MSH can bring about satiety – via postsynaptic potentiation of this novel ARCVglut2 to PVHMC4R satiety circuit. Thus, while fast (GABA and NPY) and slow (AgRP) ARC hunger signals are delivered together by ARCAgRP neurons10,11, the temporally analogous satiety signals from the ARC, glutamate and α-MSH, are delivered separately by two parallel, interacting projections (from ARCVGLUT2 and ARCPOMC neurons). Discovery of this rapidly acting excitatory ARC → PVH satiety circuit, and its regulation by α-MSH, provides new insight into regulation of hunger/satiety.

Dataset Information

Fasting-induced miR-7a-5p in AgRP neurons regulates food intake

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets