Regulation of Satiety by Bdnf-e2-Expressing Neurons through TrkB Activation in Ventromedial Hypothalamus
Brief intro:
- Author: Pengcheng Chu, Wei Guo, He You, and Bai Lu
- Journal: Biomolecules
- Doi: https://www.doi.org/10.3390/biom13050822
- Publication Date: 2023 May 11
Products/Services used in the paper
Quotation shows PackGene:pAAV-miniCMVEGFP (PackGene) was used as the backbone to generate the AAV plasmid of e2-BDNF-Myc. The plasmid was transfected into HEK293T cells, and 48 h later, cell lysates were harvested to detect the protein expression using an anti-Myc antibody in western blot experiment. AAV2-miniCMV-e2-BDNF-Myc was packaged by PackGene.
Research Field:CNS
Animal or cell line strain:C57/B6J mice
Abstract
The transcripts for Bdnf (brain-derived neurotrophic factor), driven by different promoters, are expressed in different brain regions to control different body functions. Specific promoter(s) that regulates energy balance remain unclear. We show that disruption of Bdnf promoters I and II but not IV and VI in mice (Bdnf-e1−/−, Bdnf-e2−/−) results in obesity. Whereas Bdnf-e1−/− exhibited impaired thermogenesis, Bdnf-e2−/− showed hyperphagia and reduced satiety before the onset of obesity. The Bdnf-e2 transcripts were primarily expressed in ventromedial hypothalamus (VMH), a nucleus known to regulate satiety. Re-expressing Bdnf-e2 transcript in VMH or chemogenetic activation of VMH neurons rescued the hyperphagia and obesity of Bdnf-e2−/− mice. Deletion of BDNF receptor TrkB in VMH neurons in wildtype mice resulted in hyperphagia and obesity, and infusion of TrkB agonistic antibody into VMH of Bdnf-e2−/− mice alleviated these phenotypes. Thus, Bdnf-e2-transcripts in VMH neurons play a key role in regulating energy intake and satiety through TrkB pathway.
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