PT  - JOURNAL ARTICLE
AU  - Moura-Assis, Alexandre
AU  - Nogueira, Pedro A.
AU  - de-Lima-Junior, Jose C.
AU  - Simabuco, Fernando M.
AU  - Gaspar, Joana M.
AU  - Donato, Jose
AU  - Velloso, Licio A.
TI  - POMC-specific knockdown of Tril reduces body adiposity and increases hypothalamic leptin responsiveness
AID  - 10.1101/2020.06.25.172379
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.25.172379
4099  - http://biorxiv.org/content/early/2020/06/27/2020.06.25.172379.short
4100  - http://biorxiv.org/content/early/2020/06/27/2020.06.25.172379.full
AB  - In a public dataset of transcripts differentially expressed in selected neuronal subpopulations of the arcuate nucleus, we identified TLR4-interactor with leucine-rich repeats (Tril) as a potential candidate for mediating the harmful effects of a high-fat diet in proopiomelanocortin (POMC) neurons. The non-cell-specific inhibition of Tril in the arcuate nucleus resulted in reduced hypothalamic inflammation, protection against diet-induced obesity associated with increased whole-body energy expenditure and increased systemic glucose tolerance. The inhibition of Tril, specifically in POMC neurons, resulted in a trend for protection against diet-induced obesity, increased energy expenditure and increased hypothalamic sensitivity to leptin. Thus, Tril emerges as a new component of the complex mechanisms that promote hypothalamic dysfunction in experimental diet-induced obesity.Competing Interest StatementThe authors have declared no competing interest.