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POMC-specific knockdown of Tril reduces body adiposity and increases hypothalamic leptin responsiveness

Moura-Assis, A.; de Lima-Junior, J. C.; Nogueira, P. A.; Simabuco, F. M.; Gaspar, J. M.; Junior, J. D.; Velloso, L. A.

2020-06-27 neuroscience
10.1101/2020.06.25.172379 bioRxiv
Show abstract

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.

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