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

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.

Hypothalamic neuroinflammation induced by obesity and the effect of Liraglutide ‎

“…Studies also showed that the glial cells are particularly affected by saturated fatty acids (SFAs) diet due to heterogeneity and neurogenic neuroinflammation during degenerative conditions [41]. More significantly, neonatal high-fat diet feeding seems to raise plasma glucose levels associated with microglial activation in the hypothalamus in weeks [42,43]. Indeed, reactive morphological and functional changes that characterized microglia activation increase inflammatory cytokines, nitric oxide, and reactive oxygen species (ROS).…”