Abstract

Obesity and high-fat diet (HFD) consumption result in hypothalamic inflammation and metabolic dysfunction. While the TLR4 activation by dietary fats is a well-characterized pathway involved in the neuronal and glial inflammation, the role of its accessory proteins in diet-induced hypothalamic inflammation remains unknown. Here, we demonstrate that the knockdown of TLR4-interactor with leucine-rich repeats (Tril), a functional component of TLR4, resulted in reduced hypothalamic inflammation, increased whole-body energy expenditure, improved the systemic glucose tolerance and protection from diet-induced obesity. The POMC-specific knockdown of Tril resulted in decreased body fat, decreased white adipose tissue inflammation and a trend toward increased leptin signaling in POMC neurons. Thus, Tril was identified as a new component of the complex mechanisms that promote hypothalamic dysfunction in experimental obesity and its inhibition in the hypothalamus may represent a novel target for obesity treatment.

Details

Title
TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation
Author
Moura-Assis Alexandre 1 ; Nogueira, Pedro A, S 1 ; de-Lima-Junior, Jose C 1 ; Simabuco, Fernando M 2 ; Gaspar, Joana M 1 ; Donato Jr Jose 3 ; Velloso, Licio A 4 

 University of Campinas, Laboratory of Cell Signalling-Obesity and Comorbidities Research Center, Campinas, Brazil (GRID:grid.411087.b) (ISNI:0000 0001 0723 2494) 
 University of Campinas (UNICAMP), Multidisciplinary Laboratory of Food and Health (LABMAS), School of Applied Sciences (FCA), Limeira, Brazil (GRID:grid.411087.b) (ISNI:0000 0001 0723 2494) 
 University of Sao Paulo, Department of Physiology and Biophysics, Institute of Biomedical Sciences, Sao Paulo, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722) 
 University of Campinas, Laboratory of Cell Signalling-Obesity and Comorbidities Research Center, Campinas, Brazil (GRID:grid.411087.b) (ISNI:0000 0001 0723 2494); National Institute of Science and Technology on Neuroimmunomodulation, Rio de Janeiro, Brazil (GRID:grid.411087.b) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2570657796
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.