TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation
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 hypothalam...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-09-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-97291-7 |
| _version_ | 1818754402417115136 |
|---|---|
| author | Alexandre Moura-Assis Pedro A. S. Nogueira Jose C. de-Lima-Junior Fernando M. Simabuco Joana M. Gaspar Jose Donato Jr Licio A. Velloso |
| author_facet | Alexandre Moura-Assis Pedro A. S. Nogueira Jose C. de-Lima-Junior Fernando M. Simabuco Joana M. Gaspar Jose Donato Jr Licio A. Velloso |
| author_sort | Alexandre Moura-Assis |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-18T05:22:41Z |
| format | Article |
| id | doaj.art-4adeb126c7c44bf4944aa30208fa4da4 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T05:22:41Z |
| publishDate | 2021-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-4adeb126c7c44bf4944aa30208fa4da42022-12-21T21:19:38ZengNature PortfolioScientific Reports2045-23222021-09-0111111410.1038/s41598-021-97291-7TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammationAlexandre Moura-Assis0Pedro A. S. Nogueira1Jose C. de-Lima-Junior2Fernando M. Simabuco3Joana M. Gaspar4Jose Donato Jr5Licio A. Velloso6Laboratory of Cell Signalling-Obesity and Comorbidities Research Center, University of CampinasLaboratory of Cell Signalling-Obesity and Comorbidities Research Center, University of CampinasLaboratory of Cell Signalling-Obesity and Comorbidities Research Center, University of CampinasMultidisciplinary Laboratory of Food and Health (LABMAS), School of Applied Sciences (FCA), University of Campinas (UNICAMP)Laboratory of Cell Signalling-Obesity and Comorbidities Research Center, University of CampinasDepartment of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao PauloLaboratory of Cell Signalling-Obesity and Comorbidities Research Center, University of CampinasAbstract 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.https://doi.org/10.1038/s41598-021-97291-7 |
| spellingShingle | Alexandre Moura-Assis Pedro A. S. Nogueira Jose C. de-Lima-Junior Fernando M. Simabuco Joana M. Gaspar Jose Donato Jr Licio A. Velloso TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation Scientific Reports |
| title | TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation |
| title_full | TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation |
| title_fullStr | TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation |
| title_full_unstemmed | TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation |
| title_short | TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation |
| title_sort | tlr4 interactor with leucine rich repeats tril is involved in diet induced hypothalamic inflammation |
| url | https://doi.org/10.1038/s41598-021-97291-7 |
| work_keys_str_mv | AT alexandremouraassis tlr4interactorwithleucinerichrepeatstrilisinvolvedindietinducedhypothalamicinflammation AT pedroasnogueira tlr4interactorwithleucinerichrepeatstrilisinvolvedindietinducedhypothalamicinflammation AT josecdelimajunior tlr4interactorwithleucinerichrepeatstrilisinvolvedindietinducedhypothalamicinflammation AT fernandomsimabuco tlr4interactorwithleucinerichrepeatstrilisinvolvedindietinducedhypothalamicinflammation AT joanamgaspar tlr4interactorwithleucinerichrepeatstrilisinvolvedindietinducedhypothalamicinflammation AT josedonatojr tlr4interactorwithleucinerichrepeatstrilisinvolvedindietinducedhypothalamicinflammation AT licioavelloso tlr4interactorwithleucinerichrepeatstrilisinvolvedindietinducedhypothalamicinflammation |