TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation

Author(s)

Moura-Assis, Alexandre ^{[1, 2]} ; Nogueira, Pedro A. S. ^{[1, 2]} ; de-Lima-Junior, Jose C. ^{[1, 2]} ; Simabuco, Fernando M. ^[3] ; Gaspar, Joana M. ^{[1, 2]} ; Donato Jr, Jose ; Velloso, Licio A. ^{[4, 1, 2]}

Affiliation

^[1] Univ Estadual Campinas, Lab Cell Signalling Obes, Campinas - Brazil

^[2] Univ Estadual Campinas, Comorbid Res Ctr, Campinas - Brazil

^[3] Univ Campinas UNICAMP, Sch Appl Sci FCA, Multidisciplinary Lab Food & Hlth LABMAS, Sao Paulo - Brazil

^[4] Natl Inst Sci & Technol Neuroimmunomodulat, Rio De Janeiro - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 11, n. 1 SEP 9 2021.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 18/14818-9 - Study of molecular targets important for the control of cancer metabolism: the mTOR/S6K pathway as a central role
• Grantee: Fernando Moreira Simabuco
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 17/02983-2 - The role of growth hormone in the brain: relevance for neural functions and in disease
• Grantee: Jose Donato Junior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center
• Grantee: Licio Augusto Velloso
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC