Tumor Necrosis Factor alpha and Interleukin-1 beta Acutely Inhibit AgRP Neurons in the Arcuate Nucleus of the Hypothalamus

Author(s)

Chaves, Fernanda M. ^[1] ; Mansano, Naira S. ^[2] ; Frazao, Renata ^[2] ; Donato Jr, Jose

Affiliation

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, BR-05508000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Anat, BR-05508900 Sao Paulo - Brazil

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 21, n. 23 DEC 2020.
• Web of Science Citations: 0

Abstract

Obesity-associated low-grade inflammation favors weight gain, whereas systemic infection frequently leads to anorexia. Thus, inflammatory signals can either induce positive or negative energy balance. In this study, we used whole-cell patch-clamp to investigate the acute effects of three important proinflammatory cytokines, tumor necrosis factor alpha (TNF-alpha), interleukin-6, and interleukin-1 beta (IL-1 beta) on the membrane excitability of agouti-related peptide (AgRP)- or proopiomelanocortin (POMC)-producing neurons. We found that both TNF-alpha and IL-1 beta acutely inhibited the activity of 35-42% of AgRP-producing neurons, whereas very few POMC neurons were depolarized by TNF-alpha. Interleukin-6 induced no acute changes in the activity of AgRP or POMC neurons. Our findings indicate that the effect of TNF-alpha and IL-1 beta, especially on the activity of AgRP-producing neurons, may contribute to inflammation-induced anorexia observed during acute inflammatory conditions. (AU)

• FAPESP's process: 20/01318-8 - Central nervous system as a target of growth hormone for the regulation of multiple biological functions
• Grantee: Jose Donato Junior
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 17/21840-8 - Growth hormone signaling in the brain as a mediator of puberty and fertility
• Grantee: Renata Frazão
• Support type: Regular Research Grants
• FAPESP's process: 17/22189-9 - Does the factors that change food intake modulate the activity of Kiss1 neurons?
• Grantee: Naira da Silva Mansano
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/21854-9 - Investigation of pro- and anti-inflamatory cytokines in biophysical properties of POMC and AgRP neurons of the arcuate nucleus of the hypothalamus
• Grantee: Fernanda Machado Chaves
• Support type: Scholarships in Brazil - Doctorate
• 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 type: Research Projects - Thematic Grants