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

Int J Mol Sci. 2020 Nov 25;21(23):8928. doi: 10.3390/ijms21238928.


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 α (TNF-α), interleukin-6, and interleukin-1β (IL-1β) on the membrane excitability of agouti-related peptide (AgRP)- or proopiomelanocortin (POMC)-producing neurons. We found that both TNF-α and IL-1β acutely inhibited the activity of 35-42% of AgRP-producing neurons, whereas very few POMC neurons were depolarized by TNF-α. Interleukin-6 induced no acute changes in the activity of AgRP or POMC neurons. Our findings indicate that the effect of TNF-α and IL-1β, especially on the activity of AgRP-producing neurons, may contribute to inflammation-induced anorexia observed during acute inflammatory conditions.

Keywords: POMC; cytokines; inflammation; interleukin-6; obesity; sepsis.

MeSH terms

  • Agouti-Related Protein / genetics*
  • Animals
  • Anorexia / genetics
  • Anorexia / metabolism
  • Anorexia / pathology
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Arcuate Nucleus of Hypothalamus / pathology
  • Energy Metabolism
  • Humans
  • Hypothalamus / metabolism
  • Hypothalamus / pathology
  • Inflammation / genetics*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Interleukin-1beta / genetics*
  • Interleukin-6 / genetics
  • Mice
  • Neurons / metabolism
  • Neurons / pathology
  • Neuropeptide Y / genetics
  • Obesity / genetics*
  • Obesity / metabolism
  • Obesity / pathology
  • Patch-Clamp Techniques
  • Pro-Opiomelanocortin / genetics
  • Tumor Necrosis Factor-alpha / genetics*


  • Agouti-Related Protein
  • Interleukin-1beta
  • Interleukin-6
  • Neuropeptide Y
  • Tumor Necrosis Factor-alpha
  • Pro-Opiomelanocortin