LPS induces rapid increase in GDF15 levels in mice, rats, and humans but is not required for anorexia in mice

Am J Physiol Gastrointest Liver Physiol. 2022 Feb 1;322(2):G247-G255. doi: 10.1152/ajpgi.00146.2021. Epub 2021 Dec 22.

Abstract

Growth differentiation factor 15 (GDF15), a TGFβ superfamily cytokine, acts through its receptor, cell line-derived neurotrophic factorfamily receptor α-like (GFRAL), to suppress food intake and promote nausea. GDF15 is broadly expressed at low levels but increases in states of disease such as cancer, cachexia, and sepsis. Whether GDF15 is necessary for inducing sepsis-associated anorexia and body weight loss is currently unclear. To test this we used a model of moderate systemic infection in GDF15KO and GFRALKO mice with lipopolysaccharide (LPS) treatment to define the role of GDF15 signaling in infection-mediated physiologic responses. Since physiological responses to LPS depend on housing temperature, we tested the effects of subthermoneutral and thermoneutral conditions on eliciting anorexia and inducing GDF15. Our data demonstrate a conserved LPS-mediated increase in circulating GDF15 levels in mouse, rat, and human. However, we did not detect differences in LPS-induced anorexia between WT and GDF15KO or GFRALKO mice. Furthermore, there were no differences in anorexia or circulating GDF15 levels at either thermoneutral or subthermoneutral housing conditions in LPS-treated mice. These data demonstrate that GDF15 is not necessary to drive food intake suppression in response to moderate doses of LPS.NEW & NOTEWORTHY Although many responses to LPS depend on housing temperature, the anorexic response to LPS does not. LPS results in a potent and rapid increase in circulating levels of GDF15 in mice, rats, and humans. Nevertheless, GDF15 and its receptor (GFRAL) are not required for the anorexic response to systemic LPS administration. The anorexic response to LPS likely involves a myriad of complex physiological alterations.

Keywords: GDF15; GFRAL; LPS; anorexia; thermoneutrality.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anorexia / metabolism*
  • Eating / drug effects
  • Growth Differentiation Factor 15 / drug effects*
  • Growth Differentiation Factor 15 / metabolism*
  • Humans
  • Lipopolysaccharides / pharmacology*
  • Mice
  • Nausea / chemically induced
  • Rats
  • Weight Loss / drug effects

Substances

  • Growth Differentiation Factor 15
  • Lipopolysaccharides