We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Propionate functions as a feeding state–dependent regulatory metabolite to counter proinflammatory signaling linked to nutrient load and obesity.
- Authors
Han, Kim; Meadows, Allison M; Rodman, Matthew J; Russo, Anna Chiara; Sharma, Rahul; Singh, Komudi; Hassanzadeh, Shahin; Dagur, Pradeep K; Huffstutler, Rebecca D; Krause, Fynn N; Griffin, Julian L; Baumer, Yvonne; Powell-Wiley, Tiffany M; Sack, Michael N
- Abstract
Generally, fasting and refeeding confer anti- and proinflammatory effects, respectively. In humans, these caloric-load interventions function, in part, via regulation of CD4+ T cell biology. However, mechanisms orchestrating this regulation remain incomplete. We employed integrative bioinformatics of RNA sequencing and high-performance liquid chromatography–mass spectrometry data to measure serum metabolites and gene expression of peripheral blood mononuclear cells isolated from fasting and refeeding in volunteers to identify nutrient-load metabolite-driven immunoregulation. Propionate, a short chain fatty acid (SCFA), and the SCFA-sensing G protein–coupled receptor 43 (ffar2) were coordinately and inversely regulated by fasting and refeeding. Propionate and free fatty acid receptor agonists decreased interferon-γ and interleukin-17 and significantly blunted histone deacetylase activity in CD4+ T cells. Furthermore, propionate blunted nuclear factor κB activity and diminished interleukin-6 release. In parallel, propionate reduced phosphorylation of canonical T helper 1 (TH1) and TH17 regulators, STAT1 and STAT3, respectively. Conversely, knockdown of free fatty acid receptors significantly attenuated the anti-inflammatory role of propionate. Interestingly, propionate recapitulated the blunting of CD4+ TH cell activation in primary cells from obese individuals, extending the role of this metabolite to a disease associated with low-grade inflammation. Together, these data identify a nutrient-load responsive SCFA–G protein–coupled receptor linked pathway to regulate CD4+ TH cell immune responsiveness. Propionate blunts T helper cell responsiveness.
- Subjects
SHORT-chain fatty acids; MONONUCLEAR leukocytes; T helper cells; PROPIONATES; G protein coupled receptors; DEACETYLATION
- Publication
Journal of Leukocyte Biology, 2024, Vol 115, Issue 4, p738
- ISSN
0741-5400
- Publication type
Article
- DOI
10.1093/jleuko/qiae006