N-arachidonylglycine is a caloric state-dependent circulating metabolite which regulates human CD4+T cell responsiveness

Meadows, Allison M.; Kim, Han; Singh, Komudi; Murgia, Antonio; McNally, Ben D.; West, James A.; Huffstutler, Rebecca D.; Powell‐Wiley, Tiffany M.; Baumer, Yvonne; Griffin, Julian L.; Sack, Michael N.

doi:10.1016/j.isci.2023.106578

Cited by 4 publications

(3 citation statements)

References 67 publications

(96 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…80 N-Arachidonylglycine is a metabolite with an anti-inflammatory effect in CD4+T cells. 81 Here, we discovered that compared with the AD model group, oleoyl-Lcarnitine was highest in the 2′-FL and HMO groups (Figure 6E,F). Oleoyl-L-carnitine is a relatively potent inhibitor of GlyT2 (IC50 of 340 nM) and exhibits intriguing behavior on the transporter.…”

Section: Discussionmentioning

confidence: 69%

“…Previous investigations showed that the overall structure of oleoyl- l -carnitine was similar to N-arachidonylglycine in terms of the acyl chain (polar headgroup) but had a unique headgroup (carnitine) and an acyl chain (monounsaturated and 18-carbons long) . N-Arachidonylglycine is a metabolite with an anti-inflammatory effect in CD4+T cells . Here, we discovered that compared with the AD model group, oleoyl- l -carnitine was highest in the 2′-FL and HMO groups (Figure E,F).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Human Milk Oligosaccharides on Learning and Memory in Mice with Alzheimer’s Disease

Gao,

Fang,

Sun

et al. 2023

J. Agric. Food Chem.

View full text Add to dashboard Cite

Alzheimer's disease (AD) is distinguished by cognitive dysfunction and neuroinflammation in the brain. 2′-Fucosyllactose (2′-FL) is a major human milk oligosaccharide (HMO) that is abundantly present in breast milk and has been demonstrated to exhibit immunomodulatory effects. However, the role of 2′-FL and HMO in gut microbiota modulation in relation to AD remains insufficiently investigated. This study aimed to elucidate the preventive effect of the 2′-FL and HMO impact of AD and the relevant mechanism involved. Here, the behavioral results showed that 2′-FL and HMO intervention decreased the expression of Tau phosphorylation and amyloid-β (Aβ), inhibited neuroinflammation, and restored cognitive impairment in AD mice. The metagenomic analysis proved that 2′-FL and HMO intervention restored the dysbiosis of the gut microbiota in AD. Notably, 2′-FL and HMO intervention significantly enhanced the relative abundance of Clostridium and Akkermansia. The metabolomics results showed that 2′-FL and HMO enhanced the oleoyl-L-carnitine metabolism as potential drivers. More importantly, the levels of oleoyl-L-carnitine were positively correlated with the abundances of Clostridium and Akkermansia. These results indicated that 2′-FL and HMO had therapeutic potential to prevent AD-induced cognitive impairment, which is of great significance for the treatment of AD.

show abstract

Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Effect of Human Milk Oligosaccharides on Learning and Memory in Mice with Alzheimer’s Disease

Gao,

Fang,

Sun

et al. 2023

J. Agric. Food Chem.

View full text Add to dashboard Cite

show abstract

“… 2 In the field of T cell immunometabolism, several concepts have been added in recent years. 3 , 4 Akkaya et al. in 2018 showed that CD4 T cell activation is accompanied by a shift to glycolysis as a source of energy even in the presence of oxygen.…”

Section: Main Textmentioning

confidence: 99%

Boosting NAD: An opportunity for metabolic reprogramming of Th17 cells in psoriatic disease

Reali

2023

Cell Reports Medicine

View full text Add to dashboard Cite

Propionate functions as a feeding state–dependent regulatory metabolite to counter proinflammatory signaling linked to nutrient load and obesity

Han,

Meadows,

Rodman

et al. 2024

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Generally, fasting and refeeding confer anti- and pro-inflammatory 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-seq and HPLC-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 (GPCR) 43 (ffar2) were co-ordinately and inversely regulated by fasting and refeeding. Propionate and FFAR agonists decreased IFNγ and IL-17 and significantly blunted HDAC activity in CD4+ T cells. Furthermore, propionate blunted NFκB activity and diminished IL-6 release. In parallel, propionate reduced phosphorylation of canonical TH1 and TH17 regulators, STAT1 and STAT3, respectively. Conversely, knockdown of FFARs significantly attenuated the anti-inflammatory role of propionate. Interestingly, propionate recapitulated the blunting of CD4+ T helper 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-GPCR linked pathway to regulate CD4+ helper T cell immune responsiveness.

show abstract

N-arachidonylglycine is a caloric state-dependent circulating metabolite which regulates human CD4+T cell responsiveness

Cited by 4 publications

References 67 publications

Effect of Human Milk Oligosaccharides on Learning and Memory in Mice with Alzheimer’s Disease

Effect of Human Milk Oligosaccharides on Learning and Memory in Mice with Alzheimer’s Disease

Boosting NAD: An opportunity for metabolic reprogramming of Th17 cells in psoriatic disease

Propionate functions as a feeding state–dependent regulatory metabolite to counter proinflammatory signaling linked to nutrient load and obesity

Contact Info

Product

Resources

About