A5039071290- Dietary Effects on Health
- Diet and metabolism studies
- Adipose Tissue and Metabolism
- Immune Cell Function and Interaction
- Immune cells in cancer
- Inflammasome and immune disorders
- Protein Kinase Regulation and GTPase Signaling
- interferon and immune responses
- Cardiac electrophysiology and arrhythmias
- Cytomegalovirus and herpesvirus research
- Tryptophan and brain disorders
- Psoriasis: Treatment and Pathogenesis
- Ion channel regulation and function
- Sirtuins and Resveratrol in Medicine
- IL-33, ST2, and ILC Pathways
- Diet, Metabolism, and Disease
- Muscle metabolism and nutrition
- Adipokines, Inflammation, and Metabolic Diseases
University of Cambridge
2023-2025
National Heart Lung and Blood Institute
2023-2024
National Institutes of Health
2024
MRC Mitochondrial Biology Unit
2022
The Ohio State University Wexner Medical Center
2015
Elevated interleukin (IL)-1β levels, NLRP3 inflammasome activity, and systemic inflammation are hallmarks of chronic metabolic inflammatory syndromes, but the mechanistic basis for this is unclear. Here, we show that levels plasma IL-1β lower in fasting compared to fed subjects, while lipid arachidonic acid (AA) elevated. Lipid profiling NLRP3-stimulated mouse macrophages shows enhanced AA production an NLRP3-dependent eicosanoid signature. Inhibition cyclooxygenase by nonsteroidal...
BACKGROUNDFasting and NAD+-boosting compounds, including NAD+ precursor nicotinamide riboside (NR), confer antiinflammatory effects. However, the underlying mechanisms therapeutic potential are incompletely defined.METHODSWe explored biology in myeloid cells from healthy volunteers following vivo placebo or NR administration subsequently tested findings vitro monocytes extracted patients with systemic lupus erythematosus (SLE).RESULTSRNA-Seq of unstimulated LPS-activated implicated...
Abstract Generally, fasting and refeeding confer anti- proinflammatory effects, respectively. In humans, these caloric-load interventions function, in part, via regulation of CD4+ T cell biology. However, mechanisms orchestrating this remain incomplete. We employed integrative bioinformatics RNA sequencing high-performance liquid chromatography–mass spectrometry data to measure serum metabolites gene expression peripheral blood mononuclear cells isolated from volunteers identify...
To evaluate whether nicotinamide adenine dinucleotide-positive (NAD+) boosting modulates adaptive immunity, primary CD4+ T cells from healthy control and psoriasis subjects were exposed to vehicle or riboside (NR) supplementation. NR blunts interferon γ (IFNγ) interleukin (IL)-17 secretion with greater effects on helper (Th) 17 polarization. RNA sequencing (RNA-seq) analysis implicates blunting of sequestosome 1 (sqstm1/p62)-coupled oxidative stress. administration increases sqstm1 reduces...
Protein phosphatase 2A (PP2A) is a serine/threonine-selective holoenzyme composed of catalytic, scaffolding, and regulatory subunit. In the heart, PP2A activity requisite for cardiac excitation-contraction coupling central in adrenergic signaling. We found that mice deficient subunit B56α (1 13 subunits) had altered signaling heart was associated with changes physiology, suggesting an autoinhibitory role suppressed excess activity. The increase reduced expression resulted slower rates...
Abstract Humans have, throughout history, faced periods of starvation necessitating increased physical effort to gather food. To explore adaptations in muscle function, 13 participants (7 males and 6 females) fasted for seven days. They lost 4.6 ± 0.3 kg lean 1.4 0.1 fat mass. Maximal isometric isokinetic strength remained unchanged, while peak oxygen uptake decreased by 13%. Muscle glycogen was halved, expression electron transport chain proteins unchanged. Pyruvate dehydrogenase kinase 4...
Caloric deprivation interventions such as intermittent fasting and caloric restriction ameliorate metabolic inflammatory disease. As a human model of deprivation, 24-h fast blunts innate adaptive immune cell responsiveness relative to the refed state. Isolated serum at these time points confers same immunomodulatory effects on transformed lines. To identify mediators orchestrating this, metabolomic lipidomic analysis was performed extracted after re-feeding. Bioinformatic integration with...
NAD+ boosting via nicotinamide riboside (NR) confers anti-inflammatory effects. However, its underlying mechanisms and therapeutic potential remain incompletely defined. Here, we showed that NR increased the expression of CC-chemokine receptor 7 (CCR7) in human M1 macrophages by flow cytometric analysis cell surface receptors. Consequently, chemokine ligand 19 (CCL19, for CCR7)-induced macrophage migration was enhanced following administration. Metabolomics revealed prostaglandin E2 (PGE2)...