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Jing et al. show that COVID-19 infection causes white adipose tissue (AT) browning in mice and hamsters, which is mediated by VEGF action in the AT. VEGF blockade can ameliorate browning phenotype and COVID-19-induced weight loss, potentially providing a strategy to treat infection-induced AT atrophy.
Itaconate is a metabolite with immune-modulatory effects in myeloid cells. In this study, Zhao, Teng et al. report an additional role for itaconate in CD8+ T cells, with implications for immune surveillance and anti-tumour immunity.
Rahbani et al. show that the α1-adrenergic receptor potentiates thermogenesis in thermogenic adipocytes, acting via Gαq signalling, creatine kinase B and tissue-non-specific alkaline phosphatase.
Wolfson et al. show that microbial hydrogen sulfide contributes to the nonenzymatic reduction of azo xenobiotics, which include food dyes and drugs. This modulates sulfur homeostasis, xenobiotic metabolism and the chemical landscape of the gut.
Understanding dynamic metabolic changes in complex biological samples often overlooks heterogeneity in cell composition. Wang et al. combine mass spectrometry imaging, isotope tracing, and multiplexed immunofluorescence microscopy to study metabolic dynamics in the kidney upon ischemia–reperfusion.
A single transfer of blood from old male mice is shown to induce cellular and tissue senescence in young animals, unless old mice are treated with senolytic drugs before blood exchange.
The key regulator of lysosomal biogenesis, Tfeb, is shown to directly induce Irg1 transcription and mitochondrial itaconate production to restrain bacterial growth in macrophages.
Itaconate is an immunomodulatory macrophage metabolite. Mesaconate, a structurally similar molecule, is shown to be synthesized from itaconate in inflammatory macrophages and shows similar immunomodulatory effects, despite not repressing tricarboxylic acid cycle activity nor inhibiting succinate dehydrogenase activity.
The immunomodulatory effects of mesaconate and citraconate, naturally occurring isomers of the immunomodulatory metabolite itaconate, are investigated. Mesaconate is shown to be derived from itaconate, and citraconate is shown to inhibit ACOD1 and display stronger NRF2 agonism.
Patients with diabetes are more susceptible to suffer from more severe COVID-19. Tong et al. identify a glucose-like metabolite that is reduced in patients with diabetes and has the ability to prevent cellular infection by SARS-CoV-2
Haddad-Tóvolli et al. show that food craving-like episodes in pregnant mice result from a reorganization of the dopaminergic mesolimbic circuitry, and can have long-lasting negative metabolic and neuropsychological effects on the offspring.
Gomes, Ilter, Low et al. show that alterations in propionate metabolism contribute to cancer aggressiveness through the accumulation of the by-product methylmalonic acid.
Wanner et al. demonstrate SARS-CoV-2 liver tropism and identify transcriptional and proteomic profiles of SARS-CoV-2 liver samples that show similarities to previously characterized hepatotropic viruses.
Zhao et al. uncouple the effects of body temperature and metabolic rate on lifespan in two rodent models, showing that in warm conditions, where body temperature is elevated and metabolic rate reduced, lifespan is reduced. Reversal of increased body temperature reverses the negative impact of high ambient temperatures on lifespan despite lowered metabolic rate.
Fujimaki et al. show that soluble Dll4 from endothelial cells triggers atrophy in myofibres via Notch2 signalling, suggesting Dll4 as a therapeutic target for muscle atrophy.
Using a combination of metabolomics and bacterial and host genetics, Pruss et al. show that upregulated oxidative ornithine metabolism in Clostridioidesdifficile promotes its persistence within the gastrointestinal tract under non-inflammatory conditions.