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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.
Pharmacological inhibitors of fatty acid synthase, including the approved anti-obesity drug orlistat, are shown to inhibit replication of SARS-CoV-2 in vitro and in a mouse model of infection in vivo.
Bidault et al. find that interleukin-4 activates SREBP1 to promote de novo lipogenesis that consumes NADPH to drive alternative activation of macrophages through the accumulation of reactive oxygen species.
Through integration of lipidomic and proteomic analyses of exosomes from patients with COVID-19, Lam et al. find that exosomes from different stages of infection have distinct compositions and can evoke distinct responses in recipient cells.
Boyd and LoCoco et al. link ω-6 polyunsaturated fatty acid–rich diet to development of peripheral nerve damage in mice, revealing diet as a risk factor for chronic pain.
Bile acids are shown to enter the brain and regulate short-term reductions in food intake after a meal by inhibiting neuropeptide release from agouti-related peptide/neuropeptide Y neurons.
Glycogen accumulation is a hallmark of clear cell renal cell carcinoma. Xie et al. uncover that under metabolic stress or hypoxia, these glycogen deposits are dispensable for tumour cell proliferation and survival, both in vivo and in vitro.
In a screen of peripheral blood cells from fasted or fed individuals, Han et al. identify FOXO4 and its target FKBP5 as fasting-induced modulators of CD4+ T helper cell responsiveness.
In an unbiased screen, Perry et al. find that tetracycline antibiotics improve resilience of cultured cells carrying disease-associated mitochondrial DNA mutations. Doxycycline is shown to increases survival, and reduce symptoms, in a mouse model of Leigh syndrome.
Osteoclasts are the body’s exclusive bone-resorbing cells; however, their differentiation trajectory remains unclear. Using single-cell RNA sequencing, Tsukasaki et al. provide a comprehensive road map of osteoclastogenesis, unveiling stepwise molecular events underlying osteoclast cell fate transitions.
UCP2 is shown in yeast and mammalian cells to transport aspartate out of mitochondria, thus enabling KRAS-mutated pancreatic ductal adenocarcinoma cells to perform glutaminolysis to support cancer growth.