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By using an integrated omics approach, a landscape of metabolic remodelling of early-stage mouse embryogenesis is reconstructed, identifying key metabolites for epigenetic reprogramming.
While on a high-fat, high-calorie diet, a monthly cycle of 5 days of a fasting-mimicking diet can prevent obesity and related detrimental effects on cardiometabolic health and lifespan in mice.
Merlin et al. find that non-canonical glutamine transamination is required for macrophage efferocytosis in atherosclerotic plaques by sustaining redox buffering and fueling energy production for cytoskeletal rearrangements.
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.
Found in umami foods and known for their savoury taste, monosodium glutamate and inosine monophosphate are shown to induce metabolic syndrome in mice through induction of purine degradation in the liver and brain and through the formation of uric acid.
Patients with primary sclerosing cholangitis (PSC), a chronic cholestatic liver disease, display changes in the gut microbiota and in bile acid composition. Schneider, Candels and colleagues identify a role for microbiota-dependent regulation of bile acid synthesis through farnesoid X receptor signalling, which is relevant for PSC disease progression.
A combination of single-cell approaches, lineage tracing and metabolomics is used to characterize the changes to intestinal stem cell function in the small intestine that underlie intestinal maladaptation in mice fed an obesogenic diet.
Roy et al. quantify the impact of a high-fat diet across genetically diverse strains of mice, revealing a generally negative effect on lifespan but also a wide variability.
Cao et al. find that the mesenteric lymphatic system becomes dysfunctional during obesity in mice and humans, leading to visceral adipose tissue accumulation and insulin resistance.
Hocaoglu et al. find a conserved shift in redox metabolites in fly oocytes and mammalian cells in response to mitochondrial respiratory quiescence that leads to reprogramming of progeny metabolism.
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.
Redox signal transduction from the mitochondrial matrix to the cytosol is shown to be mediated through interaction between MIC60 and Miro, the disruption of which ameliorates oxidative stress in Drosophila.
Ji and Luo et al. show that miR-3075 in hepatocyte-derived exosomes from mice at early stages of obesity improves insulin sensitivity in chronically obese mice, while hepatocyte exosomes from chronically obese mice induce insulin resistance.
Irisin is shown to mediate beneficial effects on cognitive function associated with exercise and to improve cognitive function in mouse models of Alzheimer’s disease, probably through its direct action in the brain.
Hild et al. find that a wild-derived microbiome protects against weight gain through early postnatal metabolic programming and brown adipose tissue activation.
Multi-omics characterization of ZIKA virus–infected mouse brains reveals metabolic reprogramming events, including dysregulation of NAD+ metabolism, the correction of which is shown to alleviate ZIKA virus–induced microcephaly.
Duquenne et al. show that tanycyte leptin receptor expression is required for leptin to enter the brain and regulate peripheral lipogenesis and pancreatic β-cell function.
Puurunen et al. demonstrate the safety and tolerability in patients with phenylketonuria of a genetically modified strain of E. coli encoding metabolic enzymes to metabolize phenylalanine to non-toxic metabolites.
Salisbury et al. show that hepatic lipogenic mRNA is regulated by m6A modifications in a sex-dependent and dietary-dependent manner, contributing to sex-specific differences in hepatic lipid metabolism.