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The antidiabetic drug acarbose is shown to be degraded by a Klebsiella species present in the human gut, which is enriched with acarbose treatment and might mediate acarbose resistance and variations in clinical efficacy observed in patients.
Results from a randomized clinical trial show that adding exercise to diet-induced weight loss can improve beta-cell function, measured as late-phase disposition index, in people with newly diagnosed type 2 diabetes.
Elevated plasma branched-chain amino acid (BCAA) levels have been associated with insulin resistance and type 2 diabetes. Blair et al. show that altering BCAA oxidation in skeletal muscle or liver does not influence insulin sensitivity in male mice, despite the effects on BCAA plasma levels.
In this study, Hu et al. identify a new mechanism through which sirtuin-4 fine-tunes urea cycle flux through decarbamylation of ornithine transcarbamylase to ensure proper ammonia detoxification upon increased amino acid catabolism.
Studies of the physiological effects of metabolites often rely on injections of metabolite salts. In this study, Lund et al. show that the hypertonicity of the injected solutions can drive the metabolic effects attributed to pharmacological administration of lactate. This work highlights the importance of taking treatment osmolarity and counterions into account in the experimental design.
Wang et al. identify a promoter variant in xanthine oxidoreductase associated with diabetic kidney disease through increased podocyte depletion and glomerular injury.
Human and mouse cells expressing a redox-insensitive GAPDH mutant that otherwise retains its catalytic activity are shown to be unable to upregulate the oxidative pentose phosphate pathway in response to oxidative stress.
Wunderling et al. develop a fatty acid tracing technology based on alkyne-labelled fatty acids and directly demonstrate triglyceride cycling in 3T3-L1 adipocytes, which allows maintenance and modification of stored fatty acid pools.
In this study, Green, Marttila, Kiweler et al. characterize one-carbon metabolism rewiring in response to a dual MTHFD1 and MTHFD2 inhibitor. This work provides insight into one-carbon fluxes, and reveals a previously uncharacterized vulnerability in cancer cells created by folate trapping.
Mi, Qi et al. identify a mechanism through which defective oxidative phosphorylation in astrocytes deregulates astroglial lipid homeostasis and subsequently impacts neurons and microglial cells, thus triggering neuronal damage and microglial reactivity.
The authors identify a high-pH-activated chloride channel as a taste receptor responsible for the avoidance of alkaline foods in fruit flies, laying the groundwork for future research on alkaline taste sensation in other animals.
Human mutations in PCYT2 result in severe pathology with failure to thrive and progressive degenerative disease. Cikes et al. demonstrate that loss of PCYT2-synthesized phosphatidylethanolamines in muscle impairs sarcolemmal lipid bilayer stability and mitochondrial homeostasis, leading to muscle degeneration and premature ageing in mice.
Doke et al. show that NMN and NR supplementation has protective effects on kidney injury by preventing cisplatin-induced release of cytosolic mitochondrial RNA and subsequent activation of the RIG-I pathway and inflammation.
Sympathetic innervation of brown and white adipose tissue is shown to be promoted by zinc released from thermogenic adipocytes, revealing a positive feedback mechanism for regulation of thermogenesis and thereby energy expenditure.
Senescenct cells are shown to accumulate cholesterol in lysosomes, which upregulates mTORC1 signaling, thereby supporting the senescence-associated secretory phenotype and promoting senescence-associated inflammation.
Takhaveev et al. use single-cell methods and mathematical modeling to reveal distinct waves in the synthesis rates of proteins, lipids and polysaccharides during the budding yeast cell cycle and relate them to flux changes in primary metabolism.
How obesity contributes to COVID-19 severity is not fully understood. In this study, Yoshiji et al. found that the plasma protein nephronectin partially mediates the effect of obesity on the risk of COVID-19 severity using a two-step Mendelian randomization approach and omics analyses.
Schilperoort et al. explore the mechanisms underlying dynamic changes in macrophage metabolism that support efferocytosis. They show that transient glycolysis and subsequent lactate production are necessary to execute continual efferocytosis, as opposed to prolonged glycolysis observed in pro-inflammatory macrophages.
The authors provide evidence in mice and humans showing that parenteral nutrition impairs glucose and insulin homeostasis by altering the gut microbiota and its metabolites.