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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.
When placed in an activity-based anorexia paradigm, mice with altered AgRP circuit function recapitulate characteristics of anorexia nervosa, including a reduction in food intake, compulsive exercise and death.
Mitochondrial metabolism is critical for cardiac function and growth. Fernandez-Caggiano et al. show that maintenance of mitochondrial pyruvate transporter expression is a critical mediator of cardiac hypertrophy and heart failure.
Oncogenic cell growth and proliferation rely on aberrant activation of metabolic pathways, such as glucose fermentation, resulting in elevated cytosolic pH. Koch et al. implicate increased cytosolic pH as a driver for cell proliferation through the transcriptional activation of cyclin D1.
A single intracerebroventricular injection of FGF1 leads to a remarkable remission of diabetes in various rodent models. Here, Alonge et al. show that FGF1-induced diabetes remission in rats requires remodelling of perineuronal nets that enmesh glucoregulatory neurons in the arcuate nucleus.
Yu et al. report a preparation that enables transplantation of pancreatic islets underneath the skin and achieves long-term euglycaemia in several preclinical models of type 1 diabetes, thus providing a simple method that might enable a more widespread adoption of islet transplantation in the clinic.
The authors report the case of a young patient who displayed insulin-dependent diabetes after SARS-CoV-2 infection in the absence of autoantibodies indicative of autoimmune type 1 diabetes.
The reprogramming factor Glis1 is shown to drive cellular metabolic changes that in turn promote epigenetic alterations that facilitate induction of pluripotency.
Steinberg and colleagues show that long-chain fatty acyl-CoA esters are endogenous ligands for the drug-binding domain of AMPK β1–containing isoforms, and that such binding is critical for enhancement of fatty acid oxidation. These data may help explain how AMPK integrates responses to ketogenic diets, fasting or endurance exercise across distinct tissues in the absence of changes in adenine nucleotides.
Cancer cells rely on selenium uptake and selenocysteine biosynthesis to avoid ferroptosis. However, this mechanism makes them dependent on SEPHS2, an enzyme in the selenocysteine biosynthesis pathway for the detoxification selenide that is produced during selenocysteine formation.
Maternal exercise, before and during pregnancy, has a beneficial effect on offspring. Harris et al. report that exercise-induced release of oligosaccharide 3′-sialyllactose in mouse breast milk mediates the metabolic health benefits of maternal exercise on offspring by improving glucose and insulin tolerance and cardiac function.
Modulating the capacity of the intestinal epithelium to catabolize fructose is shown to alter fructose-induced lipogenesis in the mouse liver, suggesting that fructose clearance in the small intestine protects from steatosis.
Bayraktar et al. construct a metabolic coessentiality network to cluster metabolic genes into networks from perturbation datasets derived from 558 cancer cell lines. They identify C12orf49 as an essential component of SREBP processing and cholesterol sensing in mammalian cells.
An automated decision support system is reported that provides weekly insulin dosage recommendations to users with T1D and that, when analysing previously collected patient data, exhibits high agreement with recommendations from physicians.
Itaconate production is a hallmark of inflammatory activated macrophages. Swain et al. compare the biological effects of itaconate and its common derivatives, identifying a new regulatory mode of inhibiting IL-1β secretion and enhancing IFN-β signalling.
Tharyan et al. identify NFYB-1 as a regulator of mitochondrial function that represses lysosomal prosaposin. The NFYB-1–prosaposin signalling axis coordinates lysosomal-to-mitochondria signalling via cardiolipin to enhance cellular mitochondrial function and longevity in C. elegans.
Brett et al. demonstrate that voluntary exercise improves quiescent muscle stem cell (MuSC) function and regenerative capacity in old but not young mice through exercise-induced upregulation of Cyclin D1 and repression of TGF-β activity in quiescent MuSCs.
Low numbers of circulating CD3+CD56+ regulatory T cells are associated with reduced beta-cell function and diabetic ketoacidosis in three separate cohorts of children with type 1 diabetes.
This study establishes reciprocal regulation between the two key nutrient sensors in cells, mTORC1 and AMPK, showing that mTORC1 directly inhibits AMPK by phosphorylation at S345 in the AMPK catalytic subunit α2.