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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.
Folkersen et al. report the first results from the SCALLOP consortium, a collaborative framework for pQTL mapping and biomarker analysis of proteins on the Olink platform. A total of 315 primary and 136 secondary pQTLs for 85 circulating cardiovascular proteins from over 30,000 individuals were identified and replicated to yield new insights for translational studies and drug development.
Using data from 74,629 individuals from 4 independent surveys, Bonnefond et al. report a much stronger burden of pathogenic genetic variants of MODY genes among people diagnosed with type 2 diabetes than has previously been reported.
Developmental checkpoints are crucial for regulating metabolite utilization to ensure future survival. Yamada et al. use mathematical modelling to uncover a central role for ecdysteroids in regulating Drosophila larval metabolism.
Li et al. describe a new form of ATP sensing pathway that induces mitochondrial anchoring at presynaptic terminals during sustained synaptic activity. This mechanism involves AMPK–PAK energy signalling that recruits mitochondria from axons to presynaptic filamentous actin via myosin VI phosphorylation and interaction with the mitochondrial anchoring protein syntaphilin.
Using holistic and reductionist approaches, Karunakaran et al. identify a causal association between higher expression of RIPK1 (a central regulator of inflammatory cell function) and the risk of obesity. RIPK1 induces activation of proinflammatory signalling in adipose tissue, promoting the accumulation of macrophages that drive metabolic inflammation and obesity simultaneously.
Linke et al. use unbiased and quantitative techniques to directly link both known and unknown liver and plasma lipid moieties to specific genomic loci, as compiled in a public web resource, LipidGenie. LipidGenie aided in the identification of a new group of sex-specific phosphatidylcholines.
After activation, conventional T cells undergo metabolic reprogramming. de Kivit et al. show that in human thymic regulatory T cells, TNFR2 stimulation promotes a glycolytic switch with a preferential glucose-derived carbon flux into the TCA cycle to support suppressive functions.
Electron transport chain (ETC) regulation can have important consequences for cellular bioenergetics. Here, Acín-Pérez et al. show that macrophage ETC regulation by the Fgr kinase can also affect systemic metabolism in the setting of diet-induced obesity.
Pharmacological targeting of de novo lipogenesis is an attractive clinical target for a wide range of diseases. Kelly et al. report that de novo lipogenesis is essential for platelet production in primates, but not in dogs and rats.
Xia et al. provide a method for deep learning of 3D facial images to predict biological age with an accuracy of ±2.8 yr from chronological age and its correlation with lifestyle indicators and blood transcriptomic age.
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.
Carbohydrate metabolism in germ cells is shown to promote sugar appetite in female flies, thus demonstrating how metabolism in a subset of cells alters whole-animal behaviour.
Fructose consumption has greatly increased in recent years and has been linked to the development of hepatic steatosis. Here, the authors show that fructose promotes gut-barrier deterioration and subsequent endotoxaemia that in turn induces hepatic lipogenesis by activation TLR signalling in liver macrophages.
The reprogramming factor Glis1 is shown to drive cellular metabolic changes that in turn promote epigenetic alterations that facilitate induction of pluripotency.
Whereas peripheral axons regenerate well after injury, axons located in the central nervous system, such as in the spinal cord, do not. Kong et al. identify AMPK as a regulator of neuronal regeneration and show that deletion of AMPKα1 promotes regeneration of injured spinal cord axons in mice.