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In this study, Kagan et al. highlight the relevance of adequate cardiolipin homeostasis by offering mechanistic insight into the pathogenesis of Barth syndrome. The study shows how altered accumulation of mono-lyso-cardiolipin, one of the derivatives of the mitochondrial lipid cardiolipin, forms an anomalous peroxidase complex with cytochrome c, thus leading to increased oxidation of polyunsaturated phospholipids.
Kovatcheva et al. show that vitamin B12 improves the efficiency of in vivo reprogramming and tissue repair through its functions in one-carbon metabolism and epigenetic modulation.
Long-acting GIPR agonists, individually or as part of GIPR–GLP-1R co-agonists, are shown to require GIPR signaling in inhibitory GABAergic neurons to decrease body weight and food intake in mice.
In this study, Kreuzaler et al. perform zonal analysis to study metabolic heterogeneity in breast cancer and identify the metabolic dependency on pantothenic acid (vitamin B5) in areas of the tumor that show high expression levels of the oncogene MYC. Dietary restriction of vitamin B5 reverses several MYC-driven metabolic changes and hampers tumor progression.
In this study, Rabah et al. investigate glucose usage in the brain, and show how glial cells transfer glycolysis-derived alanine to neurons in a fly model, thus supporting memory formation in cholinergic circuits.
PDK4-dependent lactate production by senescent stromal cells is shown to promote cancer growth and drug resistance and might have a broader role in the emergence of age-associated diseases.
In this study, Fu et al. provide mechanistic insight into how GLUT2 fine-tunes environmental nutrient sensing with T cell activation, which optimizes metabolic adaptation during acquisition of T cell effector function.
Gut-derived ammonia mediates stress responses in the host by maintaining brain glutamine availability, uncovering a gut–brain signalling basis for emotional behaviour.
Bahar Halpern et al. use bulk and single-cell RNA sequencing of intestinal faecal washes to show that intestinal epithelial cells remain viable after being shed. Alongside shed immune cells, these epithelial cells may contribute to immune regulation in the intestine.
Defects in interleukin-22 production and group 3 innate lymphoid cells are correlated with aggravated gut inflammation. Wu et al. find that proline uptake via the proline transporter Slc6a7 is involved in activation of lymphoid tissue inducer cells and interleukin-22 production in the gut, and that dietary supplementation with proline alleviates colitis in a mouse model.
Guhathakurta et al. describe the acetyltransferase activity of MOF in the mitochondria. MOF can acetylate COX17, thus contributing to the assembly and function of respiratory complex IV. These findings provide better understanding of how mitochondrial function is fine-tuned by acetylation.
Miller et al. use fast thermal preservation and mass spectrometry imaging to reveal rapid neuron-layer metabolic responses to stimulation within a brain slice. Stimulation increases glucose use and converts spent ATP into metabolic fuel, via inosine.
Lundgren et al. show that in response to transient cold exposure, a distinct subpopulation of brown adipocytes carries out a lipogenic response involving production of acylcarnitines, which enables an improved thermogenic response to secondary cold exposure.
This study presents a comprehensive pipeline to profile transmembrane receptors involved in macrophage-driven inflammation in pancreatic islets during the onset of diabetes. The authors identify GPR132 as a mediator of macrophage-driven inflammation and find compounds that reduce inflammation and improve glycaemic control.
The authors develop synthetic biotics, engineered from bacteria, that could treat phenylketonuria, an inherited defect of phenylalanine (Phe) metabolism.
Yao and Gong et al. identify WD40 repeat-containing protein 6 (WDR6) to be upregulated in the liver of insulin-resistant mice. WDR6 contributes to promoting hepatic de novo lipogenesis during insulin resistance by upregulation of fatty acid synthase, and the authors identify a small molecule to inhibit this effect of WDR6 and reduce hepatic steatosis.
In young women, brain insulin action enhances peripheral insulin sensitivity, but only during the follicular phase of the menstrual cycle. This effect is absent in the luteal phase, possibly due to hypothalamic insulin resistance.
Gao et al. perform functional profiling of 60 genetic variants of glucagon-like peptide 1 receptor (GLP1R) in vitro, and link variants with impaired GLP1R cell surface expression or cAMP activation to defective insulin secretion in vitro and to impaired glucose homeostasis and adiposity in the UK Biobank.