Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Neurons have a high energy cost mainly sustained by glucose, but paradoxically present a weak glycolysis. This fact is now shown to account for healthy bioenergetics, reduced mitochondrial redox stress and whole-body fitness. Mice with high glycolytic rates in neurons present impaired autophagy, cognitive defects and metabolic-like syndrome.
Nguyen and Corvera review distinct changes that occur in adipose tissue during ageing, discuss potential mechanisms by which these changes impact whole-body metabolism, immunity and longevity, and highlight therapeutic opportunities.
In an attempt to investigate the role of enteroendocrine cells in the colon using elegant, targeted depletion tools, the authors of a study published in this issue of Nature Metabolism highlight the orexigenic role of a bacterial metabolite in the intestinal lumen, l-glutamate.
Agmatine produced by gut microbiota — specifically, Bacteroides vulgatus — activates the farnesoid X receptor (FXR) in intestinal epithelial L cells in a bile-acid-independent manner, which inhibits host glucagon peptide 1 (GLP-1) secretion and leads to polycystic ovary syndrome (PCOS) in mice. Supplementing mice with the GLP-1 receptor (GLP-1R) agonist liraglutide or inhibiting the production of agmatine reverses the PCOS phenotype.
A systematic deep-mutational-scanning analysis of the mitochondrial complex I assembly factor NDUFAF6 reveals its molecular function and aids in the identification of pathogenic variants in mitochondrial disease.
Diabetes can cause heart failure by a toxic accumulation of lipids in cardiac myocytes, which impairs their function. This work shows that stimulation of the bile acid receptor TGR5 limits fatty acid uptake into cardiac myocytes and prevents the development of diabetic cardiomyopathy.
Optimization of energy and carbon–nitrogen allocation maximizes the proliferation and functionality of chimeric antigen receptor (CAR)-T cells. Lakhani et al. report that tonic signalling elements (scFvs) affect CAR-T cell metabolic fitness in an antigen-independent manner. A modest carbon–nitrogen emission (overflow) and resilient metabolic phenotype (compatibility) are associated with effective CAR-T cell therapy.
In this issue of Nature Metabolism, the research team of Mitchell Lazar reveals unexpected consequences of double loss of the coregulators NCOR1 and NCOR2 (NCOR1/2) in hepatocytes of adult mice, which affects chromatin functioning and glucocorticoid receptor (GR)-mediated gene transcription.
A new engineering strategy for improving the biosynthesis of secondary metabolites in Streptomyces has been developed through the analysis of genes co-evolved with biosynthetic gene clusters. This strategy has been verified in 11 Streptomyces strains to enhance production of 16,385 metabolites, showing potential applications in drug discovery and industrial production.
Thiazolidinediones (TZDs) are potent insulin-sensitizing drugs, but their use is accompanied by adverse side-effects. Rohm et al. now report that TZD-stimulated macrophages release miR-690-containing vesicles that improve insulin sensitization and bypass unwanted side-effects.
Maternal circadian rhythms influence the health of infants. Cui, Xu and colleagues find that disruption of maternal rhythms impairs neonatal immune cell function and aggravates neonatal inflammatory disorders, which can be rescued by the administration of docosahexaenoic acid (a metabolite found in breast milk).
A new sensor that detects optoacoustic signals generated by mid-infrared light enables measurement of glucose concentration from intracutaneous tissue rich in blood. This technology does not rely on glucose measurements in interstitial fluid or blood sampling and might yield the next generation of non-invasive glucose-sensing devices for improved diabetes management.
AMPK directly phosphorylates the mitochondrial protein SYNJ2BP to facilitate its interaction with the RNA-binding protein SYNJ2a, which transports Pink1 mRNA into neurites. AMPK inhibition downstream of insulin signalling untethers Pink1 mRNA from neuronal mitochondria and favours PINK1-dependent mitophagy in neurons. ApoE4-induced insulin receptor internalization reverses the process by stabilizing Pink1 mRNA binding to neuronal mitochondria.
The mechanisms that drive cancer cachexia are unclear. Adipocyte activation of GPR81 by high levels of lactate is now shown to drive adipose tissue browning, thermogenesis and a loss of body weight in mouse models of cancer.
The mechanism by which metformin affects food intake remains controversial. Now, two studies link metformin treatment with the induction of the appetite-suppressing metabolite N-lactoyl-phenylalanine, which is produced by the intestine.
Eating requires the sensing in the stomach of not only nutrients, but also volume. A study in Nature Metabolism shows that stretch activation of PIEZO1 on X/A-like cells of the stomach reduces ghrelin production and secretion, which consequently reduces food intake.
Sharma et al. review the regulation and biological functions of apparently ‘futile’ dynamic lipid cycle in regulating whole-body metabolic homeostasis.
A recent study in Nature Metabolism uncovers a mechanism for pain sensitization that involves a regulatory protein of glycogen metabolism in spinal astrocytes. Targeting this protein, or the lactate fluxes linked to glycogen breakdown, may provide novel opportunities for pain management.
