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Neurons are shown to use fatty acid β-oxidation as a fuel source for memory formation upon intensive learning in Drosophila, challenging the view that neurons are unable to use fatty acids for energy production.
Dietary restriction promotes the expansion of effector T cells via ketone bodies, which enhances anti-tumour immunity and synergizes with immunotherapy in mice.
The microbial metabolite trimethylamine (TMA), the precursor of TMAO, which is associated with adverse cardiometabolic outcomes, is shown to have beneficial metabolic and anti-inflammatory effects in the host in the context of obesity.
A machine-learning-based computational approach to probe pathway coessentiality reveals that complex II of the electron transport chain regulates de novo purine synthesis, and can be targeted to treat acute myeloid leukaemia.
Two studies in Nature Metabolism reveal a critical role of chaperone-mediated autophagy in maintaining homeostasis and promoting regeneration of skeletal muscle.
Age-related decline of chaperone-mediated autophagy blunts the regenerative capacity of muscle stem cells, partly due to impaired glycolytic shift required for normal stem cell expansion.
Chaperone-mediated autophagy declines with age in skeletal muscle of humans and mice, leading to muscle dysfunction characterized by impaired calcium homoeostasis and mitochondrial function.
We show that the size of the mitochondrial NAD+ pool in hepatocytes is regulated by SLC25A51 expression in vivo. We further find that selectively increasing mitochondrial NAD+ is sufficient to improve liver regeneration after partial hepatectomy, equivalent to the effect of systemic high-dose NAD+ precursor supplementation.
This Review highlights how metabolic interactions between microglia and neurons shape brain health, and how their disruption in ageing and disease contributes to cognitive decline.
Modulating mitochondrial NAD+ levels by changing the expression of the mitochondrial NAD+ transporter, SLC25A51, Mukherjee et al. demonstrate that mitochondrial, rather than cytosolic or nuclear, NAD+ levels are a key determinant of the rate of liver regeneration.
In a mouse model of the rare disease citrin deficiency, the authors discovered that the accumulation of glycerol-3-phosphate leads to ChREBP activation and FGF21 induction. The study identifies glycerol-3-phosphate as a ChREBP-activating ligand, which could resolve paradoxes of FGF21 expression and clarify the logic of lipogenic transcription.
A uridine-sensitized CRISPR-Cas9 screening identifies demethoxy-CoQ as an alternative electron acceptor in the absence of CoQ, and NUDT5 as a regulator of de novo pyrimidine synthesis via its interaction with PPAT.
The question of why muscle wasting persists in cancer cachexia despite adequate nutrition has long since intrigued researchers. Here, the authors identify PDE4D-mediated suppression of cAMP–PKA–CREB1 signalling as a driver of mitochondrial dysfunction and show that PDE4D inhibition preserves muscle bioenergetics and mass in cancer cachexia.
Tumour-induced dysregulation of cAMP–PKA–CREB1 signalling in skeletal muscle is shown to be a driver of mitochondrial dysfunction, contributing to cancer cachexia in mice.
A new study in mice links ethanol consumption to endogenous fructose generation via hepatic aldose reductase, which enhances alcohol-seeking behaviour and liver damage. Inhibition of ketohexokinase reduced these effects, highlighting potential targets for managing alcohol use disorders.
Children born to mothers with type 1 diabetes (T1D) are less likely to develop T1D than those with an affected father or sibling. We identified modifications of DNA methylation at multiple T1D risk genes in blood samples from children exposed to maternal T1D. These changes were linked to decreased islet autoimmunity risk.
Through an epigenome-wide blood analysis in children of mothers with or without type 1 diabetes, the authors identify epigenetic modifications of type 1 diabetes susceptibility loci through which maternal type 1 diabetes may protect from islet autoimmunity in offspring.
By parsing stimulus-responsive sources of astrocytic reactive oxygen species (ROS), Barnett et al. reveal how mitochondrial complex III-derived signals uniquely shape inflammatory responses and astrocyte–neuron crosstalk, linking mitochondrial redox cues to dementia-related neurodegeneration.
