News & Views

Metabolism regulates cell fates through the epigenome. Wang, Shi et al. demonstrate that the cell fates of pluripotency, differentiation and ageing emerge from how a nuclear protein channels metabolic fluxes into distinct epigenetic marks by regulating expression of metabolic genes.

In this issue of Nature Metabolism, Neri et al. show that two distinct stellate ganglion subcircuits innervating interscapular brown adipose tissue (iBAT) separately control thermogenesis and glucose tolerance, providing a mechanistic explanation for temperature-independent benefits of iBAT on glycaemia.

In this issue of Nature Metabolism, Sun et al. show that the kynurenine pathway of tryptophan metabolism links stress-induced impairment of immune surveillance to liver cancer progression.

Christen et al. present the first comparisons between vitamin B3 and two derivatives that are widely used in humans, showing that the vitamin B3 derivatives rely on microbiome-generated nicotinic acid to synthesize NAD⁺ and stimulate gut microbial activity.

Cachexia is a wasting disorder characterized by progressive metabolic dysregulation. A new study demonstrates using systematic multi-omics analyses that activation of one-carbon metabolism potentially contributes to energy wasting in cachexia, providing in-depth understanding of cachexia in terms of metabolic rewiring.

When the brain detects ongoing fuel depletion, sympathetic nervous system outflow to white adipose tissue induces lipolysis to mobilize fuel. Yet there exists a subset of ‘stable adipocytes’ that resist lipolysis via this mechanism. The discovery of a novel lipolysis mechanism reshapes our understanding of how body energy requirements are met in times of need.

Sex profoundly shapes liver metabolism, with oestrogens conferring protection against metabolic liver disease. In this study, Yang, Wang and colleagues identify the orphan G protein-coupled receptor GPR110 as a liver-specific brake on oestrogen signalling, bridging GPCR and nuclear receptor pathways, thus pointing to GPR110 as a target for sex-specific therapy in liver disease.

Two studies in Nature Metabolism reveal a critical role of chaperone-mediated autophagy in maintaining homeostasis and promoting regeneration of skeletal muscle.

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.

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.

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.

Oligodendrocyte progenitor cells harness aldolase C–TRPV–AMPK signalling in a bespoke way to sense glucose availability and prioritize energy towards remyelination.

Microbiota-derived metabolites shape intestinal health by modulating T cell metabolism. Li et al. show that indole-3-propionic acid (IPA) promotes mitochondrial respiration to suppress pro-inflammatory T cell differentiation, thereby alleviating inflammatory bowel disease in humans and mice.

Infant ketones during breastfeeding reprogram adipose progenitors via epigenetic modifications, driving beige fat development. This confers lifelong obesity resistance and prevents metabolic disease.

A 12-month multicentre randomized clinical trial finds that replacing added sugar in foods and beverages with sweeteners and sweetness enhancers supports modest weight loss maintenance and alters gut microbiota composition, with no safety concerns identified.

In this issue of Nature Metabolism, Wang et al. identified a non-apoptotic caspase-8 function in metabolic dysfunction-associated steatohepatitis (MASH), in which hepatocyte-derived caspase-8 induces meteorin, which in turn activates hepatic stellate cells (HSCs) to drive fibrosis. This function reveals a potential therapeutic target to directly address fibrosis and reduce the progression of metabolic dysfunction-associated steatotic liver disease (MASLD).

Cholesterol accumulation in microglia drives persistent inflammation after stroke. In this issue of Nature Metabolism, Zhao et al. suggest that enhancing microglial cholesterol catabolism may offer a promising strategy to reduce brain damage and improve recovery.

Although the gut microbiome contributes to the development of metabolic disease, beneficially altering the gut microbiome via increased fibre intake improves metabolic outcomes in rodents and humans. A new study by Jung et al. describes a novel mechanism by which the prebiotic fibre, inulin, can prevent and reverse hepatic steatosis via adaptations in the small intestinal microbiome.

In a new study, the polygenic background of type 2 diabetes (T2D) is found to determine the risk of diabetes associated with so-called monogenic forms of β-cell diabetes, as well as the age at onset and severity of diabetes.

Lactic acid activates the MondoA–TXNIP pathway, dampening CD8⁺ T cell responses and boosting regulatory T cell function. Inhibiting MondoA revives antitumour immunity and amplifies the effects of anti-PD-1 treatment.