News & Views

A recent study published in Nature Metabolism finds that the co-occurrence of chronic diseases, rather than any single condition, drives the progressive deterioration of glycaemic control in older adults, reframing glucose management as a multimorbidity-informed challenge.

In this issue of Nature Metabolism, Diotallevi et al. propose a novel non-canonical function of inducible nitric oxide synthase (iNOS) as a regulator of immune-responsive gene 1 (IRG1, also known as ACOD1) enzymatic activity and the IRG1 protein interactome.

In this issue of Nature Metabolism, Brain, Vigil et al. show that NRF2-induced cystine uptake drives the formation of several cysteine–sugar metabolites. This process acts as a ‘sink’ for free cysteine and can lead to metabolic vulnerabilities and toxicity in NRF2-activated tumours.

Two studies published in Nature Metabolism show that dysregulation of specific metabolic enzymes within the pancreas leads to increased oxidative stress, which promotes pancreatic neoplasia in the presence of oncogenic KRAS mutations.

By determining the organellar topology and proteome of fat-oxidizing and fat-synthesizing hepatocytes, Kang et al. show that perilipin 5-mediated mitochondria–lipid droplet contacts facilitate the expansion of lipid droplets in both populations and are impaired in early metabolic dysfunction-associated steatotic liver disease (MASLD).

In this issue of Nature Metabolism, Madi et al. show that triacylglycerol synthesis in T cells is essential for male, but not female, antitumour immune responses through sequestration of toxic lipids increased by androgen receptor signalling.

Dysfunction of specialized adipose endothelial cells has been implicated in the metabolic derangements observed in individuals with obesity and type 2 diabetes. In this issue of Nature Metabolism, AlZaim et al. provide a single-cell molecular atlas of the human subcutaneous adipose tissue and highlight the possible contributions of adipose endothelial cells to adipose tissue pathology.

Transient steatosis supports liver regeneration. In this study, Yao, Tian et al. show that lipid accumulation in a subset of monocyte-derived macrophages (MDMs) reprograms interleukin-6 secretion, via ceramide-dependent signalling, to promote hepatocyte proliferation.

A study published in Nature Metabolism shows that extracellular vesicles from a small group of hypothalamic α-tanycytes direct diurnal feeding behaviour to maintain body weight and glucose homeostasis.

KRAS mutations in colorectal cancers shape an immunosuppressive tumour microenvironment. In this issue of Nature Metabolism, Yang et al. report that TRIP6 phosphorylation-induced glycolysis in KRAS-mutant colorectal cancer impedes CD8⁺ T cell function by the intriguing extracellular lactylation of CD44.

By modelling protein abundance as continuous spatial gradients, the study by Weiss et al., published in this issue of Nature Metabolism, reframes liver zonation as a quantitative variable, enabling protein-level comparisons across individuals, species and disease states.

Dihydroorotate dehydrogenase (DHODH) is the only core de novo pyrimidine enzyme in the mitochondrial inner membrane, coupling nucleotide production to electron transport. Curtabbi et al. show that a cytosolic, fumarate-dependent DHODH orthologue can bypass this dependence, sustaining pyrimidine synthesis and supporting cell growth during respiration failure.

The glycerol-3-phosphate shuttle links redox balance to lipid synthesis, making the relief of reductive stress costly. Pan et al. rewire this circuit with a bifunctional enzyme that uncouples NAD⁺ regeneration from lipogenesis, restoring redox homeostasis under respiratory stress.

Calcium entry into mitochondria couples neuronal activity to energy supply, but whether boosting this drive can enhance brain function has remained unclear. Vishwanath et al. now demonstrate that tuning mitochondrial calcium extrusion enhances ATP production and improves cognitive performance in flies and mice, paving the way for a new paradigm of systems neurometabolism.

Taurine is essential for mitochondrial translation, yet its mitochondrial uptake mechanism remains unknown. Li, You, Chai et al. identify that SLC6A6, a plasma membrane taurine transporter, also localizes to mitochondria to import cytoplasmic taurine for mitochondrial transfer RNA modifications and metabolic reprogramming in cancer.

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.