Letters

Previously uncharacterized cysteine-derived conjugates, including with endogenous sugar metabolites, accumulate in cancer cells with constitutive NRF2 activation and account for some of the increased cystine uptake that cannot be explained by conventional cysteine metabolism.

Temporal profiling of central carbon metabolism during Kras^G12D-driven acinar-to-ductal metaplasia reveals that disruptions in NADPH-producing enzymes accelerate the formation of pancreatic precancerous lesions.

In the early stages of pancreatic ductal adenocarcinoma (PDAC) development, loss of ALDH1L2 expression elevates reactive oxygen species levels, driving accelerated acinar-to-ductal metaplasia. Decreased ALDH1L2 expression is accompanied by formate overflow, which can be used to monitor PDAC progression.

Leveraging pythons as an extreme model of feeding and fasting behaviour, this study uncovers para-tyramine-O-sulphate as a conserved postprandial metabolite that links nutrient intake to energy balance by activating hypothalamic neurons and suppressing food intake in pythons and mice.

Circadian clock in adipocytes maintains metabolic health by regulating mitochondrial complex I respiration.

Neri et al. develop elegant tools to understand how the sympathetic nervous system regulates intrascapular brown adipose tissue (iBAT) function. Using these tools, they find that sympathetic nerves targeting the iBAT parenchyma control local blood flow and heat production, while those innervating the iBAT vasculature regulate systemic glucose metabolism.

A comparison of the effects of different NAD⁺ boosters is lacking. This clinical study compares the efficacy of the NAD⁺ boosters NR, NMN and Nam in increasing circulating NAD⁺ levels and analyses their effects on gut microbial metabolism.

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.

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.

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.

Feng, Luo and colleagues show that the combination of glucose and fructose, as found in sugar-sweetened beverages, promotes colorectal cancer metastasis through a mechanism involving sorbitol dehydrogenase (SORD).

This study shows that the preferential use of gluconeogenic pathways in the liver depends on exercise load.

This study reveals neuronal targets of Lac-Phe in the hypothalamus that mediate its suppression of food intake.

In this study, Willenbockel et al. trace circulating itaconate in vivo to gain insight into its fate and systemic metabolism.

Kaluba, Rogers et al. show that in cancer cells that can metabolize ketones, they may reroute them to produce cytosolic acetyl-CoA and support tumour growth.

A series of fluorescent probes is designed that act as dual agonists on both GLP1 and GIP receptors, and are used to image receptor binding activities in tissues and animals.

Wang et al. report a workflow to perform quantitative mass spectrometry imaging and provide insight into spatial metabolic remodelling undergone in the mouse brain upon ischaemia.

Aspartoacylase expression in white adipose tissue regulates circulating levels of N-acetylaspartate, which in turn modulates plasma pyrimidine levels and regulates postprandial body temperature.

Andersson et al. show that intestinal stem cells enriched for old mitochondria are metabolically distinct and have enhanced ability to regenerate the epithelial niche.

A ketogenic diet and the ketone body β-hydroxybutyrate are shown to confer resistance to malaria in mice by inducing metabolic reprogramming in Plasmodium parasites, suggesting a dietary strategy for malaria prevention.