Articles

Yao and Gong et al. identify WD40 repeat-containing protein 6 (WDR6) to be upregulated in the liver of insulin-resistant mice. WDR6 contributes to promoting hepatic de novo lipogenesis during insulin resistance by upregulation of fatty acid synthase, and the authors identify a small molecule to inhibit this effect of WDR6 and reduce hepatic steatosis.

The authors explore the molecular signature of skeletal muscle adaptations to an acute bout of exercise in mice, providing a valuable resource that includes transcriptomic, epigenetic, proteomic and phosphoproteomic changes in muscle plasticity.

Longitudinal deep lipidome profiling reveals >800 lipid species, many of which are associated with health-to-disease transitions in diabetes, ageing and inflammation.

This study reports the mouse islet atlas, a curated resource integrating scRNA-seq data of over 300,000 cells from nine datasets, covering pancreas development, homeostasis and disease states.

TMEM164 is an early-response intrinsic factor that inhibits the induction of neurotoxic reactive astrocytes, and whose astrocyte-specific overexpression alleviates the symptoms of neurodegenerative diseases in mice.

In this study, Wang et al. show that the glycolytic metabolite phosphoenolpyruvate, produced by enolase 2, contributes to colorectal cancer malignancy and resistance to antiangiogenic therapy by inhibiting endogenous histone deacetylase 1 and favouring β-catenin signalling.

Dutta et al. show that impaired mitochondrial fatty acid synthesis (mtFAS) leads to neurodegeneration, increased ceramide levels and disturbed iron metabolism in flies and in fibroblasts from individuals with a mutation in an mtFAS enzyme.

Here Mukherjee et al. characterize the bidirectional communication between adipose tissue and ovarian cancer cells and show that adipocytes instruct cancer cells to divert glycolytic glycerol-3-phosphate towards lipid synthesis, thus promoting metastasis.

The authors identify a role for GABRA5 neurons in the lateral hypothalamus for energy balance regulation. Inhibiting these neurons increases weight gain and lipid accumulation through a process dependent on astrocytic GABA release.

In this study, Okreglak et al. identify dynamic regulation of pH in the lysosome-like vacuole of growing S. cerevisiae cells and link pH dynamics in this subcellular compartment to amino acid release into the cytoplasm to meet metabolic demands during cell cycle progression.

Minogue et al. show that glutarate, a metabolite derived from tryptophan catabolism, has the ability to shape anti-tumour T cell responses by modulating pyruvate handling and alpha-ketoglutarate-dependent dioxygenases.

Hanssen et al. demonstrate that associative learning is reduced when metabolic sensing is impaired in obesity and can be restored by liraglutide.

The authors uncover a brain-to-stomach signalling axis that communicates gastric dysfunction associated with stress.

In this study, the anti-anginal drug ranolazine is found to sensitize BRAF inhibitor-resistant melanoma to targeted therapy and immunotherapy by rewiring fatty acid oxidation and the methionine salvage pathway.

In this study, Wang, Xu et al. investigate the interaction of neutrophils and T cells in lymphoid tissues away from the tumour area, and how metabolic competition between these immune cell populations impairs anti-tumour immunity in the context of breast cancer.

Gnanaprakasam et al. study the amino acid requirements during different phases of T cell activation and show how asparagine restriction imparts opposing effects during early and late phases of T cell maturation through an NRF2-dependent mechanism.

Dietary methionine restriction has been reported to protect from cancer. Ji et al. describe a cancer-promoting effect of methionine restriction mediated by gut microbiota-induced sulfur deficiency and suppression of antitumour immunity.

Suchacki et al. show that serotonin suppresses human brown adipose tissue (BAT) activation, and that inhibition of the serotonin transporter (SERT) potentiates the suppressive action of extracellular serotonin on BAT by preventing serotonin uptake.

Huang et al. develop an interface to allow electrode-mediated stimulation of gene expression in human cells, utilizing direct current-generated reactive oxygen species to stimulate transgene expression downstream of the KEAP1–NRF2 biosensor. In a type 1 diabetic mouse model, this interface is demonstrated to ameliorate hyperglycemia by stimulating insulin expression.

Variants in the FTO gene locus are known to be associated with obesity, including rs1421085 T>C variant, and now it is shown in mouse knock-in models that this C-allele increases expression of the Fto gene in brown adipocytes and enhances brown adipose tissue thermogenesis and obesity resistance.