Articles in 2024

This month, Nature Metabolism turns five. For a young journal such as ours, this anniversary represents a milestone worth celebrating, and a welcome opportunity to look back.

Demicco, Liu et al. discuss how metabolic adaptations in cancer contribute to tumour progression. These adaptations entail high spatial and temporal metabolic heterogeneity, based on local adaptations in different regions of the tumour microenvironment, as well as metabolic evolution over time as the tumour progresses and metastasizes.

Dwibedi et al. carry out a randomized controlled trial to evaluate whether subgroups of patients with diabetes could receive the greatest metabolic benefit from novel anti-diabetic drugs.

Miotto et al. show that in mice, liver-derived extracellular vesicles act on skeletal muscle and the pancreas and increase glucose effectiveness and insulin secretion, thereby modulating glycaemic control.

Genotype at the LCT locus determines lactase expression and very notably varies across populations. Milk intake variably influences the aetiology of the risk of type 2 diabetes depending on ancestry. In this issue of Nature Metabolism, Luo et al. describe how increased milk intake modifies both gut bacterial abundances and circulating metabolites in favour of decreasing the risk of type 2 diabetes in individuals who are lactase-deficient.

Higher milk intake is associated with lower type 2 diabetes risk in lactase non-persistent individuals, partly through gut microbiome and blood metabolites.

Electron transfer flavoprotein dehydrogenase (ETFDH), respiratory chain complex III and the coenzyme Q10 synthesis regulator COQ2 interact as a protein complex that is disrupted in ETFDH deficiency, with potential implications for disease therapy.

During ageing, S-adenosylmethionine (SAM) is depleted from muscle stem cells (MuSCs) because of increased synthesis of the polyamine spermidine, leading to loss of heterochromatin and dysfunction of MuSCs. SAM restoration rescues the mouse MuSC defects.

Electron-transfer flavoprotein dehydrogenase (ETFDH) is shown to associate with mitochondrial complex III (CIII) physically and functionally, thereby promoting electron channelling to increase CIII efficiency.

Following one’s passion and curiosity are major drivers for a successful career in science, and finding the right mentors and collaborators is essential in this journey. In the thirteenth part of our Career pathways series, Alexis Jourdain and Feilong Wang share their experience.

Yu et al. show that inhibition of p21-activated kinase 4 (PAK4) ameliorates insulin resistance and enhances lipolysis by reducing phosphorylation of fatty acid-binding protein 4 (FABP4) and hormone-sensitive lipase (HSL). In parallel, PAK4 inhibition increases energy expenditure.

Bone resorption by osteoclasts requires tight control, as overactivation reduces bone mass and strength. Stegen et al. demonstrate that α-ketoglutarate produced during serine synthesis promotes osteoclast development via metabolic–epigenetic coupling and could be a therapeutic target.

Stegen et al. show that serine metabolism is transiently upregulated during osteoclastogenesis, and it drives osteoclast differentiation via epigenetic regulation of NFATc1 expression.

Using several orthogonal loss-of-function approaches, Huang et al. provide a detailed assessment of the quantitative contribution of δ cell paracrine signalling to the glycaemic set point in mice.

Zhang et al. show that in mice, an adipocyte population with high expression of the transcription factor JunB in the brown adipose tissue shows reduced thermogenic capacity. Depletion of JunB increases the fraction of adipocytes with high thermogenic capacity and ameliorates diet-induced insulin resistance.

Systematic evaluation of glucose control, body mass index, blood pressure, insulin secretion and insulin resistance is leveraged to identify patients who are likely to receive the greatest metabolic benefit from common antidiabetic drugs.

Murine blastocysts and embryonic stem cells mimicking the pre-implantation epiblast import extracellular protein through macropinocytosis and engage a robust lysosomal digestive programme to meet their nutrient demands. We found that as development proceeds, post-implantation epiblast-like cells downregulate protein digestion, increase expression of amino acid transporters and become dependent on soluble amino acids.

Todorova et al. characterize the strategies through which embryos secure amino acid supply during the early phases of development. Their findings show that, in the preimplantation phase, embryos uptake whole proteins through macropinocytosis and, over time, they shift towards soluble amino acid uptake. This strategy may contribute to protecting embryos from nutrient fluctuations.

In nature, organisms constantly face a variety of stresses in the environment. An organism’s ability to resolve a stressful state is crucial in maintaining homeostasis. In this issue of Nature Metabolism, Wei et al. report that redox-dependent caspase cleavage of fatty acid synthase triggers a global cue for stress resolution in Caenorhabditis elegans.