Articles in 2021

Increasing compositional uniqueness of the gut microbiome, and corresponding changes in microbial metabolites in the blood, are identified as a signature of healthy ageing in humans.

GLP-1 is an incretin hormone and neuromodulator produced by gut enterocytes and CNS neurons. Brierley et al. find that GLP-1 from peripheral and central sources acts independently through distinct gut–brain circuits to suppress eating.

Exhaustion of pancreatic beta cells in the face of prolonged insulin resistance results in the development of type II diabetes. Ansarullah et al. now describe an inhibitor of beta-cell insulin signalling that, on removal, increases beta-cell mass and improves beta-cell function, with potential as a new way to address beta-cell failure.

SARS-CoV-2 is shown to infect and replicate in human pancreatic tissue, including in β-cells, which is associated with morphological, transcriptomic and functional changes.

Cancer cells undergo metabolic rewiring to support unrestrained proliferation, but dependence on oncogenesis-supportive metabolites could be leveraged therapeutically. Geeraerts et al. explore the centrality of serine and glycine metabolism to cancer survival, and how targeting the de novo serine and glycine synthesis pathways can complement current therapies.

On the second anniversary of Nature Metabolism, we reflect on some of the developments at the journal against the backdrop of this extraordinary year.

Mitochondrial diseases are caused by genetic variants in either nuclear or mitochondrial DNA, and they have no known treatments. A new study by Perry et al. in this issue of Nature Metabolism used a drug screen to identify the widely available antibiotic doxycycline, an inhibitor of mitochondrial translation, as a potential pharmacological treatment for mitochondrial diseases.

A creatine futile cycle has been shown to contribute to energy expenditure in beige adipocytes in preclinical mouse models of obesity. In this issue of Nature Metabolism, Connell and colleagues show that creatine supplementation in healthy young female vegetarians unfortunately affects neither human brown adipocyte activity nor cold-induced energy expenditure.

Xu et al. show that liver ATF3 expression is inhibited by hydrocortisone, thus promoting the development of atherosclerosis through effects on HDL cholesterol and bile acid metabolism.

In an unbiased screen, Perry et al. find that tetracycline antibiotics improve resilience of cultured cells carrying disease-associated mitochondrial DNA mutations. Doxycycline is shown to increases survival, and reduce symptoms, in a mouse model of Leigh syndrome.

Creatine availability is known to affect creatine-driven thermogenesis in mice. Here Connell et al. report data from a clinical trial in which daily creatine supplementation, perhaps surprisingly, did not alter thermogenesis in adults with otherwise low dietary creatine intake.

Li et al. report a non-metabolic role of NADPH as an inhibitor of HDAC3, thus linking NADPH levels with the epigenetic state of a cell.

Liver function depends on the temporal and zonal distribution of complementary metabolic tasks in hepatocytes. A new study by Droin et al. highlights how chronobiology and liver zonation orchestrate liver metabolism at single-cell resolution.

The prevalence of COVID-19-associated diabetes is not the result of a single event but of a combination of disease susceptibility associated with chronic illness and COVID-19-specific mechanisms affecting metabolism. Whether a separate entity of post-COVID-19 diabetes, possibly associated with lasting β-cell damage, also exists is not yet clear.

Gribble and Reimann provide a concise overview of the core physiology of GLP-1 secretion and action, and the roles of GLP-1 in human health, disease and therapy.

Previously, liver zonation was analysed statically, and liver chronobiology was analysed at the tissue level. Using single-cell RNA-seq and single-molecule FISH, Droin et al. study the interplay between liver gene regulation in space and time at the sub-lobular scale.

In this instalment of Career pathways, Jing Fan and Edward A. Phelps reflect on fostering their newly formed research programs in the face of challenges both familiar and new.

The tumour microenvironment (TME) is a unique cellular and metabolic landscape. Elia and Haigis describe how metabolism influences, and is affected by, the complexity of cellular interactions within the TME and highlight opportunities for therapeutic intervention.