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In a screen of peripheral blood cells from fasted or fed individuals, Han et al. identify FOXO4 and its target FKBP5 as fasting-induced modulators of CD4+ T helper cell responsiveness.
Zhao et al. use genetic lineage tracing to demonstrate that pancreatic endocrine and exocrine progenitor cells do not generate new beta cells, thus arguing against beta-cell neogenesis in the adult mouse pancreas.
Insulin stimulates TUG cleavage to translocate GLUT4 and enhance glucose uptake. Here Bogan and colleagues show that the TUG cleavage product regulates thermogenic gene transcription, thereby coupling glucose uptake to organismal energy expenditure.
Newman et al. explore the origins of myofibroblasts in atherosclerotic fibrous caps, finding that while composed of cells from multiple origins, smooth muscle cells predominate and are required for long-term plaque stability.
Choi et al. highlight the centrality of glycolysis in squamous cell carcinoma, revealing the glycolysis-dampening tumour suppressor role of Sirt6, and identifying a subset of highly glycolytic tumour-propagating cells with elevated antioxidant capacity.
Not all individuals with obesity develop cardiometabolic complications. Huang et al. use genome-wide meta-analysis to identify genetic loci associated with lower cardiometabolic risk despite increased adiposity.
Bosch-Queralt et al. find that diet-induced obesity impairs restoration of CNS demyelination through increased TGFβ-mediated suppression of cholesterol efflux.
The cap-binding protein eIF4E is a master regulator of mRNA translation. Conn et al. identify a specific subset of mRNAs governing lipid metabolism and storage that require eIF4E for translation in the liver during obesity.
Ketogenesis is critical for survival during the neonatal and perinatal periods. Arima et al. determine that hepatic ketogenesis prevents hyperacetylation of mitochondrial proteins and disruption of mitochondrial energetics.
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.
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.
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.
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.
The localization of long non-coding RNAs plays a vital role in regulating cellular processes. In addition to compiling a database of organelle-associated lncRNAs, Sang et al. identify a role for the lncRNA GAS5 in regulating tricarboxylic acid cycle enzymes during nutrient stress.