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Fasolino et al. provide insights into ductal cell roles and type 1 diabetes pathogenesis using a pancreatic islet single-cell atlas generated by the Human Pancreas Analysis Program.
Zhong, Wan and Cai et al. show that deficiency of the microsomal prostaglandin E synthase-2 (mPGES-2) in pancreatic β-cells improves glucose metabolism and insulin secretion in mice by inhibiting β-cell senescence and dysfunction during diabetes.
In the Drosophila starved brain, memory formation undergoes adaptive plasticity. Silva et al. show that neurons in the olfactory memory centre of the starved fly are fuelled by glial-derived ketone bodies in order to sustain memory formation.
The GDF15–GFRAL axis is key for regulating energy homeostasis and body weight. Membrane-bound matrix metalloproteinase 14 is shown to negatively regulate GFRAL, whereas its downregulation protects against diet-induced obesity through increased GDF15 signaling.
Maqdasy, Lecoutre et al. show that increased an phosphocreatine/creatine ratio in white adipocytes drives changes in AMP-activated protein kinase activity and promotes white adipocyte inflammation during obesity.
Hirano et al. show that expression of the MYC family member Mycl in adult pancreatic islets can increase proliferation and expand the functional β-cell population, thereby improving glucose control.
Employing a candidate gene approach, Mancina et al. identify a genetic variant of the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene that reduces susceptibility to fatty liver disease. Functional studies in vitro and in vivo demonstrate that targeting PSD3 protects against fatty liver disease.
Endothelial cell metabolism is shown to regulate blood vessel maturation by controlling vascular matrix composition and the recruitment of vascular mural cells.
Ma et al. show that acetylation of PRDM16 via acetyl-CoA, derived from branched-chain keto acids, impairs PRDM16–PPAR interaction, thus linking the BCAA–BCKA axis to the regulation of white adipose tissue browning.
Kahraman et al. show that transfer of mutant CEL protein from pancreatic acinar cells to β cells causes β-cell dysfunction, providing insight into the mechanism underlying MODY8.
While glucose homeostasis in the circulation is tightly controlled by insulin and other hormones, dedicated hormonal regulators do not exist for most other circulating metabolites. Using perturbative metabolite infusions with isotope labelling in mice, Li et al. show that homeostasis of many circulating metabolites is considerably regulated through mass action-driven oxidation.
Inhibiting the cytosolic enzyme histone deacetylase 6 in the periphery is sufficient to improve leptin sensitivity and metabolic outcomes in diet-induced obese mice.
Dong and Sun et al. show that adipogenesis regulatory cells in murine white adipose tissue inhibit adipogenesis through RSPO2, which regulates maturation of early progenitor cells via Lgr4.
Using a combination of metabolomics and bacterial and host genetics, Pruss et al. show that upregulated oxidative ornithine metabolism in Clostridioidesdifficile promotes its persistence within the gastrointestinal tract under non-inflammatory conditions.
Zhong et al. show that the protein GP73 stimulates hepatic glucose production and is induced in response to infection with SARS-CoV-2 in vitro and in vivo, thus proposing a molecular mechanism underlying hyperglycemia associated with COVID-19.