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In young women, brain insulin action enhances peripheral insulin sensitivity, but only during the follicular phase of the menstrual cycle. This effect is absent in the luteal phase, possibly due to hypothalamic insulin resistance.
Gao et al. perform functional profiling of 60 genetic variants of glucagon-like peptide 1 receptor (GLP1R) in vitro, and link variants with impaired GLP1R cell surface expression or cAMP activation to defective insulin secretion in vitro and to impaired glucose homeostasis and adiposity in the UK Biobank.
Perszyk et al. identify the neural basis for odour-imagery ability and show that it indirectly predicts weight-gain susceptibility through a mechanism that is dependent on food-cue reactivity.
In this study, Vande Voorde et al. investigate the potential of untargeted metabolomics as a stratification tool for colorectal cancer (CRC). They present a comprehensive pipeline to uncover metabolic vulnerabilities in CRC based on its genetic origin. With this approach, they show perturbations in methionine metabolism linked to APC deficiency, and identify adenosylhomocysteinase as an actionable therapeutic target.
In this study, Morant-Ferrando, Jiménez-Blasco et al. show that fatty acid oxidation in astrocytes is necessary to maintain a specific configuration of the electron transport chain, which enables controlled production of reactive oxygen species that fine-tune neuron–glia metabolic coupling and support cognitive function.
Alterations in the gut microbiome, as a result of treatment with the anti-diabetic drug acarbose or with antibiotics, are shown to extend healthspan and lifespan in a mouse model of Leigh syndrome.
This study shows that the insulinotropic actions of the dual GIPR and GLP-1R agonist, tirzepatide, depend on GIPR, and that tirzepatide has weaker activity at the mouse GIPR than murine GIP.
In this study, Skinner, Blanco-Fernández et al. show that uridine can be salvaged through the non-oxidative branch of the pentose phosphate pathway to feed glycolysis in conditions of glucose scarcity.
The authors use a non-invasive sampling device to collect intestinal samples in 15 healthy male and female participants and analyse them through mass spectrometry and 16S rRNA sequencing. They identify thousands of biomolecules throughout the intestinal tract, many of which remain unknown and highlight differences between intestinal and stool metabolomes.
Using a database of doubly labelled water energy expenditure measurements spanning more than 30 years, Speakman and colleagues show that total energy expenditure in humans has declined over time, while adjusted physical activity energy expenditure has increased over time.
Govaere et al. integrate circulating protein data from more than 300 patients with non-alcoholic fatty liver disease (NAFLD) with transcriptomics and develop a non-invasive diagnostics tool to identify patients with at-risk NAFLD based on body mass index, type 2 diabetes status and four circulating proteins.
Primary cilia are shown to adjust length in response to cellular nutrient availability, with a special role for glutamine-mediated anaplerosis via the enzyme ASNS, which was found to be located at the base of cilia. Consistently, cells lacking cilia show an altered response to glutamine during metabolic stress.
A new transplantation site in the abdomen, the subanterior rectus sheath, is shown to allow for functional maturation of stem-cell-derived islet cells and improved glycemic control in a proof-of-principle study involving four nonhuman primates.
Jing et al. show that COVID-19 infection causes white adipose tissue (AT) browning in mice and hamsters, which is mediated by VEGF action in the AT. VEGF blockade can ameliorate browning phenotype and COVID-19-induced weight loss, potentially providing a strategy to treat infection-induced AT atrophy.
Itaconate is a metabolite with immune-modulatory effects in myeloid cells. In this study, Zhao, Teng et al. report an additional role for itaconate in CD8+ T cells, with implications for immune surveillance and anti-tumour immunity.
Rahbani et al. show that the α1-adrenergic receptor potentiates thermogenesis in thermogenic adipocytes, acting via Gαq signalling, creatine kinase B and tissue-non-specific alkaline phosphatase.
Wolfson et al. show that microbial hydrogen sulfide contributes to the nonenzymatic reduction of azo xenobiotics, which include food dyes and drugs. This modulates sulfur homeostasis, xenobiotic metabolism and the chemical landscape of the gut.
Understanding dynamic metabolic changes in complex biological samples often overlooks heterogeneity in cell composition. Wang et al. combine mass spectrometry imaging, isotope tracing, and multiplexed immunofluorescence microscopy to study metabolic dynamics in the kidney upon ischemia–reperfusion.
A single transfer of blood from old male mice is shown to induce cellular and tissue senescence in young animals, unless old mice are treated with senolytic drugs before blood exchange.
The key regulator of lysosomal biogenesis, Tfeb, is shown to directly induce Irg1 transcription and mitochondrial itaconate production to restrain bacterial growth in macrophages.