Articles in 2024

By increasing NAD⁺ consumption in various organelles, mitochondria are revealed to act as buffers that help maintain subcellular NAD⁺ levels. At the same time, cells are found to be particularly sensitive to a decline in NAD⁺ levels originating from mitochondria themselves.

Combining rabies-based connectomics with single-nucleus transcriptomics, the authors identify a neural circuit through which GLP-1 receptor agonists suppress appetite in mice.

Nam et al. show that limited glucose availability similar to the tumour microenvironment confers resistance against chemotherapeutic drugs that target DNA synthesis.

Castells-Nobau et al. provide insight into how bacteriophages in the gut microbiome contribute to regulating food addiction by modulating tryptophan and tyrosine metabolism in the host.

The insulin inhibitory receptor (inceptor) is found to bind to insulin and to regulate insulin stores by directing proinsulin and insulin towards lysosomal degradation.

The authors highlight the role of acyl coenzyme A binding protein (encoded by DBI) in Cushing’s syndrome by using six different inhibition methods and mapping the physiological effects.

The NAD⁺ synthesis enzyme NAMPT is shown to possess additional enzymatic activity as a phosphoribosylase, which restricts the virion incorporation of viral proteins and underpins its antiviral effect

The authors show how genetic variants of the human circadian clock gene PER3 are related to winter depression. In mice, under shorter light exposure, such variants enhance glucocorticoid signalling, inhibiting serotonin production and leading to depression-like behaviours.

Interleukin-10 promotes the formation of microcirculatory defects in the brain associated with cognitive impairment in a mouse model of type 1 diabetes.

Branched-chain α-ketoacids are shown to aerobically activate HIF1α signalling, which induces a phenotypic switch in vascular smooth muscle cells that is potentially relevant in the context of pulmonary artery hypertension.

Malik, Guo et al. show that Ntrk2/Trkb-mediated neurotrophic signalling regulates dopamine levels by controlling glutathione–ascorbate metabolism, thus impacting striatal dopaminergic circuits and motor function

The mevalonate pathway intermediate farnesyl pyrophosphate is shown to regulate the survival of migratory dendritic cells by affecting their mitochondrial metabolism, thereby contributing to the pathogenesis of systemic lupus erythematosus.

Korobkina et al. show that ACLY in brown fat prevents metabolic overload in the tricarboxylic acid cycle, thus ensuring adequate thermogenesis by avoiding cellular stress.

Genetic and pharmacological inhibition of the overproduction of oxalate in the liver alleviates metabolic dysfunction-associated steatohepatitis in male mice.

The authors systematically study biological influences on the human plasma proteome in a large cohort, thereby revealing causal associations between plasma proteins and modifiable risk factors for protein–disease associations.

LXRα is highly expressed in hepatocytes, where it regulates cholesterol abundance and stimulates lipogenesis. The authors provide evidence in humans and mice that impaired LXRα signalling is hepatotoxic, despite its potent lipogenic actions.

Oral administration of the anti-diabetic drug acarbose is shown to enhance the efficacy of cancer anti-PD-1 immunotherapy in female mice by modulating the composition and metabolism of the gut microbiota.

Exercise training decreases pancreatic islet senescence through glucagon and AMPK signalling in mouse and human islets, which could have implications for T2DM therapeutics.

Wang et al. show how glucose sensing via O-GlcNAcylation drives the assembly of a glycolytic metabolon on the mitochondrial surface to couple metabolic efficiency with neuronal activity.

Adults with overweight or obesity who exercise regularly for at least 2 years exhibit distinct structural and proteomic characteristics in abdominal subcutaneous adipose tissue that may contribute to better cardiometabolic health outcomes.