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Yu et al. report a bioluminescence- and paper-based assay for the rapid quantification of NAD+ levels in biological samples, such as blood and tissues.
Persistent mitochondrial DNA stress is shown to upregulate nuclear DNA damage and repair responses via activation of the cGAS–STING pathway and a subset of interferon-stimulated genes.
The anti-diabetic drug metformin is shown to elevate plasma levels of the hormone GDF15. This increase in GDF15 is required for reductions in appetite and body mass, which are known to contribute to the beneficial metabolic effects of the drug.
Here the authors provide a regulatory framework for the cardiac mitochondrial ATP synthase, which is shown to be dependent on cellular activity; levels of Ca2+, ADP and NADH; and the potential of the inner mitochondrial membrane.
Increased mitochondrial DNA (mtDNA) replication frequency is shown to lead to defects in maintenance of the nuclear genome due to reallocation of nucleotides to mitochondria, challenging the proposed direct role of mtDNA mutations as drivers of cellular and organismal ageing in mammalian progerias.
The cellular effects of cold preservation in heart transplantation and how warm ischaemia leads to damage are unclear. Here the authors identify succinate accumulation as a major damaging metabolic change in warm ischaemia.
Cancer cells increase serine synthesis; however, exogenous serine is required for maximal proliferation. Here the authors show that the demand for oxidized NAD+ constrains serine synthesis, which is needed for purine production to support cell proliferation.
The role of skeletal muscle in non-shivering thermogenesis is not fully elucidated. Here the authors show that, in muscle, phospholipids can influence whole-body metabolic rate and counteract obesity by altering calcium signalling and inducing energy expenditure.
Asano et al. dissect the functional difference between the soluble and membrane-bound forms of RANKL. Membrane-bound RANKL is sufficient for most physiological RANKL functions, whereas soluble RANKL promotes bone metastases by stimulating tumour cell migration to bone, without affecting tumour cell growth or osteoclast differentiation.
m6A mRNA methylation regulates several cellular processes, including cancer progression and stem cell maintenance. Here, De Jesus and colleagues demonstrate that the m6A landscape segregates human type 2 diabetic islets from controls and that m6A is fundamental for human β-cell biology.
Caused by a compromised lymphatic system, lymphoedema leads to fluid retention and tissue swelling, and is treated primarily with physical therapy. Here the authors present a metabolic approach to reduce lymphoedema by providing the ketone body β-hydroxybutyrate or by feeding ketogenic diet, which increases lymphangiogenesis and reduces fluid retention in mice.
Glutamine is a major fuel for proliferating cells. Here the authors show that reduced dependence on exogenous glutamine is a generalizable feature of self-renewing pluripotent stem cells that can be exploited to select for mouse and human pluripotent stem cells with high self-renewal potential.
Here the authors report the results of a first-in-human trial with urolithin A in healthy elderly individuals, demonstrating that the compound is well tolerated and bioavailable after oral administration. They also provide clinical data indicating that urolithin A may improve mitochondrial and cellular health in human muscle.
Type 1 diabetes (T1D) involves immune-mediated destruction of pancreatic β cells. Here, the authors show that inducing β-cell replication before immune cell infiltration of the pancreas alters β-cell antigen expression and prevents T1D disease progression in female NOD mice in a regulatory-T-cell-dependent manner.
The transcription factor Klf15 controls various metabolic processes, including bile acid synthesis. Here the authors show that Klf15 acts as an upstream regulator of xenobiotic and endobiotic metabolism by controlling expression of a variety of phase I–III metabolic genes via direct and indirect mechanisms.
AMPK is a master regulator of cellular metabolism. Here the authors show that a constitutively active AMPK mutation protects mice fed a high-fat diet from obesity by increasing energy expenditure in subcutaneous white adipocytes, possibly as a result of the emergence of a hitherto-unknown type of adipocyte.
Olfactory food perception is known to extend lifespan in C. elegans. Here the authors demonstrate food-odour-dependent brain-to-gut communication that extends lifespan in worms. Food odour downregulates tir-1 mRNA in AWC neurons, in a manner dependent on the miRNA miR-71, which triggers downstream effects in the gut, due to neuropeptide secretion, that promote proteostasis and longevity.
Neurons and astrocytes cooperate metabolically but differ in key aspects of their metabolism, including the production of mitochondrial reactive oxygen species (ROS). Here, the authors show that mitochondrial ROS produced in astrocytes affect neuronal metabolism and mouse memory and behaviour.
Perineuronal nets (PNNs) are extracellular matrix structures that have been linked to neuronal plasticity in the cortex and hippocampus. Here, the authors report the existence of PNN-like structures in a key region regulating energy homoeostasis, the hypothalamic arcuate nucleus, and show that PNN formation in this area early in life is influenced by the hormone leptin.