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Aregger et al. provide an approach to study genetic interactions in mammalian cells and describe genetic interaction maps that characterize genes involved in lipid metabolism. They identify the role of C12orf49, a previously uncharacterized gene, in regulating lipid uptake in human cells.
Bayraktar et al. construct a metabolic coessentiality network to cluster metabolic genes into networks from perturbation datasets derived from 558 cancer cell lines. They identify C12orf49 as an essential component of SREBP processing and cholesterol sensing in mammalian cells.
An automated decision support system is reported that provides weekly insulin dosage recommendations to users with T1D and that, when analysing previously collected patient data, exhibits high agreement with recommendations from physicians.
Itaconate production is a hallmark of inflammatory activated macrophages. Swain et al. compare the biological effects of itaconate and its common derivatives, identifying a new regulatory mode of inhibiting IL-1β secretion and enhancing IFN-β signalling.
Thermogenic adipose tissue has been suggested as a potential target to treat metabolic diseases. Here, Tran et al. show that a long noncoding RNA, LINC00473, is induced during activation of thermogenic adipocytes and regulates energy metabolism through interorganelle communication.
Currently, there is no approved treatment for NAFLD and NASH. Here, Boland et al. show that the GLP-1R and GCGR dual-agonist cotadutide reduces hepatic steatosis, inflammation and fibrosis via GCGR agonism, and glucose homeostasis and weight gain by activating GLP-1 signalling.
Tharyan et al. identify NFYB-1 as a regulator of mitochondrial function that represses lysosomal prosaposin. The NFYB-1–prosaposin signalling axis coordinates lysosomal-to-mitochondria signalling via cardiolipin to enhance cellular mitochondrial function and longevity in C. elegans.
Morphological changes in kidney glomerular ultrastructure and altered compression of the glomerular basement membrane are shown to correlate with albuminuria.
β-cell dysfunction in diabetes is caused by glucose and inflammation toxicity. Here, Fu et al. show that β-cell glucose metabolism can be protective though pyruvate carboxylase–mediated shunting of arginine to ureagenesis and away from toxic nitric oxide production, thus suppressing inflammation.
Wei et al. show that the chromatin regulator MRG15 interacts with the nuclear receptor LRH-1 and is rhythmically recruited to lipid- and cholesterol-biosynthetic genes. In a nutrient-rich state, MRG15 alters histone acetylation status to activate gene transcription and lipid synthesis, whereas in a nutrient-scarce state, MRG15 genomic recruitment and lipid synthesis are reduced.
Metabolic compensation equips tumours with the plasticity to circumvent individual nutrient pathway perturbation. Méndez-Lucas et al. demonstrate the power of synergistic targeting of multiple metabolic pathways to stymie liver tumourigenesis.
Yang et al. report that adenosine kinase possesses NRH kinase activity that enables it to convert NRH into NAD+, thus revealing a new salvage pathway for NAD+ biosynthesis operating in mammalian cells.
Tumour recurrence is a common cause of death for patients with cancer. Here Fox et al. show how the antioxidant transcription factor Nrf2 is activated in dormant residual tumour cells and promotes their proliferation and tumour growth by inducing a metabolic reprogramming aimed to maintain redox homeostasis and nucleotide synthesis.
The ventromedial nucleus of the hypothalamus is known to maintain energy homeostasis by controlling locomotor activity and thermogenesis. Here van Veen and Kammel et al. identified heterogeneous neuronal populations with sexually dimorphic gene expression and functions by using single-cell RNA analysis.
Brett et al. demonstrate that voluntary exercise improves quiescent muscle stem cell (MuSC) function and regenerative capacity in old but not young mice through exercise-induced upregulation of Cyclin D1 and repression of TGF-β activity in quiescent MuSCs.
The immune system is known to play an important role in regenerative processes. Here, Baht and colleagues identify Metrnl, a myokine/cytokine expressed in macrophages, as mediator of muscle regeneration. Metrnl promotes macrophage IGF-1 production that, in turn, activates satellite cells.
Li and colleagues show how cMyc promotes tumourigenesis by promoting succinate dehydrogenase complex subunit A acetylation by activating SKP2-mediated degradation of SIRT3. This leads to succinate accumulation and consequent tumour-specific gene expression.
Anhê et al. demonstrate that bacterial signatures of plasma, liver and three distinct adipose tissue depots can distinguish between type 2 diabetes and normoglycaemia in people with obesity.