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The Career Pathways series features the stories of Nature Metabolism authors and their self-professed journeys to publication as young investigators. This Collection brings together the Career Pathway pieces and the original research published in Nature Metabolism by the authors.
The transition from senior postdoc to early-stage investigator is a pivotal step in the careers of academic scientists. In this series, early-stage investigators reflect on their labs’ first publications and the journeys that led them there.
In this instalment of Career pathways, Kivanç Birsoy and Sarah Lessard recount their roads to scientific research and reflect on how each step in their training prepared them for life as a group leader.
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.
Creatine can be used for thermogenesis in adipocytes. Here Kazak et al. show that creatine uptake is required to sustain this thermogenic pathway. Knockdown of the creatine transporter, CrT, in adipocytes decreases thermogenesis and energy expenditure, whereas creatine supplementation increases energy expenditure in mice fed a high-fat diet.
Proinflammatory activation of liver macrophages and their secretion of proinflammatory cytokines have been linked to obesity. Here Morgantini et al. report a mechanism through which liver macrophages can impair liver metabolism and promote insulin resistance in obesity in the absence of an overt proinflammatory phenotype, through secretion of non-inflammatory factors such as IGFBP7.
Non-alcoholic steatohepatitis (NASH) is characterized by lipid accumulation within hepatocytes and fibrosis. Seitz et al. show that the GTPase protein Rab24 is increased in the livers of people who are obese or have NASH.
Macrophages engage in a sequence of dynamic functional changes during immune responses. Here the authors elucidate a two-stage remodelling of the tricarboxylic acid cycle during this process, which is driven by regulation of the pyruvate dehydrogenase and the oxoglutarate dehydrogenase complexes, and causes transient accumulation of immunoregulatory metabolites.
Pulsatile GABA secretion from human beta cells via the volume regulatory anion channel (VRAC) and subsequent uptake by the GABA-permissive taurine transporter (TauT) is shown to regulate total insulin secretion and pulsatility.
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.
The conventional view holds that hypoxia confers drug resistance. In contrast, here the authors use a multilayer ‘omics data approach to characterize the molecular features associated with tumour hypoxia and identify molecular alterations that correlate with both drug-resistant and drug-sensitive responses to approved drugs.
The muscular and organismal response to exercise training is reduced in animal models associated with chronic hyperglycaemia, thus suggesting that chronic hyperglycaemia inhibits aerobic adaptation to exercise.
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.
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.