Reviews & Analysis

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  • Evers et al. explore the interconnection between cellular mechanics and metabolism, emerging paradigms and the role of this interaction in cancer, cardiovascular disease and fibrosis.

    • Tom M. J. Evers
    • Liam J. Holt
    • Alireza Mashaghi
    Review Article
  • Colchicine is an anti-inflammatory agent that suppresses myeloid cell activation and is commonly used to treat gout. In this issue of Nature Metabolism, Weng et al. demonstrate that colchicine exerts its anti-inflammatory effects in mice via the induction of the hormone GDF-15 in the liver.

    • Samuel M. Lockhart
    • Stephen O’Rahilly
    News & Views
  • Brown adipose tissue acquires increased thermogenic capacity with prolonged cold exposure through de novo recruitment of brown adipocytes. Studies by Shamsi et al. and Angueira et al. identify novel cellular origins of cold-induced brown adipocytes and further elucidate the molecular mechanism regulating the expansion of brown adipose tissue.

    • Alana Deutsch
    • Kosaku Shinoda
    News & Views
  • Redox cofactors are essential for the metabolic reactions that support cell proliferation. NADPH is important both to combat oxidative stress and to facilitate reductive reactions in biosynthesis. In this issue, Tran et al. find that the enzyme that produces mitochondrial NADPH is critical in enabling proline synthesis to support cell proliferation when environmental proline is limited.

    • Frances F. Diehl
    • Matthew G. Vander Heiden
    News & Views
  • Learning to balance work, family, optimism and setbacks is a process for all early-career investigators. Stephanie Correa and Leng Han share their stories in this instalment of Career pathways.

    • Stephanie Correa
    • Leng Han
    Viewpoint
  • Obesity is associated with mitochondrial dysfunction and chronic metabolic derailment. Cho et al. report that elevated adipose expression of the Hippo kinases STK3 and STK4 (STK3/4) in obesity and type 2 diabetes decreases the mass and oxidative capacity of adipocyte mitochondria. Genetic or pharmacological inhibition of STK3/4 restores mitochondrial mass and function in adipocytes and improves glucose homeostasis in mice with diet-induced obesity. These findings support STK3/4 as new targets for obesity-related diseases.

    • Kathrin Maedler
    • Amin Ardestani
    News & Views
  • It is self-evident that consuming alcohol affects brain function and behaviour. What is not clear, however, is how alcohol does so. A new study shows that impairments in balance and motor coordination evoked by low-dose alcohol are mediated not by ethanol itself but by one of its metabolites, which is produced locally by astrocytes in the brain rather than in the liver.

    • Riccardo Melani
    • Nicolas X. Tritsch
    News & Views
  • Flippo and Potthoff provide a concise overview of the major physiological and pharmacological effects of FGF21 in nutrient and energy homeostasis.

    • Kyle H. Flippo
    • Matthew J. Potthoff
    Metabolic Messengers
  • Nutrient availability dictates cell differentiation and transition through the Dictyostelium discoideum life cycle. Kelly et al. reveal that the increase in reactive oxygen species associated with nutrient limitation coincides with a sequestration of available cysteine in glutathione, thus limiting sulfur-dependent mitochondrial respiration and promoting aggregation into the differentiated spore form.

    • Nathan P. Ward
    • Gina M. DeNicola
    News & Views
  • Deciphering the origins of the various cells in atherosclerotic plaques, the regulation of their fates and their functions is an essential step towards developing strategies to limit or even reverse disease progression to myocardial infarction. In this issue, Newman et al. advance our understanding of the roles of non-vascular smooth muscle cells in the formation and maintenance of the fibrous cap, a structure in human atherosclerotic plaques that protects them against rupture—the proximal event typically underlying myocardial infarctions.

    • Ashish Misra
    • Edward A. Fisher
    News & Views
  • Exhaustion of pancreatic beta cells in the face of prolonged insulin resistance results in the development of type II diabetes. Ansarullah et al. now describe an inhibitor of beta-cell insulin signalling that, on removal, increases beta-cell mass and improves beta-cell function, with potential as a new way to address beta-cell failure.

    • James G. Burchfield
    • David E. James
    News & Views
  • Cancer cells undergo metabolic rewiring to support unrestrained proliferation, but dependence on oncogenesis-supportive metabolites could be leveraged therapeutically. Geeraerts et al. explore the centrality of serine and glycine metabolism to cancer survival, and how targeting the de novo serine and glycine synthesis pathways can complement current therapies.

    • Shauni L. Geeraerts
    • Elien Heylen
    • Kim R. Kampen
    Review Article
  • Mitochondrial diseases are caused by genetic variants in either nuclear or mitochondrial DNA, and they have no known treatments. A new study by Perry et al. in this issue of Nature Metabolism used a drug screen to identify the widely available antibiotic doxycycline, an inhibitor of mitochondrial translation, as a potential pharmacological treatment for mitochondrial diseases.

    • Divakar S. Mithal
    • Navdeep S. Chandel
    News & Views
  • A creatine futile cycle has been shown to contribute to energy expenditure in beige adipocytes in preclinical mouse models of obesity. In this issue of Nature Metabolism, Connell and colleagues show that creatine supplementation in healthy young female vegetarians unfortunately affects neither human brown adipocyte activity nor cold-induced energy expenditure.

    • Salvatore Modica
    • Christian Wolfrum
    News & Views
  • Liver function depends on the temporal and zonal distribution of complementary metabolic tasks in hepatocytes. A new study by Droin et al. highlights how chronobiology and liver zonation orchestrate liver metabolism at single-cell resolution.

    • Stefano Annunziato
    • Jan S. Tchorz
    News & Views
  • Gribble and Reimann provide a concise overview of the core physiology of GLP-1 secretion and action, and the roles of GLP-1 in human health, disease and therapy.

    • Fiona M. Gribble
    • Frank Reimann
    Metabolic Messengers
  • In this instalment of Career pathways, Jing Fan and Edward A. Phelps reflect on fostering their newly formed research programs in the face of challenges both familiar and new.

    • Jing Fan
    • Edward A. Phelps
    Viewpoint