News & Comment

  • Editorial |

    As the world came to a standstill in the spring of 2020, so did the work on our Focus issue on exercise metabolism and health, which was originally scheduled for publication to coincide with the 2020 Summer Olympic Games.

  • Comment |

    Individual differences in physical performance in the sedentary state and in response to exercise training have been observed in rodent and human studies. The genomic variants underlying these genetic components are unknown. Nonetheless, without a rich genetic endowment, world-class athletic performance is out of reach.

    • Mark A. Sarzynski
    •  & Claude Bouchard
  • News & Views |

    Aberrant upregulation of de novo lipogenesis is linked to non-alcoholic fatty liver disease and some cancers. A new study by Kelly et al. finds that inhibiting this pathway by blocking the activity of acetyl-CoA carboxylase has unexpected effects on the formation of platelets from megakaryocytes within the bone marrow of primates but not rodents, thus suggesting clinical implications for de novo lipogenesis inhibitors as a new class of therapeutics.

    • Ishac Nazy
    • , Donald M. Arnold
    •  & Gregory R. Steinberg
  • News & Views |

    Islet of Langerhans transplantation as a cell therapy for type 1 diabetes faces obstacles that have prevented full and lasting engraftment in the liver, the currently preferred implantation site in clinical practice. Yu and colleagues circumvent these issues and achieve stable diabetes reversal by transplanting islets encapsulated in a simple collagen-based matrix into the more accessible subcutaneous space.

    • Thierry Berney
    •  & Ekaterine Berishvili
  • News & Views |

    Cancer cells require exogenous cysteine for proliferation and survival. In this issue of Nature Metabolism, Zhang et al. demonstrate that deletion of 5-methylthioadenosine phosphorylase promotes the synthesis of polyamines from methionine, thereby conferring sensitivity to cysteine starvation.

    • Joseph A. Combs
    •  & Gina M. DeNicola
  • News & Views |

    The mechanistic target of rapamycin complex 1 (mTORC1) network integrates nutrient and energy signals that regulate metabolism and cell growth. Orozco et al. now show that the glycolytic intermediate dihydroxyacetone phosphate (DHAP) relays glycolytic activity to mTORC1 signalling.

    • Gerta Hoxhaj
    • , Jason W. Locasale
    •  & Issam Ben-Sahra
  • News & Views |

    GABA-expressing neurons in the arcuate nucleus of the hypothalamus regulate obesity in mice. A recent study indicates the importance of unexamined cell types.

    • Scott M. Sternson
  • News & Views |

    AMPK is a crucial sensor of the cellular energetic state and is also activated during glucose starvation. A new study reports that AMP-activated protein kinase (AMPK) is activated by interaction with long-chain fatty acyl–CoA esters, which appear to be the long-sought endogenous AMPK ligands that bind the allosteric drug and metabolite (ADaM) site.

    • D. Grahame Hardie
  • News & Views |

    Diet and exercise are the two pillars of a healthful lifestyle for stemming the rising tide of metabolic disease. A new study in this issue reveals that the health benefits of diet and aerobic exercise are more interdependent than previously appreciated, thus reinforcing the importance of a holistic approach to maintaining a healthful lifestyle.

    • Katja A. Lamia
  • News & Views |

    Caffa et al. report in Nature that hormone-receptor-positive breast cancer is sensitive to a form of ‘dietary augmentation therapy’ that implements periods of fasting, thus enhancing anti-cancer therapy.

    • Marcus D. Goncalves
    •  & Lewis C. Cantley
  • News & Views |

    A study published in this issue of Nature Metabolism adds to the emerging evidence that the small intestine is an initial site of dietary fructose metabolism, especially at low fructose doses, thus decreasing exposure of the liver and the colonic microbiome to intact fructose.

    • Marc Hellerstein
  • News & Views |

    Pancreatic adenocarcinoma (PDAC) is often characterized by substantial amounts of fibrosis, and how these stromal components affect metabolite availability is not fully understood. Zhu et al. now show that cancer-associated fibroblasts consume branched-chain amino acids (BCAAs) at high levels but release corresponding branched-chain α-ketoacids that support PDAC cell growth.

    • Russell E. Ericksen
    •  & Weiping Han
  • News & Views |

    The adipose tissue harbours multiple immune-cell types whose populations are known to be altered in disease conditions. A new study by Brigger et al. shows that restocking fat tissues of old mice with eosinophils prevents age-related declines in physical and immunological functions.

    • Chih-Hao Lee
  • News & Views |

    Selenium is a micronutrient essential for the generation of selenoproteins, which function predominantly by detoxifying cellular reactive oxygen species. In this issue, Carlisle et al. describe a novel mechanism whereby perturbing selenium utilization via inhibition of SEPHS2, a component of the selenocysteine-biosynthesis pathway, results in selenide poisoning and cancer cell death.

    • Anastasia Kapara
    • , Alessandro Vannini
    •  & Barrie Peck
  • News & Views |

    Maternal exercise during pregnancy results in metabolic benefits for offspring, but how mothers transfer these benefits to newborns has been a mystery. A new study now shows that a breast-milk component transmits the metabolic effects of exercise to offspring

    • Jose B. N. Moreira
    •  & Ulrik Wisløff
  • Editorial |

    The SARS-CoV-2 pandemic has posed one of the greatest scientific challenges to our society in a century. The accompanying disruption will have a disproportionally large effect on the careers of early-stage investigators and will require concrete action to preserve a generation of scientists.

  • Obituary |

    We have lost a distinguished biochemist who dedicated his career to the study of phosphatidylinositol signalling in metabolic regulation and to the advancement of lipidomics.

    • Friedrich Spener
    • , Christian Wolfrum
    •  & Wolf Reik
  • News & Views |

    Whereas textbooks depict metabolism in perfect homeostasis, disturbances occur in real life. One particularly relevant disturbance, caused by excess food and alcohol consumption and exacerbated by genetics, is reductive stress. New work by Goodman et al. identifies a biomarker of reductive stress and uses a gene therapy solution in mice. This work suggests how exercise and an accessible nutritional technology can synergistically increase catabolism and relieve reductive stress.

    • Collin D. Heer
    •  & Charles Brenner
  • News & Views |

    Thermogenic adipocytes can burn lipids and carbohydrates for heat generation. The finding that a primate-specific long non-coding RNA regulates lipolysis and respiration in thermogenic adipocytes reveals a new mechanism controlling thermogenic adipocyte metabolism in humans.

    • Dan Xu
    •  & Lei Sun
  • Comment |

    As the metabolism community has grown and diversified with scientists from multidisciplinary backgrounds, metabolic terminology has evolved and expanded. In this Comment, we reflect on this new vernacular and how established terminology can guide future discussions of metabolic research.

    • Mary-Ellen Harper
    •  & Mary-Elizabeth Patti
  • News & Views |

    Exposure to high glucose under inflammatory conditions is detrimental to insulin-secreting beta cells in the pancreas. Fu and colleagues describe a metabolic axis that decreases production of the ‘danger molecule’ nitric oxide and improves the survival of beta cells exposed to an inflammatory milieu, thus paving the way to new interventions for diabetes.

    • Christian Frezza
  • News & Views |

    Maintaining cellular NAD levels through supplementation with intermediates of NAD synthesis has considerable health benefits. A new study demonstrates that the reduced form of nicotinamide riboside, NRH, can be converted to NAD in a biosynthetic pathway that involves adenosine kinase, thus strongly boosting NAD levels in cells and tissues.

    • Mathias Ziegler
    •  & Andrey A. Nikiforov
  • News & Views |

    Fructose, a monosaccharide derived from fruits, is primarily consumed in a form combined with glucose as sugar or as a component of high-fructose corn syrup added as a sweetener to processed foods and carbonated beverages. Increased consumption of fructose has emerged as a major contributor to non-alcoholic fatty liver disease, dyslipidaemia, insulin resistance and diabetes. Now Zhao et al. show that hepatic lipid synthesis is increased by fructose metabolism in both the liver and intestine.

    • Catherine Postic
  • News & Views |

    Macrophages are required for postinjury skeletal muscle regeneration. A new study reveals that proinflammatory macrophages produce meteorin-like, which promotes muscle stem cell expansion through the Stat3–IGF1 axis and then shifts their inflammatory profile to allow return to homeostasis.

    • Bénédicte Chazaud
  • News & Views |

    By introducing a rationally designed metabolic pathway into the genome of Escherichia coli, Kim et al. have re-engineered central carbon metabolism to utilize the one-carbon intermediates formate and methanol for the first time, thus generating a biological platform for sustainable fuel and chemical production.

    • Mary E. Lidstrom
    •  & Jue Wang
  • News & Views |

    A recent study by Yuan et al., published in Nature Genetics, demonstrates multidimensional molecular alterations in mitochondrial DNA in human cancers and provides an online catalogue of mitochondrial genomes in many cancer types.

    • Wei Wei
    •  & Patrick F. Chinnery
  • News & Views |

    Current pharmacological options for diabetes treatment help patients control blood glucose levels but do not reverse the decline in insulin-secreting β-cells. A new study now shows that a pharmacological combination of insulin and a GLP-1–oestrogen conjugate not only decreases daily insulin requirements but also improves β-cell function.

    • Dario F. De Jesus
    •  & Rohit N. Kulkarni
  • News & Views |

    Inherited deficiencies in oxidative phosphorylation cause severe mitochondrial disease. A recent study in Nature Biotechnology demonstrates that an engineered bifunctional enzyme can rescue the biochemical consequences of mitochondrial dysfunction.

    • Rubén Zapata-Pérez
    •  & Riekelt H. Houtkooper
  • Comment |

    We are approaching the 100th anniversary of Otto Warburg’s first description of the metabolic phenotype bearing his name—a propensity for tumours to metabolize glucose anaerobically rather than aerobically, even when oxygen is available. Generations of scientists have studied the Warburg effect, yet misconceptions persist about its causes and relationship to oxidative metabolism in the mitochondria. Here, we review the definition of the Warburg effect and discuss its place within a modern understanding of cancer biology.

    • Ralph J. DeBerardinis
    •  & Navdeep S. Chandel
  • Editorial |

    As we celebrate 1 year at Nature Metabolism, we are grateful for the positive reception from our research community, and we reflect on the past 12 months and on what lies ahead.

  • News & Views |

    New research in this issue of Nature Metabolism shows how a high-protein diet increases amino acids in blood and atherosclerotic plaques, and in plaque macrophages activates mTOR signalling, suppresses mitophagy and increases apoptosis, thereby exacerbating atherosclerotic-plaque build-up in genetically modified mouse models.

    • Hanrui Zhang
    •  & Muredach P. Reilly
  • News & Views |

    Extracellular-matrix remodelling contributes to tumour progression, results in intratumoural fibrosis and promotes metastatic behaviour. A new study by Papalazarou et al. now reveals that a pathway involved in ATP supply, the creatine phosphagen system, is a mechanosensitive target during pancreatic cancer invasion.

    • Maria V. Liberti
    •  & Kivanc Birsoy
  • News & Views |

    Under a high-fat diet, the amyloid precursor protein, which is involved in the development of Alzheimer’s disease, accumulates at the protein-entry gate of mitochondria in white adipose tissue, thus leading to mitochondrial dysfunction, adipocyte hypertrophy and obesity.

    • Jiyao Song
    •  & Thomas Becker
  • News & Views |

    GDF15 is an anorectic hormone that relays systemic stress to the brain. In the current issue of Nature Metabolism, Day et al. elegantly demonstrate that the frontline anti-diabetes drug, metformin, lowers body weight by increasing circulating levels of GDF15.

    • Maximilian Kleinert
    •  & Timo D. Müller
  • News & Views |

    Di Gioia and colleagues report on how the oxidized phospholipid oxPAPC alters metabolism in macrophages via glutamine and oxaloacetate, thus boosting production of the cytokine IL-1β and promoting atherosclerosis.

    • Luke A. J. O’Neill
  • News & Views |

    A study in Nature Metabolism reveals a hitherto-unknown enzymatic and physiological role of ABHD5, which acts as a protease that couples extracellular cues to the epigenome of cardiomyocytes by cleaving histone deacetylase 4 (HDAC4).

    • Joshua G. Travers
    •  & Timothy A. McKinsey
  • News & Views |

    A new study by Menegaz et al. in this issue of Nature Metabolism addresses fundamental questions on the acute regulation and role of GABA secretion in pancreatic islets.

    • Guy A. Rutter
  • Comment |

    Nonalcoholic fatty liver disease (NAFLD) has emerged as the most prevalent liver disease worldwide, mainly because of the massive parallel global increase in obesity. Extensive public-health and political efforts will be needed in the near future to counteract this disturbing development.

    • Anna Mae Diehl
    • , Nathalie J. Farpour-Lambert
    • , Liping Zhao
    •  & Herbert Tilg
  • News & Views |

    The mechanism of alcohol-induced changes in the brain is multi-faceted. Acetate, the product of hepatic alcohol metabolism, might contribute to addictive behaviour by regulating gene expression.

    • Alia Ghrayeb
    • , Eyal Gottlieb
    •  & Inbal Mor
  • News & Views |

    Lifespan is increased and ageing is delayed by lifelong dietary restriction. A study in Nature Metabolism shows that these benefits are reduced when dietary restriction is started in old age, owing to the development of an inflexible nutritional memory within white adipose tissue.

    • Stephen J. Simpson
    •  & David G. Le Couteur
  • Editorial |

    A collaborative effort is required by individual scientists, research institutes and funding organizations towards the curation of high-quality, diverse metabolic data for the metabolism community to leverage the full potential of artificial intelligence.

  • News & Views |

    Nuclear DNA damage has detrimental effects on cellular homoeostasis and accelerates the ageing process. A new study causally links error-prone mitochondrial replication to increased nuclear DNA damage, thus suggesting that the hallmarks of ageing are associated with nuclear genome instability, a potential unifying denominator in the ageing process.

    • Björn Schumacher
    •  & Jan Vijg
  • News & Views |

    GDF15 is an anorectic hormone that signals organismal stress to the brain. New data suggest that GDF15 enhances tolerance to acute inflammation by modulating liver lipid metabolism and triglyceride availability in mice.

    • Samuel M. Lockhart
    •  & Stephen O’Rahilly
  • News & Views |

    Findeisen et al. have engineered IC7Fc, a cytokine for the treatment of type 2 diabetes, that selectively activates beneficial metabolic pathways systemically and in metabolic tissues without promoting an inflammatory response.

    • Marc Y. Donath
  • News & Views |

    Obesity is the result of an imbalance between caloric intake from the diet and energy expenditure. A new study provides evidence that alterations in calcium transport efficiency in muscle lead to an increased metabolic rate and protect mice against diet-induced obesity.

    • Fangfei Li
    •  & Muthu Periasamy