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    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
  • 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
  • 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
  • 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
  • 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
  • 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
  • News & Views |

    Systemic accumulation of branched-chain amino acids (BCAAs) is a major metabolic hallmark and contributor to insulin resistance associated with obesity. A recent report identifies SLC25A44 as the BCAA transporter in mitochondrial membranes and shows that BCAA catabolism in brown adipose tissue significantly affects thermogenic activity, systemic BCAA clearance, energy expenditure and overall metabolic health.

    • Haipeng Sun
    •  & Yibin Wang
  • News & Views |

    Dopamine is an important neurotransmitter with essential roles in movement control and salience, and implications in addiction as well as weight loss, decreased food intake and a reduced motivational drive to eat. Folgueira et al. now demonstrate that dopamine causes weight loss and increases brown adipose tissue temperature via activation of the dopamine receptor D2R in hypothalamic GABA-expressing neurons in mice, and treatment with the dopamine agonist cabergoline causes weight loss in humans.

    • Stephanie E. Simonds
    •  & Michael A. Cowley
  • News & Views |

    Cells contributing to atherosclerotic disease are highly plastic and can shift their phenotype in a changing microenvironment. A study in Nature Metabolism now reveals that transforming growth factor-β (TGF-β) can transform endothelial cells into pro-inflammatory cells and that inhibition of TGF-β-receptor signalling in the endothelium can reverse atherosclerosis in mice.

    • Kathryn L. Howe
    •  & Jason E. Fish
  • News & Views |

    The gene encoding the RagC GTPase (RRAGC), an activator of a nutrient-sensing pathway that drives cellular anabolism, is mutated in 15% of follicular lymphoma cases. A new study provides evidence that RRAGC mutations promote lymphomagenesis by distorting the nutrient-dependent control of paracrine signals from the microenvironment, thus enhancing B-cell activation.

    • Ulf Klein
  • News & Views |

    Diabetes mellitus invariably involves impaired regulation of insulin secretion from pancreatic β cells, as a result of unfavourable environmental influences in combination with aberrant expression of risk genes at either the transcriptional or the translational level. A recent report in Nature Metabolism explores a novel role of mRNA methylation in β-cell function and suggests that its downregulation causes type 2 diabetes.

    • Erik Renström
    •  & Enming Zhang
  • News & Views |

    Lymphedema, a condition of fluid retention and tissue swelling, is currently incurable and is treated primarily with physical therapy. Studies in mice reveal that intake of a ketogenic diet or exogenous ketone bodies may alleviate lymphedema by increasing the formation of lymphatic vessels, which can drain excess lymph fluid.

    • Patrycja Puchalska
    •  & Peter A. Crawford
  • News & Views |

    The loss of T cell immune function as a result of human immunodeficiency virus (HIV) infection leads to opportunistic infections and certain HIV-associated cancers. Two recent studies shed light on the complex immunometabolic changes during HIV infection and open the door to metabolic treatment options that could ultimately cure HIV.

    • Ramon I. Klein Geltink
  • News & Views |

    The entry of remnants of cholesterol-rich lipoproteins, such as low-density lipoprotein (LDL), from the blood stream into the intima of large arteries initiates and then perpetuates atherosclerosis. A study published in Nature sheds new light on this important process by identifying scavenger receptor BI (SR-BI) as a major receptor that mediates LDL delivery across the endothelium into arteries.

    • Xinbo Zhang
    •  & Carlos Fernández-Hernando
  • News & Views |

    Living organisms face the dual challenge of acquiring enough iron to perform biological functions while preventing toxic iron accretion. A study now shows that sensing of iron-catalysed free radicals by a druggable gene-regulatory pathway helps the body avoid iron poisoning.

    • Sandro Altamura
    •  & Bruno Galy
  • News & Views |

    Interorgan communication is emerging as a critical contributor to nutrient and energy homeostasis. A new study has identified a secreted liver factor that stimulates lipid synthesis in white adipose tissue and exacerbates obesity and insulin resistance.

    • Henry Kuang
    •  & Jiandie D. Lin
  • News & Views |

    A common missense variant (I148M) in patatin-like phospholipase domain-containing protein 3 (PNPLA3) was strongly linked to human fatty liver disease in 2008, but the underlying mechanisms have since remained unclear. Compelling data from Yang et al., published in Nature Metabolism, suggest that PNPLA3 binds ABHD5, sequestering it and preventing it from activating ATGL, the major intracellular triglyceride lipase.

    • Stefano Romeo
    •  & David B. Savage
  • News & Views |

    Increasing pancreatic β-cell proliferation in autoimmune type 1 diabetes (T1D) might restore β-cell mass but would be predicted to exacerbate islet inflammation. A study in Nature Metabolism, however, reports that boosting β-cell proliferation in mouse models of T1D is beneficial, preserving the immunological self-tolerance of islets through the induction of regulatory T cells.

    • Mario Galgani
    •  & Giuseppe Matarese
  • News & Views |

    Obesity is a manifestation of a positive energy balance in which energy intake exceeds energy expenditure, thus often leading to insulin resistance and type 2 diabetes. A new study provides evidence that pharmacological inhibition of hyaluronan, an extracellular-matrix glycosaminoglycan, increases energy expenditure and insulin sensitivity by activating thermogenesis in brown adipose tissue.

    • Philip L. S. M. Gordts
    •  & Alan R. Saltiel
  • News & Views |

    Understanding the mechanisms by which tumour cells adapt or succumb to targeted therapies is crucial to improving cancer treatment. A study in this issue of Nature Metabolism demonstrates how microRNAs, metabolic pathways and pseudohypoxia play a major role in the drug tolerance to epidermal growth factor receptor (EGFR) inhibitors in lung adenocarcinoma.

    • George A. Calin
    •  & Barbara Pardini
  • News & Views |

    A recent large genetic study by Sanna et al., published in Nature Genetics, has shown that short-chain fatty acids, which are produced by gut microbes, have a significant causal effect on insulin secretion, postprandial glycaemic responses and risk of type 2 diabetes.

    • Cristina Menni
    •  & Ana M. Valdes
  • News & Views |

    As one of the most highly consumed amino acids in cultured cancer cells, glutamine is an attractive target for anti-cancer therapy, and glutaminase inhibitors are currently in clinical trials. In this issue, Ni et al. show that blocking this pathway by targeting the glutamine importer ASCT2 (SLC1A5) decreases tumorigenesis in mouse leukaemia models while largely sparing normal haematopoiesis.

    • Richard Possemato
  • News & Views |

    Patients with severe diabetes rely on insulin injections to control their blood glucose. A study now provides evidence that human cells that normally do not release insulin can be converted into insulin-producing cells that are able to normalize glycaemia in diabetic mice.

    • Mostafa Bakhti
    •  & Heiko Lickert
  • News & Views |

    The senescence-associated secretory phenotype (SASP) is responsible for the deleterious effects of senescent cells in ageing and cancer. A new study shows that NAD+ metabolism can regulate the pro-inflammatory SASP, thereby promoting tumorigenesis.

    • Pia Pernille Søgaard
    •  & Jesús Gil