Browse Articles

  • Letter |

    Here the authors report the results of a first-in-human trial with urolithin A in healthy elderly individuals, demonstrating that the compound is well tolerated and bioavailable after oral administration. They also provide clinical data indicating that urolithin A may improve mitochondrial and cellular health in human muscle.

    • Pénélope A. Andreux
    • , William Blanco-Bose
    • , Dongryeol Ryu
    • , Frédéric Burdet
    • , Mark Ibberson
    • , Patrick Aebischer
    • , Johan Auwerx
    • , Anurag Singh
    •  & Chris Rinsch
  • Article |

    Non-alcoholic steatosis is characterized by lipid accumulation within hepatocytes and can progress to NASH. Haas and colleagues demonstrate that livers from people with NASH show a distinct but reversible gene profile from simple steatosis and accumulation of intrahepatic cDC and CD8 T cells.

    • Joel T. Haas
    • , Luisa Vonghia
    • , Denis A. Mogilenko
    • , An Verrijken
    • , Olivier Molendi-Coste
    • , Sébastien Fleury
    • , Audrey Deprince
    • , Artemii Nikitin
    • , Eloïse Woitrain
    • , Lucie Ducrocq-Geoffroy
    • , Samuel Pic
    • , Bruno Derudas
    • , Hélène Dehondt
    • , Céline Gheeraert
    • , Luc Van Gaal
    • , Ann Driessen
    • , Philippe Lefebvre
    • , Bart Staels
    • , Sven Francque
    •  & David Dombrowicz
  • Article |

    In this study, the authors use ATAC-seq and promoter capture Hi-C data from human adipocytes treated with fatty acids to identify gene–environment (G×E) interactions that influence body-mass index in humans. They report 154 genes that respond to saturated fat and discover 38 new G×E variants for body-mass index in data from the UK Biobank.

    • Kristina M. Garske
    • , David Z. Pan
    • , Zong Miao
    • , Yash V. Bhagat
    • , Caroline Comenho
    • , Christopher R. Robles
    • , Jihane N. Benhammou
    • , Marcus Alvarez
    • , Arthur Ko
    • , Chun Jimmie Ye
    • , Joseph R. Pisegna
    • , Karen L. Mohlke
    • , Janet S. Sinsheimer
    • , Markku Laakso
    •  & Päivi Pajukanta
  • Metabolic Messengers |

    The gut hormone FGF19 and its mouse orthologue Fgf15 are important mediators of the metabolic transition between the fasted and fed state. Here, Gadaleta and Moschetta provide a concise overview of the history of FGF15/FGF19, their physiological role and their molecular mechanism of action.

    • Raffaella Maria Gadaleta
    •  & Antonio Moschetta
  • Article |

    Bioproduct synthesis via reductive metabolism occurs with different efficiencies according to the availability of carbons, ATP and reducing agents. To maximize overall product synthesis efficiency, the authors develop a substrate cofeeding strategy, which circumvents catabolite repression and drives synergy in lipid synthesis from CO2 using two microbes.

    • Junyoung O. Park
    • , Nian Liu
    • , Kara M. Holinski
    • , David F. Emerson
    • , Kangjian Qiao
    • , Benjamin M. Woolston
    • , Jingyang Xu
    • , Zbigniew Lazar
    • , M. Ahsanul Islam
    • , Charles Vidoudez
    • , Peter R. Girguis
    •  & Gregory Stephanopoulos
  • Article |

    Pancreatic β-cells are highly connected, and this network is crucial for the pulsatile release of insulin. Here Salem and colleagues demonstrated the existence of leader β-cells that respond first to glucose and are more closely linked to the other β-cells. They also showed that glucose increases β-cell calcium dynamics and connectivity between the leader and non-leader β-cells.

    • Victoria Salem
    • , Luis Delgadillo Silva
    • , Kinga Suba
    • , Eleni Georgiadou
    • , S. Neda Mousavy Gharavy
    • , Nadeem Akhtar
    • , Aldara Martin-Alonso
    • , David C. A. Gaboriau
    • , Stephen M. Rothery
    • , Theodoros Stylianides
    • , Gaelle Carrat
    • , Timothy J. Pullen
    • , Sumeet Pal Singh
    • , David J. Hodson
    • , Isabelle Leclerc
    • , A. M. James Shapiro
    • , Piero Marchetti
    • , Linford J. B. Briant
    • , Walter Distaso
    • , Nikolay Ninov
    •  & Guy A. Rutter
  • Editorial |

    Awareness of non-alcoholic steatohepatitis (NASH) and its symptoms is essential for early detection, and an informed public is also more likely to take action against NASH development.

  • 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
  • Article |

    Iron homoeostasis is tightly orchestrated to avoid toxic iron overload. Here Lim and colleagues show that iron excess activates Nrf2 via mitochondrial reactive oxygen species, enhancing the expression of Bmp6 in liver sinusoidal endothelial cells, which in turn promotes hepcidin expression by hepatocytes, decreasing systemic iron levels.

    • Pei Jin Lim
    • , Tiago L. Duarte
    • , João Arezes
    • , Daniel Garcia-Santos
    • , Amel Hamdi
    • , Sant-Rayn Pasricha
    • , Andrew E. Armitage
    • , Hema Mehta
    • , Sarah Wideman
    • , Ana G. Santos
    • , Andreia Santos-Gonçalves
    • , Alireza Morovat
    • , Jim R. Hughes
    • , Elizabeth Soilleux
    • , Chia-Yu Wang
    • , Abraham L. Bayer
    • , Paul Klenerman
    • , Christian B. Willberg
    • , Richard C. Hartley
    • , Michael P. Murphy
    • , Jodie L. Babitt
    • , Prem Ponka
    • , Graça Porto
    •  & Hal Drakesmith
  • 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
  • Article |

    Here the authors demonstrate a mechanism by which PNPLA3 and its risk variant I148M contribute to intracellular lipid metabolism. PNPLA3 interacts with ABHD5 to prevent the PNPLA2–ABHD5 interaction, thereby inhibiting lipolysis in brown adipocytes and promoting lipid storage. The PNPLA3 I148M variant enhances this interaction.

    • Alexander Yang
    • , Emilio P. Mottillo
    • , Ljiljana Mladenovic-Lucas
    • , Li Zhou
    •  & James G. Granneman
  • Letter |

    Type 1 diabetes (T1D) involves immune-mediated destruction of pancreatic β cells. Here, the authors show that inducing β-cell replication before immune cell infiltration of the pancreas alters β-cell antigen expression and prevents T1D disease progression in female NOD mice in a regulatory-T-cell-dependent manner.

    • Ercument Dirice
    • , Sevim Kahraman
    • , Dario F. De Jesus
    • , Abdelfattah El Ouaamari
    • , Giorgio Basile
    • , Rocky L. Baker
    • , Burcu Yigit
    • , Paul D. Piehowski
    • , Mi-Jeong Kim
    • , Alexander J. Dwyer
    • , Raymond W. S. Ng
    • , Cornelia Schuster
    • , Heidrun Vethe
    • , Tijana Martinov
    • , Yuki Ishikawa
    • , Adrian Kee Keong Teo
    • , Richard D. Smith
    • , Jiang Hu
    • , Kathryn Haskins
    • , Thomas Serwold
    • , Wei-Jun Qian
    • , Brian T. Fife
    • , Stephan Kissler
    •  & Rohit N. Kulkarni
  • 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
  • Article |

    Metabolism is tightly regulated through communication among cells and organs. Here Gong and colleagues show that a liver-secreted factor, Gpnmb, promotes lipogenesis in adipose tissue and worsens metabolic dysfunctions during diet-induced obesity, whereas its inhibition reduces weight gain and insulin resistance.

    • Xue-Min Gong
    • , Yun-Feng Li
    • , Jie Luo
    • , Ji-Qiu Wang
    • , Jian Wei
    • , Ju-Qiong Wang
    • , Ting Xiao
    • , Chang Xie
    • , Jie Hong
    • , Guang Ning
    • , Xiong-Jie Shi
    • , Bo-Liang Li
    • , Wei Qi
    •  & Bao-Liang Song
  • 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
  • Article |

    Dietary protein influences metabolic health and ageing. Here Solon-Biet et al. show that, rather than having a direct toxic effect, dietary branched-chain amino acids (BCAAs) appear to induce hyperphagia, owing to an imbalance between BCAAs and other amino acids, which reduces lifespan as a consequence of obesity.

    • Samantha M. Solon-Biet
    • , Victoria C. Cogger
    • , Tamara Pulpitel
    • , Devin Wahl
    • , Ximonie Clark
    • , Elena E. Bagley
    • , Gabrielle C. Gregoriou
    • , Alistair M. Senior
    • , Qiao-Ping Wang
    • , Amanda E. Brandon
    • , Ruth Perks
    • , John O’Sullivan
    • , Yen Chin Koay
    • , Kim Bell-Anderson
    • , Melkam Kebede
    • , Belinda Yau
    • , Clare Atkinson
    • , Gunbjorg Svineng
    • , Tim Dodgson
    • , Jibran A. Wali
    • , Matthew D. W. Piper
    • , Paula Juricic
    • , Linda Partridge
    • , Adam J. Rose
    • , David Raubenheimer
    • , Gregory J. Cooney
    • , David G. Le Couteur
    •  & Stephen J. Simpson
  • Article |

    Activation of brown adipose tissue can ameliorate obesity and diabetes. Here the authors show that chemical inhibition of hyaluronan synthesis by 4‐methylumbelliferone or genetic deletion of hyaluronan synthases 2 and 3 decreases body-weight gain and improves glucose homeostasis by inducing the thermogenic capacity of brown adipose tissue in mice.

    • Maria Grandoch
    • , Ulrich Flögel
    • , Sam Virtue
    • , Julia K. Maier
    • , Tomas Jelenik
    • , Christina Kohlmorgen
    • , Kathrin Feldmann
    • , Yanina Ostendorf
    • , Tamara R. Castañeda
    • , Zhou Zhou
    • , Yu Yamaguchi
    • , Emmani B. M. Nascimento
    • , Vivekananda G. Sunkari
    • , Christine Goy
    • , Martina Kinzig
    • , Fritz Sörgel
    • , Paul L. Bollyky
    • , Patrick Schrauwen
    • , Hadi Al-Hasani
    • , Michael Roden
    • , Susanne Keipert
    • , Antonio Vidal-Puig
    • , Martin Jastroch
    • , Judith Haendeler
    •  & Jens W. Fischer
  • 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
  • Author Correction |

    • Martina Rauner
    • , Ulrike Baschant
    • , Antonella Roetto
    • , Rosa Maria Pellegrino
    • , Sandra Rother
    • , Juliane Salbach-Hirsch
    • , Heike Weidner
    • , Vera Hintze
    • , Graeme Campbell
    • , Andreas Petzold
    • , Regis Lemaitre
    • , Ian Henry
    • , Teresita Bellido
    • , Igor Theurl
    • , Sandro Altamura
    • , Silvia Colucci
    • , Martina U. Muckenthaler
    • , Georg Schett
    • , Davide S. K. Komla-Ebri
    • , J. H. Duncan Bassett
    • , Graham R. Williams
    • , Uwe Platzbecker
    •  & Lorenz C. Hofbauer
  • Editorial |

    The field of cellular metabolic research is growing but remains somewhat fragmented. Facilitating the exchange of ideas between cell biologists and the wider metabolism community will create synergies and further advance the field.

  • Letter |

    The transcription factor Klf15 controls various metabolic processes, including bile acid synthesis. Here the authors show that Klf15 acts as an upstream regulator of xenobiotic and endobiotic metabolism by controlling expression of a variety of phase I–III metabolic genes via direct and indirect mechanisms.

    • Shuxin Han
    • , Jonathan W. Ray
    • , Preeti Pathak
    • , David R. Sweet
    • , Rongli Zhang
    • , Huiyun Gao
    • , Nisha Jain
    • , Erik H. Koritzinsky
    • , Keiichiro Matoba
    • , Weixiong Xu
    • , E. Ricky Chan
    • , Daniel I. Simon
    •  & Mukesh K. Jain
  • 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
  • Article |

    Relapsed disease after conventional cancer treatments is an obstacle in epidermal growth factor receptor (EGFR)-based targeted therapy. Here the authors show that tolerance to the EGFR inhibitor osimertinib in non-small-cell lung cancer is mediated by the effects of miR-147b on the tricarboxylic acid cycle and pseudohypoxia pathways, which can be manipulated with a miR-147b inhibitor.

    • Wen Cai Zhang
    • , Julie M. Wells
    • , Kin-Hoe Chow
    • , He Huang
    • , Min Yuan
    • , Tanvi Saxena
    • , Mary Ann Melnick
    • , Katerina Politi
    • , John M. Asara
    • , Daniel B. Costa
    • , Carol J. Bult
    •  & Frank J. Slack
  • Article |

    Here the authors identify the long noncoding RNA lnc-ob1 as a regulator of osteoblast activity. Increased lnc-ob1 expression in osteoblasts, owing to either genetic knock-in or pharmacological delivery of a plasmid, increases bone formation and counteracts bone loss in an osteoporosis mouse model, thus suggesting that modulating lnc-ob1 expression may be therapeutically useful.

    • Yao Sun
    • , Mingxiang Cai
    • , Jiayong Zhong
    • , Li Yang
    • , Jia Xiao
    • , Fujun Jin
    • , Hui Xue
    • , Xiangning Liu
    • , Huisheng Liu
    • , Yongbiao Zhang
    • , Dong Jiang
    • , An Hong
    • , Xunming Ji
    • , Zuolin Wang
    • , Gong Zhang
    •  & Xiaogang Wang
  • Author Correction |

    • Cecilia Morgantini
    • , Jennifer Jager
    • , Xidan Li
    • , Laura Levi
    • , Valerio Azzimato
    • , André Sulen
    • , Emelie Barreby
    • , Connie Xu
    • , Michaela Tencerova
    • , Erik Näslund
    • , Chanchal Kumar
    • , Francisco Verdeguer
    • , Sara Straniero
    • , Kjell Hultenby
    • , Niklas K. Björkström
    • , Ewa Ellis
    • , Mikael Rydén
    • , Claudia Kutter
    • , Tracey Hurrell
    • , Volker M. Lauschke
    • , Jeremie Boucher
    • , Aleš Tomčala
    • , Gabriela Krejčová
    • , Adam Bajgar
    •  & Myriam Aouadi
  • 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
  • Article |

    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.

    • Cecilia Morgantini
    • , Jennifer Jager
    • , Xidan Li
    • , Laura Levi
    • , Valerio Azzimato
    • , André Sulen
    • , Emelie Barreby
    • , Connie Xu
    • , Michaela Tencerova
    • , Erik Näslund
    • , Chanchal Kumar
    • , Francisco Verdeguer
    • , Sara Straniero
    • , Kjell Hultenby
    • , Niklas K. Björkström
    • , Ewa Ellis
    • , Mikael Rydén
    • , Claudia Kutter
    • , Tracey Hurrell
    • , Volker M. Lauschke
    • , Jeremie Boucher
    • , Aleš Tomčala
    • , Gabriela Krejčová
    • , Adam Bajgar
    •  & Myriam Aouadi
  • Article |

    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.

    • Youqiong Ye
    • , Qingsong Hu
    • , Hu Chen
    • , Ke Liang
    • , Yuan Yuan
    • , Yu Xiang
    • , Hang Ruan
    • , Zhao Zhang
    • , Anren Song
    • , Huiwen Zhang
    • , Lingxiang Liu
    • , Lixia Diao
    • , Yanyan Lou
    • , Bingying Zhou
    • , Li Wang
    • , Shengtao Zhou
    • , Jianjun Gao
    • , Eric Jonasch
    • , Steven H. Lin
    • , Yang Xia
    • , Chunru Lin
    • , Liuqing Yang
    • , Gordon B. Mills
    • , Han Liang
    •  & Leng Han
  • Metabolic Messengers |

    Secreted from adipocytes, adiponectin exerts primarily anti-apoptotic, antiinflammatory, anti-fibrotic and insulin-sensitizing activities on multiple tissues. Here, Straub and Scherer provide a concise overview of the history of adiponectin, its physiological role and molecular mechanism of action.

    • Leon G. Straub
    •  & Philipp E. Scherer
  • Editorial |

    This month, we introduce a new series of articles, called Metabolic Messengers, dedicated to molecules involved in cellular communication and inter-tissue cross-talk.

  • Article |

    The oxidative pentose-phosphate pathway (oxPPP) is a major NADPH producer. Here the authors show that malic enzyme or isocitrate dehydrogenase can support the growth of cells lacking the oxPPP, but the oxPPP is necessary to maintain a normal NADPH/NADP ratio, DHFR activity and folate metabolism.

    • Li Chen
    • , Zhaoyue Zhang
    • , Atsushi Hoshino
    • , Henry D. Zheng
    • , Michael Morley
    • , Zoltan Arany
    •  & Joshua D. Rabinowitz
  • Article |

    Amino acids are required for cell survival and growth. However, the different requirements of amino acid metabolic pathways in normal haematopoiesis and leukaemogenesis have not been explored. Here the authors focus on the transporter of neutral amino acids and show that malignant blood cells rely more on ASCT2-mediated amino acid metabolism than normal cells.

    • Fang Ni
    • , Wen-Mei Yu
    • , Zhiguo Li
    • , Douglas K. Graham
    • , Lingtao Jin
    • , Sumin Kang
    • , Michael R. Rossi
    • , Shiyong Li
    • , Hal E. Broxmeyer
    •  & Cheng-Kui Qu
  • 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
  • Review Article |

    The protein kinase complex mechanistic target of rapamycin complex 1 (mTORC1) is a key cellular nutrient and energy sensor that integrates several inputs to regulate cell growth. Here, the authors discuss the molecular logic of the mTORC1 signalling network and its importance in coupling growth signals to the control of cellular metabolism.

    • Alexander J. Valvezan
    •  & Brendan D. Manning
  • Perspective |

    Activation of tissue-resident myeloid cells in the brain, known as microglia, is thought to drive obesity-associated hypothalamic dysfunction. The authors of this Perspective present a more nuanced view of microglia, echoing lessons learned from the field of adipose macrophage biology: instead of simply responding to diet-induced damage, microglia are proposed to act as nutrient and environmental sensors that regulate hypothalamic physiology, a role that, if hijacked by chronic overnutrition, can produce disease.

    • Martin Valdearcos
    • , Martin G. Myers Jr
    •  & Suneil K. Koliwad
  • Article |

    Obesity is associated with an increased risk of colitis-associated cancer (CAC). Here Ostermann et al. show that a high-fat diet induces insulin resistance in intestinal epithelial cells (IECs) and that genetic inactivation of insulin and IGF1 signalling in IECs impairs intestinal regeneration and enhances tumour formation in a CAC mouse model.

    • A. L. Ostermann
    • , C. M. Wunderlich
    • , L. Schneiders
    • , M. C. Vogt
    • , M. A. Woeste
    • , B. F. Belgardt
    • , C. M. Niessen
    • , B. Martiny
    • , A. C. Schauss
    • , P. Frommolt
    • , A. Nikolaev
    • , N. Hövelmeyer
    • , R. C. Sears
    • , P. J. Koch
    • , D. Günzel
    • , J. C. Brüning
    •  & F. T. Wunderlich
  • 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
  • Letter |

    AMPK is a master regulator of cellular metabolism. Here the authors show that a constitutively active AMPK mutation protects mice fed a high-fat diet from obesity by increasing energy expenditure in subcutaneous white adipocytes, possibly as a result of the emergence of a hitherto-unknown type of adipocyte.

    • Alice E. Pollard
    • , Luís Martins
    • , Phillip J. Muckett
    • , Sanjay Khadayate
    • , Aurélie Bornot
    • , Maryam Clausen
    • , Therese Admyre
    • , Mikael Bjursell
    • , Rebeca Fiadeiro
    • , Laura Wilson
    • , Chad Whilding
    • , Vassilios N. Kotiadis
    • , Michael R. Duchen
    • , Daniel Sutton
    • , Lucy Penfold
    • , Alessandro Sardini
    • , Mohammad Bohlooly-Y
    • , David M. Smith
    • , Jon A. Read
    • , Michael A. Snowden
    • , Angela Woods
    •  & David Carling
  • Article |

    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.

    • Lawrence Kazak
    • , Janane F. Rahbani
    • , Bozena Samborska
    • , Gina Z. Lu
    • , Mark P. Jedrychowski
    • , Mathieu Lajoie
    • , Song Zhang
    • , LeeAnn Ramsay
    • , Florence Y. Dou
    • , Danielle Tenen
    • , Edward T. Chouchani
    • , Petras Dzeja
    • , Ian R. Watson
    • , Linus Tsai
    • , Evan D. Rosen
    •  & Bruce M. Spiegelman
  • Letter |

    Olfactory food perception is known to extend lifespan in C. elegans. Here the authors demonstrate food-odour-dependent brain-to-gut communication that extends lifespan in worms. Food odour downregulates tir-1 mRNA in AWC neurons, in a manner dependent on the miRNA miR-71, which triggers downstream effects in the gut, due to neuropeptide secretion, that promote proteostasis and longevity.

    • Fabian Finger
    • , Franziska Ottens
    • , Alexander Springhorn
    • , Tanja Drexel
    • , Lucie Proksch
    • , Sophia Metz
    • , Luisa Cochella
    •  & Thorsten Hoppe
  • Review Article |

    Like stem cells, cancer cells can rapidly proliferate but, unlike stem cells, they are mostly locked into a malignant identity. Here, Finley and Intlekofer highlight commonalities in anabolic pathways that support proliferation in cancer and stem cells, and point out unique metabolic features that influence self-renewal and differentiation.

    • Andrew M. Intlekofer
    •  & Lydia W. S. Finley
  • Article |

    Many beneficial effects of exercise are mediated by factors secreted from the exercising muscle, so-called myokines. Here, the authors identify what might be the first exercised-induced adipokine, TGF-β2, which is secreted from subcutaneous fat in response to exercise-induced increases in serum lactate levels and has beneficial metabolic effects in mice.

    • Hirokazu Takahashi
    • , Christiano R. R. Alves
    • , Kristin I. Stanford
    • , Roeland J. W. Middelbeek
    • , Pasquale Nigro
    • , Rebecca E. Ryan
    • , Ruidan Xue
    • , Masaji Sakaguchi
    • , Matthew D. Lynes
    • , Kawai So
    • , Joram D. Mul
    • , Min-Young Lee
    • , Estelle Balan
    • , Hui Pan
    • , Jonathan M. Dreyfuss
    • , Michael F. Hirshman
    • , Mohamad Azhar
    • , Jarna C. Hannukainen
    • , Pirjo Nuutila
    • , Kari K. Kalliokoski
    • , Søren Nielsen
    • , Bente K. Pedersen
    • , C. Ronald Kahn
    • , Yu-Hua Tseng
    •  & Laurie J. Goodyear
  • Letter |

    Neurons and astrocytes cooperate metabolically but differ in key aspects of their metabolism, including the production of mitochondrial reactive oxygen species (ROS). Here, the authors show that mitochondrial ROS produced in astrocytes affect neuronal metabolism and mouse memory and behaviour.

    • Carlos Vicente-Gutierrez
    • , Nicoló Bonora
    • , Veronica Bobo-Jimenez
    • , Daniel Jimenez-Blasco
    • , Irene Lopez-Fabuel
    • , Emilio Fernandez
    • , Charlene Josephine
    • , Gilles Bonvento
    • , Jose A. Enriquez
    • , Angeles Almeida
    •  & Juan P. Bolaños
  • News & Views |

    Hypothalamic neuronal diversity is at the core of whole-body energy-homeostasis control, but the molecular mechanisms governing neuronal neuropeptide specification remain incompletely understood. A new study in Nature Metabolism adds a relevant piece to the puzzle of how key hypothalamic neuronal populations maintain their peptidergic identity throughout the lifespan.

    • Arnaud Obri
    •  & Marc Claret
  • Article |

    Hypothalamic melanocortin neurons control energy homoeostasis by modulating appetite. Here, the authors reveal a role for the transcription factor Tbx3 as a regulator of the peptidergic identity and function of immature and mature mouse melanocortin neurons.

    • Carmelo Quarta
    • , Alexandre Fisette
    • , Yanjun Xu
    • , Gustav Colldén
    • , Beata Legutko
    • , Yu-Ting Tseng
    • , Alexander Reim
    • , Michael Wierer
    • , Maria Caterina De Rosa
    • , Valentina Klaus
    • , Rick Rausch
    • , Vidhu V. Thaker
    • , Elisabeth Graf
    • , Tim M. Strom
    • , Anne-Laure Poher
    • , Tim Gruber
    • , Ophélia Le Thuc
    • , Alberto Cebrian-Serrano
    • , Dhiraj Kabra
    • , Luigi Bellocchio
    • , Stephen C. Woods
    • , Gert O. Pflugfelder
    • , Rubén Nogueiras
    • , Lori Zeltser
    • , Ilona C. Grunwald Kadow
    • , Anne Moon
    • , Cristina García-Cáceres
    • , Matthias Mann
    • , Mathias Treier
    • , Claudia A. Doege
    •  & Matthias H. Tschöp