Articles

  • Article |

    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.

    • Gurpreet S. Baht
    • , Akshay Bareja
    • , David E. Lee
    • , Rajesh R. Rao
    • , Rong Huang
    • , Janet L. Huebner
    • , David B. Bartlett
    • , Cory R. Hart
    • , Jason R. Gibson
    • , Ian R. Lanza
    • , Virginia B. Kraus
    • , Simon G. Gregory
    • , Bruce M. Spiegelman
    •  & James P. White
  • Article |

    Li and colleagues show how cMyc promotes tumourigenesis by promoting succinate dehydrogenase complex subunit A acetylation by activating SKP2-mediated degradation of SIRT3. This leads to succinate accumulation and consequent tumour-specific gene expression.

    • Shi-Ting Li
    • , De Huang
    • , Shengqi Shen
    • , Yongping Cai
    • , Songge Xing
    • , Gongwei Wu
    • , Zetan Jiang
    • , Yijie Hao
    • , Mengqiu Yuan
    • , Nana Wang
    • , Lianbang Zhu
    • , Ronghui Yan
    • , Dongdong Yang
    • , Lin Wang
    • , Zhaoji Liu
    • , Xin Hu
    • , Rongbin Zhou
    • , Kun Qu
    • , Ailing Li
    • , Xiaotao Duan
    • , Huafeng Zhang
    •  & Ping Gao
  • Article |

    Anhê et al. demonstrate that bacterial signatures of plasma, liver and three distinct adipose tissue depots can distinguish between type 2 diabetes and normoglycaemia in people with obesity.

    • Fernando F. Anhê
    • , Benjamin Anderschou Holbech Jensen
    • , Thibault V. Varin
    • , Florence Servant
    • , Sebastian Van Blerk
    • , Denis Richard
    • , Simon Marceau
    • , Michael Surette
    • , Laurent Biertho
    • , Benjamin Lelouvier
    • , Jonathan D. Schertzer
    • , André Tchernof
    •  & André Marette
  • Article |

    Parathyroid glands regulate calcium homeostasis by secreting parathyroid hormone. Chang et al. demonstrate that in parathyroid glands GABA receptor GABAB1R makes a heterocomplex with the calcium-sensing receptor and regulates the secretion of parathyroid hormone.

    • Wenhan Chang
    • , Chia-Ling Tu
    • , Frederic G. Jean-Alphonse
    • , Amanda Herberger
    • , Zhiqiang Cheng
    • , Jenna Hwong
    • , Hanson Ho
    • , Alfred Li
    • , Dawei Wang
    • , Hongda Liu
    • , Alex D. White
    • , Insoo Suh
    • , Wen Shen
    • , Quan-Yang Duh
    • , Elham Khanafshar
    • , Dolores M. Shoback
    • , Kunhong Xiao
    •  & Jean-Pierre Vilardaga
  • Article |

    Maintenance of NADPH levels during environmental stress can prolong cell survival. Ding et al. identify MESH1 as a cytosolic NADPH phosphatase that is required for the metabolic commitment to ferroptosis in cancer cell lines.

    • Chien-Kuang Cornelia Ding
    • , Joshua Rose
    • , Tianai Sun
    • , Jianli Wu
    • , Po-Han Chen
    • , Chao-Chieh Lin
    • , Wen-Hsuan Yang
    • , Kai-Yuan Chen
    • , Hana Lee
    • , Emily Xu
    • , Sarah Tian
    • , Jadesola Akinwuntan
    • , Jinshi Zhao
    • , Ziqiang Guan
    • , Pei Zhou
    •  & Jen-Tsan Chi
  • Article |

    Proliferation of cardiomyocytes typically ceases shortly after birth. Here the authors show that decreasing fatty-acid oxidation extends the perinatal cardiomyocyte proliferative window and can reintroduce cell-cycle activity in adult cardiomyocytes.

    • Alisson C. Cardoso
    • , Nicholas T. Lam
    • , Jainy J. Savla
    • , Yuji Nakada
    • , Ana Helena M. Pereira
    • , Abdallah Elnwasany
    • , Ivan Menendez-Montes
    • , Emily L. Ensley
    • , Ursa Bezan Petric
    • , Gaurav Sharma
    • , A. Dean Sherry
    • , Craig R. Malloy
    • , Chalermchai Khemtong
    • , Michael T. Kinter
    • , Wilson Lek Wen Tan
    • , Chukwuemeka G. Anene-Nzelu
    • , Roger Sik-Yin Foo
    • , Ngoc Uyen Nhi Nguyen
    • , Shujuan Li
    • , Mahmoud Salama Ahmed
    • , Waleed M. Elhelaly
    • , Salim Abdisalaam
    • , Aroumougame Asaithamby
    • , Chao Xing
    • , Mohammed Kanchwala
    • , Gonçalo Vale
    • , Kaitlyn M. Eckert
    • , Matthew A. Mitsche
    • , Jeffrey G. McDonald
    • , Joseph A. Hill
    • , Linzhang Huang
    • , Philip W. Shaul
    • , Luke I. Szweda
    •  & Hesham A. Sadek
  • Article |

    β-cell dedifferentiation has emerged as a contributing mechanism in type 1 and type 2 diabetes development. Here Sachs et al. show that a pharmacological treatment that combines insulin and a GLP-1–oestrogen conjugate reverses dedifferentiation, and improves β-cell function and hyperglycaemia in diabetic mice.

    • Stephan Sachs
    • , Aimée Bastidas-Ponce
    • , Sophie Tritschler
    • , Mostafa Bakhti
    • , Anika Böttcher
    • , Miguel A. Sánchez-Garrido
    • , Marta Tarquis-Medina
    • , Maximilian Kleinert
    • , Katrin Fischer
    • , Sigrid Jall
    • , Alexandra Harger
    • , Erik Bader
    • , Sara Roscioni
    • , Siegfried Ussar
    • , Annette Feuchtinger
    • , Burcak Yesildag
    • , Aparna Neelakandhan
    • , Christine B. Jensen
    • , Marion Cornu
    • , Bin Yang
    • , Brian Finan
    • , Richard D. DiMarchi
    • , Matthias H. Tschöp
    • , Fabian J. Theis
    • , Susanna M. Hofmann
    • , Timo D. Müller
    •  & Heiko Lickert
  • Article |

    Zuend and colleagues show that an arousal-induced increase in cortical activity is accompanied by a surge in lactate in the extracellular space and a substantial lactate dip in astrocytes, followed by mobilization of lactate from glycogen stores and neuronal lactate increase.

    • Marc Zuend
    • , Aiman S. Saab
    • , Matthias T. Wyss
    • , Kim David Ferrari
    • , Ladina Hösli
    • , Zoe J. Looser
    • , Jillian L. Stobart
    • , Jordi Duran
    • , Joan J. Guinovart
    • , L. Felipe Barros
    •  & Bruno Weber
  • Article |

    Hartl et al. demonstrate how metabolism and the cell cycle are coupled in prokaryotic cells by analysing the metabolome during the cell cycle in Caulobacter crescentus. Whereas the levels of most metabolites are independent of the cell cycle, glutathione fluctuates and is required for coordinated cell cycle progression.

    • Johannes Hartl
    • , Patrick Kiefer
    • , Andreas Kaczmarczyk
    • , Maximilian Mittelviefhaus
    • , Fabian Meyer
    • , Thomas Vonderach
    • , Bodo Hattendorf
    • , Urs Jenal
    •  & Julia A. Vorholt
  • Article |

    Zhang et al. show that high-protein diets increase atherosclerosis risk through macrophage mTORC1 activation associated with suppressed clearance of damaged mitochondria and increased apoptosis.

    • Xiangyu Zhang
    • , Ismail Sergin
    • , Trent D. Evans
    • , Se-Jin Jeong
    • , Astrid Rodriguez-Velez
    • , Divya Kapoor
    • , Sunny Chen
    • , Eric Song
    • , Karyn B. Holloway
    • , Jan R. Crowley
    • , Slava Epelman
    • , Conrad C. Weihl
    • , Abhinav Diwan
    • , Daping Fan
    • , Bettina Mittendorfer
    • , Nathan O. Stitziel
    • , Joel D. Schilling
    • , Irfan J. Lodhi
    •  & Babak Razani
  • Article |

    The ketogenic diet is a low-carbohydrate, high-fat diet that forces a metabolic switch towards fatty acid oxidation. Here, Goldberg et al. show that a ketogenic diet initially improves metabolic health and expands adipose tissue γδ T cells that are important for glycaemic control during obesity.

    • Emily L. Goldberg
    • , Irina Shchukina
    • , Jennifer L. Asher
    • , Sviatoslav Sidorov
    • , Maxim N. Artyomov
    •  & Vishwa Deep Dixit
  • Article |

    Extracellular-matrix remodelling promotes tumour progression and metastasis. Papalazarou et al. demonstrate that mechanosensing affects pancreatic cancer cell migration, metabolism and ultimately metastatic potential by targeting the creatine–phosphagen ATP-recycling system.

    • Vassilis Papalazarou
    • , Tong Zhang
    • , Nikki R. Paul
    • , Amelie Juin
    • , Marco Cantini
    • , Oliver D. K. Maddocks
    • , Manuel Salmeron-Sanchez
    •  & Laura M. Machesky
  • Article |

    Converting serine to pyruvate and ammonia, serine racemase is shown to support colon-cancer growth, thus highlighting a new strategy that cancer cells use to maintain cellular pyruvate levels and mitochondrial mass.

    • Kenji Ohshima
    • , Satoshi Nojima
    • , Shinichiro Tahara
    • , Masako Kurashige
    • , Keisuke Kawasaki
    • , Yumiko Hori
    • , Moyu Taniguchi
    • , Yutaka Umakoshi
    • , Daisuke Okuzaki
    • , Naoki Wada
    • , Jun-ichiro Ikeda
    • , Eiichiro Fukusaki
    •  & Eiichi Morii
  • Article |

    Adipose tissue varies depending on localization. Vijay et al. perform single-cell RNA sequencing in multiple adipose tissue depots from obese individuals and identify distinct subpopulations of endothelial cells, immune cells and pre-adipocytes.

    • Jinchu Vijay
    • , Marie-Frédérique Gauthier
    • , Rebecca L. Biswell
    • , Daniel A. Louiselle
    • , Jeffrey J. Johnston
    • , Warren A. Cheung
    • , Bradley Belden
    • , Albena Pramatarova
    • , Laurent Biertho
    • , Margaret Gibson
    • , Marie-Michelle Simon
    • , Haig Djambazian
    • , Alfredo Staffa
    • , Guillaume Bourque
    • , Anita Laitinen
    • , Johanna Nystedt
    • , Marie-Claude Vohl
    • , Jason D. Fraser
    • , Tomi Pastinen
    • , André Tchernof
    •  & Elin Grundberg
  • Article |

    Amyloid precursor protein contributes to the pathogenesis of Alzheimer’s disease. An et al. show that its increase in white adipose tissue under a high-fat diet promotes obesity and impairs mitochondrial function by blocking the protein import machinery.

    • Yu A. An
    • , Clair Crewe
    • , Ingrid Wernstedt Asterholm
    • , Kai Sun
    • , Shiuhwei Chen
    • , Fang Zhang
    • , Mengle Shao
    • , Jan-Bernd Funcke
    • , Zhuzhen Zhang
    • , Leon Straub
    • , Jun Yoshino
    • , Samuel Klein
    • , Christine M. Kusminski
    •  & Philipp E. Scherer
  • Article |

    Bevers and Litovchenko et al. sequence mitochondrial genomes from 169 different inbred Drosophila melanogaster strains to reveal mitochondrial population structure as well as links between mitochondrial haplotypes and metabolic variation in flies.

    • Roel P. J. Bevers
    • , Maria Litovchenko
    • , Adamandia Kapopoulou
    • , Virginie S. Braman
    • , Matthew R. Robinson
    • , Johan Auwerx
    • , Brian Hollis
    •  & Bart Deplancke
  • Article |

    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.

    • Danusa Menegaz
    • , D. Walker Hagan
    • , Joana Almaça
    • , Chiara Cianciaruso
    • , Rayner Rodriguez-Diaz
    • , Judith Molina
    • , Robert M. Dolan
    • , Matthew W. Becker
    • , Petra C. Schwalie
    • , Rita Nano
    • , Fanny Lebreton
    • , Chen Kang
    • , Rajan Sah
    • , Herbert Y. Gaisano
    • , Per-Olof Berggren
    • , Steinunn Baekkeskov
    • , Alejandro Caicedo
    •  & Edward A. Phelps
  • Article |

    Known as a regulator of lipolysis, ABHD5 is found to also act as a serine protease that cleaves HDAC4 in response to catecholaminergic stimulation, thus resulting in the formation of a polypeptide that protects against metabolic-stress-induced heart failure.

    • Zegeye H. Jebessa
    • , Kumar D. Shanmukha
    • , Matthias Dewenter
    • , Lorenz H. Lehmann
    • , Chang Xu
    • , Friederike Schreiter
    • , Dominik Siede
    • , Xue-Min Gong
    • , Barbara C. Worst
    • , Giuseppina Federico
    • , Sven W. Sauer
    • , Tamas Fischer
    • , Lisa Wechselberger
    • , Oliver J. Müller
    • , Samuel Sossalla
    • , Christoph Dieterich
    • , Patrick Most
    • , Herrmann-Josef Gröne
    • , Cedric Moro
    • , Monika Oberer
    • , Guenter Haemmerle
    • , Hugo A. Katus
    • , Jens Tyedmers
    •  & Johannes Backs
  • Article |

    Liu et al. describe a molecular network wherein SIRT7 couples light-driven systemic body temperature cues to hepatic oscillators via HSP70 to ensure circadian phase coherence and glucose homeostasis in the liver.

    • Zuojun Liu
    • , Minxian Qian
    • , Xiaolong Tang
    • , Wenjing Hu
    • , Shimin Sun
    • , Guo Li
    • , Shuju Zhang
    • , Fanbiao Meng
    • , Xinyue Cao
    • , Jie Sun
    • , Cheng Xu
    • , Bing Tan
    • , Qiuxiang Pang
    • , Bosheng Zhao
    • , Zimei Wang
    • , Youfei Guan
    • , Xiongzhong Ruan
    •  & Baohua Liu
  • Article |

    Al Nabhani et al. show how excessive caloric intake during the postnatal period increases the risk of developing intestinal bowel disease during adulthood, owing to increased intestinal permeability, cytokines and hydrogen sulfide production by the microbiota.

    • Ziad Al Nabhani
    • , Sophie Dulauroy
    • , Emelyne Lécuyer
    • , Bernadette Polomack
    • , Pascal Campagne
    • , Marion Berard
    •  & Gérard Eberl
  • Article |

    Emerging findings identify important roles for brain lipoprotein receptors in the control of whole-body energy homoeostasis. Here Lee et al. reveal that IDOL-mediated regulation of VLDLR abundance in neurons, but not in peripheral metabolic tissues, regulates food intake and energy expenditure.

    • Stephen D. Lee
    • , Christina Priest
    • , Mikael Bjursell
    • , Jie Gao
    • , Douglas V. Arneson
    • , In Sook Ahn
    • , Graciel Diamante
    • , J. Edward van Veen
    • , Megan G. Massa
    • , Anna C. Calkin
    • , Jason Kim
    • , Harriet Andersén
    • , Prashant Rajbhandari
    • , Michelle Porritt
    • , Alba Carreras
    • , Andrea Ahnmark
    • , Frank Seeliger
    • , Ingela Maxvall
    • , Pernilla Eliasson
    • , Magnus Althage
    • , Peter Åkerblad
    • , Daniel Lindén
    • , Tracy A. Cole
    • , Richard Lee
    • , Helen Boyd
    • , Mohammad Bohlooly-Y
    • , Stephanie M. Correa
    • , Xia Yang
    • , Peter Tontonoz
    •  & Cynthia Hong
  • Article |

    Dietary restriction (DR) late in life does not improve survival and has little benefit in metabolic health in mice. The absence of a DR gene-expression signature in fat tissue suggests that a ‘nutritional memory’ interferes with the benefits of DR.

    • Oliver Hahn
    • , Lisa F. Drews
    • , An Nguyen
    • , Takashi Tatsuta
    • , Lisonia Gkioni
    • , Oliver Hendrich
    • , Qifeng Zhang
    • , Thomas Langer
    • , Scott Pletcher
    • , Michael J. O. Wakelam
    • , Andreas Beyer
    • , Sebastian Grönke
    •  & Linda Partridge
  • Article |

    In addition to having direct anti-cancer effects, the cardiac glycoside ouabain is shown to kill a broad range of senescent cells, thus suggesting that cardiac glycosides represent a novel class of senolytics.

    • Ana Guerrero
    • , Nicolás Herranz
    • , Bin Sun
    • , Verena Wagner
    • , Suchira Gallage
    • , Romain Guiho
    • , Katharina Wolter
    • , Joaquim Pombo
    • , Elaine E. Irvine
    • , Andrew J. Innes
    • , Jodie Birch
    • , Justyna Glegola
    • , Saba Manshaei
    • , Danijela Heide
    • , Gopuraja Dharmalingam
    • , Jule Harbig
    • , Antoni Olona
    • , Jacques Behmoaras
    • , Daniel Dauch
    • , Anthony G. Uren
    • , Lars Zender
    • , Santiago Vernia
    • , Juan Pedro Martínez-Barbera
    • , Mathias Heikenwalder
    • , Dominic J. Withers
    •  & Jesús Gil
  • Article |

    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.

    • Susanne Seitz
    • , Yun Kwon
    • , Götz Hartleben
    • , Julia Jülg
    • , Revathi Sekar
    • , Natalie Krahmer
    • , Bahar Najafi
    • , Anne Loft
    • , Sofiya Gancheva
    • , Kerstin Stemmer
    • , Annette Feuchtinger
    • , Martin Hrabe de Angelis
    • , Timo D. Müller
    • , Matthias Mann
    • , Matthias Blüher
    • , Michael Roden
    • , Mauricio Berriel Diaz
    • , Christian Behrends
    • , Jerome Gilleron
    • , Stephan Herzig
    •  & Anja Zeigerer
  • Article |

    Anoxia─lack of oxygen─commonly occurs during ischaemic heart disease. Using yeast, worms and mice, Hannich et al. show that anoxia-associated tissue injury and cell death are due to accumulation of a non-canonical sphingolipid, 1-deoxydihydroceramide, that damages the cytoskeleton.

    • J. Thomas Hannich
    • , A. Galih Haribowo
    • , Sébastien Gentina
    • , Melanie Paillard
    • , Ludovic Gomez
    • , Bruno Pillot
    • , Hélène Thibault
    • , Daniel Abegg
    • , Nicolas Guex
    • , Andreas Zumbuehl
    • , Alexander Adibekian
    • , Michel Ovize
    • , Jean-Claude Martinou
    •  & Howard Riezman
  • Article |

    After development, adult skeletal muscle retains the capacity to regenerate by activating muscle stem cells. Here the authors demonstrate that the glycosylphosphatidylinositol-anchored membrane protein GAS1, which is induced in muscle stem cells with age, suppresses muscle regenerative capacity but can be inhibited by glial cell line-derived neurotrophic factor (GDNF).

    • Liangji Li
    • , Michelle Rozo
    • , Sibiao Yue
    • , Xiaobin Zheng
    • , Frederick J. Tan
    • , Christoph Lepper
    •  & Chen-Ming Fan
  • Article |

    The liver is a heterogeneous organ organized in lobules that are radially polarized. The use of single-cell spatial transcriptomics has revealed that half of hepatic genes are differentially expressed across the lobule. Ben-Moshe et al. show how a multi-omics approach, which consists of transcriptomics, micro RNA profiling and proteomics, allows for characterization of liver heterogeneity with higher resolution.

    • Shani Ben-Moshe
    • , Yonatan Shapira
    • , Andreas E. Moor
    • , Rita Manco
    • , Tamar Veg
    • , Keren Bahar Halpern
    •  & Shalev Itzkovitz
  • Article |

    Tajima and colleagues identify mitochondrial lipoylation as a post-transcriptional molecular signature of aged brown adipose tissue (BAT) in mice. Reduced mitochondrial lipoylation is tightly coupled with the age-associated decline in BAT function, whereas enhanced lipoylation restores BAT activity in aged mice.

    • Kazuki Tajima
    • , Kenji Ikeda
    • , Hsin-Yi Chang
    • , Chih-Hsiang Chang
    • , Takeshi Yoneshiro
    • , Yasuo Oguri
    • , Heejin Jun
    • , Jun Wu
    • , Yasushi Ishihama
    •  & Shingo Kajimura
  • Article |

    Chen et al. report that TGF-β signalling, although largely considered anti-inflammatory, has proinflammatory effects on endothelial cells. Inhibition of endothelial TGF-β signalling decreases atherosclerosis in mice and reverts established plaques, in part by decreasing endothelial-to-mesenchymal transitions.

    • Pei-Yu Chen
    • , Lingfeng Qin
    • , Guangxin Li
    • , Zheng Wang
    • , James E. Dahlman
    • , Jose Malagon-Lopez
    • , Sharvari Gujja
    • , Nicholas A. Cilfone
    • , Kevin J. Kauffman
    • , Lele Sun
    • , Hongye Sun
    • , Xinbo Zhang
    • , Binod Aryal
    • , Alberto Canfran-Duque
    • , Rebecca Liu
    • , Pascal Kusters
    • , Alfica Sehgal
    • , Yang Jiao
    • , Daniel G. Anderson
    • , Jeffrey Gulcher
    • , Carlos Fernandez-Hernando
    • , Esther Lutgens
    • , Martin A. Schwartz
    • , Jordan S. Pober
    • , Thomas W. Chittenden
    • , George Tellides
    •  & Michael Simons
  • Article |

    Some follicular B cell lymphomas harbour activating mutations in RRAGC, activator of the nutrient sensor mTORC1. Here the authors show that these mutations confer insensitivity to nutrient deprivation and synergize with paracrine cues from the supportive T cell microenvironment to accelerate lymphomagenesis, but impose vulnerability to inhibition of mTORC1.

    • Ana Ortega-Molina
    • , Nerea Deleyto-Seldas
    • , Joaquim Carreras
    • , Alba Sanz
    • , Cristina Lebrero-Fernández
    • , Camino Menéndez
    • , Andrew Vandenberg
    • , Beatriz Fernández-Ruiz
    • , Leyre Marín-Arraiza
    • , Celia de la Calle Arregui
    • , Ana Belén Plata-Gómez
    • , Eduardo Caleiras
    • , Alba de Martino
    • , Nuria Martínez-Martín
    • , Kevin Troulé
    • , Elena Piñeiro-Yáñez
    • , Naoya Nakamura
    • , Shamzah Araf
    • , Gabriel D. Victora
    • , Jessica Okosun
    • , Jude Fitzgibbon
    •  & Alejo Efeyan
  • Article |

    Folgueira et al. show that dopamine signalling in the lateral hypothalamic area and the zona incerta reduces body weight and increases energy expenditure by increasing brown adipose tissue thermogenesis in rodents. Weight loss and increased energy expenditure were also observed in patients treated with a dopamine receptor 2 agonist.

    • Cintia Folgueira
    • , Daniel Beiroa
    • , Begoña Porteiro
    • , Manon Duquenne
    • , Emma Puighermanal
    • , Marcos F. Fondevila
    • , Silvia Barja-Fernández
    • , Rosalia Gallego
    • , René Hernández-Bautista
    • , Cecilia Castelao
    • , Ana Senra
    • , Patricia Seoane-Collazo
    • , Noemi Gómez-Lado
    • , Pablo Aguiar
    • , Diana Guallar
    • , Miguel Fidalgo
    • , Amparo Romero-Pico
    • , Roger Adan
    • , Clemence Blouet
    • , Jose Luís Labandeira-García
    • , Françoise Jeanrenaud
    • , Imre Kallo
    • , Zsolt Liposits
    • , Javier Salvador
    • , Vincent Prevot
    • , Carlos Dieguez
    • , Miguel López
    • , Emmanuel Valjent
    • , Gema Frühbeck
    • , Luisa M. Seoane
    •  & Ruben Nogueiras
  • Article |

    Brown adipose tissue (BAT) has high thermogenic potential and is considered a promising target to counteract obesity. Here de Jong et al. demonstrate that human BAT is more similar to classical brown than to beige adipose tissue from mice kept at thermoneutrality and challenged with a high-fat diet.

    • Jasper M. A. de Jong
    • , Wenfei Sun
    • , Nuno D. Pires
    • , Andrea Frontini
    • , Miroslav Balaz
    • , Naja Z. Jespersen
    • , Amir Feizi
    • , Katarina Petrovic
    • , Alexander W. Fischer
    • , Muhammad Hamza Bokhari
    • , Tarja Niemi
    • , Pirjo Nuutila
    • , Saverio Cinti
    • , Søren Nielsen
    • , Camilla Scheele
    • , Kirsi Virtanen
    • , Barbara Cannon
    • , Jan Nedergaard
    • , Christian Wolfrum
    •  & Natasa Petrovic
  • Article |

    Although germline removal normally extends Caenorhabditis elegans lifespan, Lee et al. show that low temperature does not extend lifespan in germline-lacking mutant worms. Cold temperatures (10 °C, 15 °C) delay germline stem cell exhaustion, releasing prostaglandin E2 hormone, which induces cbs-1 in the intestine to produce hydrogen sulfide and prolong lifespan.

    • Hyun Ju Lee
    • , Alireza Noormohammadi
    • , Seda Koyuncu
    • , Giuseppe Calculli
    • , Milos S. Simic
    • , Marija Herholz
    • , Aleksandra Trifunovic
    •  & David Vilchez
  • Article |

    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.

    • Gretchen L. Seim
    • , Emily C. Britt
    • , Steven V. John
    • , Franklin J. Yeo
    • , Aaron R. Johnson
    • , Richard S. Eisenstein
    • , David J. Pagliarini
    •  & Jing Fan
  • Article |

    Spontaneous control of HIV is linked to the ability of CD8+ T cells to eliminate infected CD4+ T cells. Here, the authors uncover metabolic differences between HIV-specific, central memory CD8+ T cells from spontaneous HIV controllers and antiretrovirally treated non-controllers, and show that in vitro metabolic reprogramming enhances the antiviral response in non-controllers cells.

    • Mathieu Angin
    • , Stevenn Volant
    • , Caroline Passaes
    • , Camille Lecuroux
    • , Valérie Monceaux
    • , Marie-Agnès Dillies
    • , José Carlos Valle-Casuso
    • , Gianfranco Pancino
    • , Bruno Vaslin
    • , Roger Le Grand
    • , Laurence Weiss
    • , Cecile Goujard
    • , Laurence Meyer
    • , Faroudy Boufassa
    • , Michaela Müller-Trutwin
    • , Olivier Lambotte
    •  & Asier Sáez-Cirión
  • Article |

    Increased metabolic activity promotes HIV-1 infection in CD4 T lymphocytes, but the contribution of different metabolic pathways is unclear. Here the authors show that carbon entry into the citric acid cycle is required to support the early stages of HIV-1 infection.

    • Isabelle Clerc
    • , Daouda Abba Moussa
    • , Zoi Vahlas
    • , Saverio Tardito
    • , Leal Oburoglu
    • , Thomas J. Hope
    • , Marc Sitbon
    • , Valérie Dardalhon
    • , Cédric Mongellaz
    •  & Naomi Taylor
  • Article |

    Non-coding RNAs are important regulators of several biological processes, including metabolic functions. Here Arcinas and colleagues demonstrate that circular RNAs, a class of non-coding RNAs, are widely expressed in adipose tissue and display dynamic regulation during adipogenesis and obesity.

    • Camille Arcinas
    • , Wilson Tan
    • , Wenning Fang
    • , Tresha P. Desai
    • , Diana Chee Siang Teh
    • , Ufuk Degirmenci
    • , Dan Xu
    • , Roger Foo
    •  & Lei Sun
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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