Endocrinology

  • Article
    | Open Access

    miRNA142-3p and Tet2 are separately known to regulate Treg. Here the authors show that miRNA142-3p targets Tet2 and by this opposes Treg differentiation in autoimmune diabetes.

    • Martin G. Scherm
    • , Isabelle Serr
    • , Adam M. Zahm
    • , Jonathan Schug
    • , Saverio Bellusci
    • , Rossella Manfredini
    • , Victoria K. Salb
    • , Katharina Gerlach
    • , Benno Weigmann
    • , Anette-Gabriele Ziegler
    • , Klaus H. Kaestner
    •  & Carolin Daniel
  • Article
    | Open Access

    Primary cilia have been proposed to regulate glucose metabolism and insulin secretion in beta cells, but it is not known how. Here the authors show that primary cilia play a role in adult β-cell function via a mechanism involving endosomal EphA-processing.

    • Francesco Volta
    • , M. Julia Scerbo
    • , Anett Seelig
    • , Robert Wagner
    • , Nils O’Brien
    • , Felicia Gerst
    • , Andreas Fritsche
    • , Hans-Ulrich Häring
    • , Anja Zeigerer
    • , Susanne Ullrich
    •  & Jantje M. Gerdes
  • Article
    | Open Access

    Gut microbiota alterations, including enrichment of flagellated bacteria, are associated with metabolic syndrome and chronic inflammatory diseases. Here, Tran et al. show, in mice, that elicitation of mucosal anti-flagellin antibodies protects against experimental colitis and ameliorates diet-induced obesity.

    • Hao Q. Tran
    • , Ruth E. Ley
    • , Andrew T. Gewirtz
    •  & Benoit Chassaing
  • Article
    | Open Access

    The adipokine leptin modulates intestinal inflammation in mice. Here the authors describe a patient with inflammatory bowel disease and lipodystrophy, providing evidence that leptin aggravates intestinal inflammation with proinflammatory effects on leukocytes that are reversible by TNFα blockade.

    • Jörn F. Ziegler
    • , Chotima Böttcher
    • , Marilena Letizia
    • , Cansu Yerinde
    • , Hao Wu
    • , Inka Freise
    • , Yasmina Rodriguez-Sillke
    • , Ani K. Stoyanova
    • , Martin E. Kreis
    • , Patrick Asbach
    • , Desiree Kunkel
    • , Josef Priller
    • , Ioannis Anagnostopoulos
    • , Anja A. Kühl
    • , Konstanze Miehle
    • , Michael Stumvoll
    • , Florian Tran
    • , Broder Fredrich
    • , Michael Forster
    • , Andre Franke
    • , Christian Bojarski
    • , Rainer Glauben
    • , Britt-Sabina Löscher
    • , Britta Siegmund
    •  & Carl Weidinger
  • Article
    | Open Access

    The invasion of epithelial tumours often depends on the epithelial-mesenchymal transition. Here, the authors report that intracellular activation of thyroid hormone by the D2 deiodinase enzyme promotes invasion and progression of squamous cell carcinoma by transcriptionally up-regulating ZEB-1.

    • Caterina Miro
    • , Emery Di Cicco
    • , Raffaele Ambrosio
    • , Giuseppina Mancino
    • , Daniela Di Girolamo
    • , Annunziata Gaetana Cicatiello
    • , Serena Sagliocchi
    • , Annarita Nappi
    • , Maria Angela De Stefano
    • , Cristina Luongo
    • , Dario Antonini
    • , Feliciano Visconte
    • , Silvia Varricchio
    • , Gennaro Ilardi
    • , Luigi Del Vecchio
    • , Stefania Staibano
    • , Anita Boelen
    • , Cedric Blanpain
    • , Caterina Missero
    • , Domenico Salvatore
    •  & Monica Dentice
  • Article
    | Open Access

    Histone deacetylase 3 (HDAC3) is a regulator of lipid homeostasis in several tissues, however, its role in intestinal lipid metabolism was not yet known. Here the authors study intestine specific HDAC3 knock out mice and report that these animals have increased fatty acid oxidation and undergo remodeling of the intestinal epithelial cell lipidome.

    • Mercedes Dávalos-Salas
    • , Magdalene K. Montgomery
    • , Camilla M. Reehorst
    • , Rebecca Nightingale
    • , Irvin Ng
    • , Holly Anderton
    • , Sheren Al-Obaidi
    • , Analia Lesmana
    • , Cameron M. Scott
    • , Paul Ioannidis
    • , Hina Kalra
    • , Shivakumar Keerthikumar
    • , Lars Tögel
    • , Angela Rigopoulos
    • , Sylvia J. Gong
    • , David S. Williams
    • , Prusoth Yoganantharaja
    • , Kim Bell-Anderson
    • , Suresh Mathivanan
    • , Yann Gibert
    • , Scott Hiebert
    • , Andrew M. Scott
    • , Matthew J. Watt
    •  & John M. Mariadason
  • Article
    | Open Access

    The molecular mechanisms of mitochondrial dysfunction in the premature ageing Werner syndrome were elusive. Here the authors show that NAD+ depletion-induced impaired mitophagy contributes to this phenomenon, shedding light on potential therapeutics.

    • Evandro F. Fang
    • , Yujun Hou
    • , Sofie Lautrup
    • , Martin Borch Jensen
    • , Beimeng Yang
    • , Tanima SenGupta
    • , Domenica Caponio
    • , Rojyar Khezri
    • , Tyler G. Demarest
    • , Yahyah Aman
    • , David Figueroa
    • , Marya Morevati
    • , Ho-Joon Lee
    • , Hisaya Kato
    • , Henok Kassahun
    • , Jong-Hyuk Lee
    • , Deborah Filippelli
    • , Mustafa Nazir Okur
    • , Aswin Mangerich
    • , Deborah L. Croteau
    • , Yoshiro Maezawa
    • , Costas A. Lyssiotis
    • , Jun Tao
    • , Koutaro Yokote
    • , Tor Erik Rusten
    • , Mark P. Mattson
    • , Heinrich Jasper
    • , Hilde Nilsen
    •  & Vilhelm A. Bohr
  • Article
    | Open Access

    Cellular overgrowth and fibrosis in the foreign body response can compromise the function of transplanted cells. Here, the authors report on the zwitterionically modified alginates for the encapsulation of cells to reduce cellular overgrowth and demonstrate application in mice, dogs and pigs.

    • Qingsheng Liu
    • , Alan Chiu
    • , Long-Hai Wang
    • , Duo An
    • , Monica Zhong
    • , Alexandra M. Smink
    • , Bart J. de Haan
    • , Paul de Vos
    • , Kevin Keane
    • , Andreas Vegge
    • , Esther Y. Chen
    • , Wei Song
    • , Wendy F. Liu
    • , James Flanders
    • , Claude Rescan
    • , Lars Groth Grunnet
    • , Xi Wang
    •  & Minglin Ma
  • Article
    | Open Access

    Mutations in the chloride channel ClC-2 have been associated with familial forms of hyperaldosteronism. Here, Schewe et al. generated a mouse model carrying the most common mutation found in patients and find it recapitulates key features of the disease, providing a unique tool for future studies on its pathogenesis.

    • Julia Schewe
    • , Eric Seidel
    • , Sofia Forslund
    • , Lajos Marko
    • , Jörg Peters
    • , Dominik N. Muller
    • , Christoph Fahlke
    • , Gabriel Stölting
    •  & Ute Scholl
  • Article
    | Open Access

    Sleep duration is associated with an adverse lipid profile. Here, the authors perform genome-wide gene-by-sleep interaction analysis and find 49 previously unreported lipid loci when considering short or long total sleep time.

    • Raymond Noordam
    • , Maxime M. Bos
    • , Heming Wang
    • , Thomas W. Winkler
    • , Amy R. Bentley
    • , Tuomas O. Kilpeläinen
    • , Paul S. de Vries
    • , Yun Ju Sung
    • , Karen Schwander
    • , Brian E. Cade
    • , Alisa Manning
    • , Hugues Aschard
    • , Michael R. Brown
    • , Han Chen
    • , Nora Franceschini
    • , Solomon K. Musani
    • , Melissa Richard
    • , Dina Vojinovic
    • , Stella Aslibekyan
    • , Traci M. Bartz
    • , Lisa de las Fuentes
    • , Mary Feitosa
    • , Andrea R. Horimoto
    • , Marjan Ilkov
    • , Minjung Kho
    • , Aldi Kraja
    • , Changwei Li
    • , Elise Lim
    • , Yongmei Liu
    • , Dennis O. Mook-Kanamori
    • , Tuomo Rankinen
    • , Salman M. Tajuddin
    • , Ashley van der Spek
    • , Zhe Wang
    • , Jonathan Marten
    • , Vincent Laville
    • , Maris Alver
    • , Evangelos Evangelou
    • , Maria E. Graff
    • , Meian He
    • , Brigitte Kühnel
    • , Leo-Pekka Lyytikäinen
    • , Pedro Marques-Vidal
    • , Ilja M. Nolte
    • , Nicholette D. Palmer
    • , Rainer Rauramaa
    • , Xiao-Ou Shu
    • , Harold Snieder
    • , Stefan Weiss
    • , Wanqing Wen
    • , Lisa R. Yanek
    • , Correa Adolfo
    • , Christie Ballantyne
    • , Larry Bielak
    • , Nienke R. Biermasz
    • , Eric Boerwinkle
    • , Niki Dimou
    • , Gudny Eiriksdottir
    • , Chuan Gao
    • , Sina A. Gharib
    • , Daniel J. Gottlieb
    • , José Haba-Rubio
    • , Tamara B. Harris
    • , Sami Heikkinen
    • , Raphaël Heinzer
    • , James E. Hixson
    • , Georg Homuth
    • , M. Arfan Ikram
    • , Pirjo Komulainen
    • , Jose E. Krieger
    • , Jiwon Lee
    • , Jingmin Liu
    • , Kurt K. Lohman
    • , Annemarie I. Luik
    • , Reedik Mägi
    • , Lisa W. Martin
    • , Thomas Meitinger
    • , Andres Metspalu
    • , Yuri Milaneschi
    • , Mike A. Nalls
    • , Jeff O’Connell
    • , Annette Peters
    • , Patricia Peyser
    • , Olli T. Raitakari
    • , Alex P. Reiner
    • , Patrick C. N. Rensen
    • , Treva K. Rice
    • , Stephen S. Rich
    • , Till Roenneberg
    • , Jerome I. Rotter
    • , Pamela J. Schreiner
    • , James Shikany
    • , Stephen S. Sidney
    • , Mario Sims
    • , Colleen M. Sitlani
    • , Tamar Sofer
    • , Konstantin Strauch
    • , Morris A. Swertz
    • , Kent D. Taylor
    • , André G. Uitterlinden
    • , Cornelia M. van Duijn
    • , Henry Völzke
    • , Melanie Waldenberger
    • , Robert B. Wallance
    • , Ko Willems van Dijk
    • , Caizheng Yu
    • , Alan B. Zonderman
    • , Diane M. Becker
    • , Paul Elliott
    • , Tõnu Esko
    • , Christian Gieger
    • , Hans J. Grabe
    • , Timo A. Lakka
    • , Terho Lehtimäki
    • , Kari E. North
    • , Brenda W. J. H. Penninx
    • , Peter Vollenweider
    • , Lynne E. Wagenknecht
    • , Tangchun Wu
    • , Yong-Bing Xiang
    • , Wei Zheng
    • , Donna K. Arnett
    • , Claude Bouchard
    • , Michele K. Evans
    • , Vilmundur Gudnason
    • , Sharon Kardia
    • , Tanika N. Kelly
    • , Stephen B. Kritchevsky
    • , Ruth J. F. Loos
    • , Alexandre C. Pereira
    • , Mike Province
    • , Bruce M. Psaty
    • , Charles Rotimi
    • , Xiaofeng Zhu
    • , Najaf Amin
    • , L. Adrienne Cupples
    • , Myriam Fornage
    • , Ervin F. Fox
    • , Xiuqing Guo
    • , W. James Gauderman
    • , Kenneth Rice
    • , Charles Kooperberg
    • , Patricia B. Munroe
    • , Ching-Ti Liu
    • , Alanna C. Morrison
    • , Dabeeru C. Rao
    • , Diana van Heemst
    •  & Susan Redline
  • Article
    | Open Access

    Type 1 as well as type 2 diabetes are characterized by a loss of insulin-producing β-cells. Here the authors show that the FDA-approved drug neratinib has beneficial effects on β-cell survival, insulin secretion, and glycemic control in mouse models of diabetes.

    • Amin Ardestani
    • , Sijia Li
    • , Karthika Annamalai
    • , Blaz Lupse
    • , Shirin Geravandi
    • , Aleksandra Dobrowolski
    • , Shan Yu
    • , Siying Zhu
    • , Tyler D. Baguley
    • , Murali Surakattula
    • , Janina Oetjen
    • , Lena Hauberg-Lotte
    • , Raquel Herranz
    • , Sushil Awal
    • , Delsi Altenhofen
    • , Van Nguyen-Tran
    • , Sean Joseph
    • , Peter G. Schultz
    • , Arnab K. Chatterjee
    • , Nikki Rogers
    • , Matthew S. Tremblay
    • , Weijun Shen
    •  & Kathrin Maedler
  • Article
    | Open Access

    Impulsive behaviour is common in various neuropsychiatric disorders. Here, the authors identify a pathway from the lateral hypothalamus to the ventral hippocampus and the role of melanin-concentrating hormone signaling in these neurons in specifically regulating impulsivity.

    • Emily E. Noble
    • , Zhuo Wang
    • , Clarissa M. Liu
    • , Elizabeth A. Davis
    • , Andrea N. Suarez
    • , Lauren M. Stein
    • , Linda Tsan
    • , Sarah J. Terrill
    • , Ted M. Hsu
    • , A-Hyun Jung
    • , Lauren M. Raycraft
    • , Joel D. Hahn
    • , Martin Darvas
    • , Alyssa M. Cortella
    • , Lindsey A. Schier
    • , Alexander W. Johnson
    • , Matthew R. Hayes
    • , Daniel P. Holschneider
    •  & Scott E. Kanoski
  • Article
    | Open Access

    It’s well known that hippocampal synaptic plasticity and memory are impaired in experimental models of metabolic diseases, however, it is unclear if maternal diet or metabolic alterations around the gestational age may multigenerationally affect learning and memory. In this study, authors demonstrate that maternal high fat diet-dependent insulin resistance affects synaptic plasticity and memory of descendants until the third generation via reduced exon specific brain-derived neurotrophic factor expression in the hippocampus of descendants

    • Salvatore Fusco
    • , Matteo Spinelli
    • , Sara Cocco
    • , Cristian Ripoli
    • , Alessia Mastrodonato
    • , Francesca Natale
    • , Marco Rinaudo
    • , Giulia Livrizzi
    •  & Claudio Grassi
  • Article
    | Open Access

    Elevated inorganic phosphate levels promote excessive parathyroid hormone secretion, which contributes to the aetiology of secondary hyperparathyroidism. Here, the authors show that phosphate directly inhibits the calcium-sensing receptor, the main regulator of parathyroid hormone secretion.

    • Patricia P. Centeno
    • , Amanda Herberger
    • , Hee-Chang Mun
    • , Chialing Tu
    • , Edward F. Nemeth
    • , Wenhan Chang
    • , Arthur D. Conigrave
    •  & Donald T. Ward
  • Article
    | Open Access

    Mutations in the chloride channel ClC-2 have been found in primary aldosteronism (PA). Here, Göppner et al. generate transgenic mice expressing a mutant form of ClC-2 that displays increased chloride currents like patient mutations, and find it recapitulates the key pathological features of PA.

    • Corinna Göppner
    • , Ian J. Orozco
    • , Maja B. Hoegg-Beiler
    • , Audrey H. Soria
    • , Christian A. Hübner
    • , Fabio L. Fernandes-Rosa
    • , Sheerazed Boulkroun
    • , Maria-Christina Zennaro
    •  & Thomas J. Jentsch
  • Article
    | Open Access

    The success of engineered tissue depends on the integration of a dense vascular network to supply nutrients and remove waste products. Here the authors design high density microvascular meshes made through an anchored self-assembly mechanism, and use these meshes to support subcutaneous pancreatic islet survival in a mouse diabetes model.

    • Wei Song
    • , Alan Chiu
    • , Long-Hai Wang
    • , Robert E. Schwartz
    • , Bin Li
    • , Nikolaos Bouklas
    • , Daniel T. Bowers
    • , Duo An
    • , Soon Hon Cheong
    • , James A. Flanders
    • , Yehudah Pardo
    • , Qingsheng Liu
    • , Xi Wang
    • , Vivian K. Lee
    • , Guohao Dai
    •  & Minglin Ma
  • Article
    | Open Access

    Nicotinamide adenine dinucleotide (NAD+) sustains cellular energy metabolism, functions as a substrate of Sirt and PARP enzymes, and its supplementation is explored therapeutically in aging and other contexts. Here the authors provide insight into the role of endogenous NAD+ metabolism by studying nicotinamide riboside kinase 1 (NRK1) deficient mice.

    • Audrey Sambeat
    • , Joanna Ratajczak
    • , Magali Joffraud
    • , José L. Sanchez-Garcia
    • , Maria P. Giner
    • , Armand Valsesia
    • , Judith Giroud-Gerbetant
    • , Miriam Valera-Alberni
    • , Angelique Cercillieux
    • , Marie Boutant
    • , Sameer S. Kulkarni
    • , Sofia Moco
    •  & Carles Canto
  • Article
    | Open Access

    Surgical weight-loss interventions improve insulin sensitivity via incompletely understood mechanisms. Here the authors assess skeletal muscle epigenetic changes in individuals with obesity following metabolic surgery and compare them with data from individuals without obesity.

    • Sofiya Gancheva
    • , Meriem Ouni
    • , Tomas Jelenik
    • , Chrysi Koliaki
    • , Julia Szendroedi
    • , Frederico G. S. Toledo
    • , Daniel F. Markgraf
    • , Dominik H. Pesta
    • , Lucia Mastrototaro
    • , Elisabetta De Filippo
    • , Christian Herder
    • , Markus Jähnert
    • , Jürgen Weiss
    • , Klaus Strassburger
    • , Matthias Schlensak
    • , Annette Schürmann
    •  & Michael Roden
  • Article
    | Open Access

    The relationship between metabolomic and behavioral changes is not well understood. Here, the authors analyze metabolome changes in D. melanogaster heads and bodies during hunger and satiety, and develop the Flyscape tool to visualize the resulting metabolic networks and integrate them with other omics data.

    • Daniel Wilinski
    • , Jasmine Winzeler
    • , William Duren
    • , Jenna L. Persons
    • , Kristina J. Holme
    • , Johan Mosquera
    • , Morteza Khabiri
    • , Jason M. Kinchen
    • , Peter L. Freddolino
    • , Alla Karnovsky
    •  & Monica Dus
  • Article
    | Open Access

    While many pleiotropic genetic loci have been identified, how they contribute to phenotypes across traits and diseases is unclear. Here, the authors propose decomposition of genetic associations (DeGAs), which uses singular value decomposition, to characterize the underlying latent structure of genetic associations of 2,138 phenotypes.

    • Yosuke Tanigawa
    • , Jiehan Li
    • , Johanne M. Justesen
    • , Heiko Horn
    • , Matthew Aguirre
    • , Christopher DeBoever
    • , Chris Chang
    • , Balasubramanian Narasimhan
    • , Kasper Lage
    • , Trevor Hastie
    • , Chong Y. Park
    • , Gill Bejerano
    • , Erik Ingelsson
    •  & Manuel A. Rivas
  • Article
    | Open Access

    IL-36α,β and ɣ are IL-1-related cytokines promoting inflammation in the skin and intestine. Here the authors show they are elevated in individuals with obesity, and that mice lacking the IL-36 receptor antagonist are more resistant to diet-induced obesity and metabolic dysfunction, which depends on intestinal microbiota.

    • Eirini Giannoudaki
    • , Yasmina E. Hernandez-Santana
    • , Kelly Mulfaul
    • , Sarah L. Doyle
    • , Emily Hams
    • , Padraic G. Fallon
    • , Arimin Mat
    • , Donal O’Shea
    • , Manfred Kopf
    • , Andrew E. Hogan
    •  & Patrick T. Walsh
  • Article
    | Open Access

    Pancreatic islets are composed of alpha-, beta-, as well as delta-cells and appropriate regulation of glucose homeostasis relies on auto- and paracrine cellular communication. Here, the authors study the role of delta-cell filopodia in this context by employing optogenetic and calcium imaging approaches.

    • Rafael Arrojo e Drigo
    • , Stefan Jacob
    • , Concha F. García-Prieto
    • , Xiaofeng Zheng
    • , Masahiro Fukuda
    • , Hoa Tran Thi Nhu
    • , Olga Stelmashenko
    • , Flavia Letícia Martins Peçanha
    • , Rayner Rodriguez-Diaz
    • , Eric Bushong
    • , Thomas Deerinck
    • , Sebastien Phan
    • , Yusuf Ali
    • , Ingo Leibiger
    • , Minni Chua
    • , Thomas Boudier
    • , Sang-Ho Song
    • , Martin Graf
    • , George J. Augustine
    • , Mark H. Ellisman
    •  & Per-Olof Berggren
  • Article
    | Open Access

    The effect of diet-induced obesity on intestinal B cell populations is not well understood despite emerging evidence of a critical role for the intestinal immune system in contributing to insulin resistance. Here, the authors show important functions of IgA in regulating metabolic disease and for intestinal immunity in modulating systemic glucose metabolism.

    • Helen Luck
    • , Saad Khan
    • , Justin H. Kim
    • , Julia K. Copeland
    • , Xavier S. Revelo
    • , Sue Tsai
    • , Mainak Chakraborty
    • , Kathleen Cheng
    • , Yi Tao Chan
    • , Mark K. Nøhr
    • , Xavier Clemente-Casares
    • , Marie-Christine Perry
    • , Magar Ghazarian
    • , Helena Lei
    • , Yi-Hsuan Lin
    • , Bryan Coburn
    • , Allan Okrainec
    • , Timothy Jackson
    • , Susan Poutanen
    • , Herbert Gaisano
    • , Johane P. Allard
    • , David S. Guttman
    • , Margaret E. Conner
    • , Shawn Winer
    •  & Daniel A. Winer
  • Article
    | Open Access

    Insulin replacement is a valuable therapy for insulin deficiency, however, other therapies are being investigated to restore metabolic homeostasis. Here, the authors identify S100A9 as a leptin induced circulating cue that improves glucose and lipid homeostasis and extends survival in insulin deficient mice.

    • Giorgio Ramadori
    • , Sanda Ljubicic
    • , Serena Ricci
    • , Despoina Mikropoulou
    • , Xavier Brenachot
    • , Christelle Veyrat-Durebex
    • , Ebru Aras
    • , Rafael M. Ioris
    • , Jordi Altirriba
    • , Elisabeth Malle
    • , Dirk Foell
    • , Thomas Vogl
    •  & Roberto Coppari
  • Article
    | Open Access

    The circadian clock regulates rhythms of behavior and physiology and the timing of circadian rhythms in liver is influenced by food intake. Here, the authors identify the hepatokine Angptl8 as a mediator of liver clock food entrainment.

    • Siyu Chen
    • , Mengyang Feng
    • , Shiyao Zhang
    • , Zhewen Dong
    • , Yifan Wang
    • , Wenxiang Zhang
    •  & Chang Liu
  • Article
    | Open Access

    Diabetes is associated with decreased PI3K activation in skeletal muscle. Here, the authors show that p110a is the predominant PI3K subunit in muscle, and show that its ablation in muscle, but not ablation of p110beta, leads to insulin resistance, increased proteosomal and autophagic activity, and altered mitochondria homeostasis in mice.

    • Mengyao Ella Li
    • , Hans P. M. M. Lauritzen
    • , Brian T. O’Neill
    • , Chih-Hao Wang
    • , Weikang Cai
    • , Bruna B. Brandao
    • , Masaji Sakaguchi
    • , Rongya Tao
    • , Michael F. Hirshman
    • , Samir Softic
    •  & C. Ronald Kahn
  • Article
    | Open Access

    Impaired beta-cell insulin secretion is a key pathological feature of type 2 diabetes. Here, the authors describe metabolic stress induced lysosomal degradation of newly formed insulin granules, independent of macroautophagy, as a potential mechanism for beta-cell dysfunction.

    • Adrien Pasquier
    • , Kevin Vivot
    • , Eric Erbs
    • , Coralie Spiegelhalter
    • , Zhirong Zhang
    • , Victor Aubert
    • , Zengzhen Liu
    • , Meryem Senkara
    • , Elisa Maillard
    • , Michel Pinget
    • , Julie Kerr-Conte
    • , François Pattou
    • , Gilbert Marciniak
    • , Axel Ganzhorn
    • , Paolo Ronchi
    • , Nicole L. Schieber
    • , Yannick Schwab
    • , Paul Saftig
    • , Alexander Goginashvili
    •  & Romeo Ricci
  • Article
    | Open Access

    Whether adipose ILC1s regulate adipose tissue fibrogenesis is unknown. Here, the authors report a direct role of adipose ILC1s in adipose tissue fibrogenesis and provide insights into the mechanisms of local immune dysfunction in obesity-associated metabolic disorders.

    • Hongdong Wang
    • , Lei Shen
    • , Xitai Sun
    • , Fangcen Liu
    • , Wenhuan Feng
    • , Chunping Jiang
    • , Xuehui Chu
    • , Xiao Ye
    • , Can Jiang
    • , Yan Wang
    • , Pengzi Zhang
    • , Mengwei Zang
    • , Dalong Zhu
    •  & Yan Bi
  • Article
    | Open Access

    Type 2 diabetes (T2D) is prevalent in populations worldwide, however, mostly studied in European and mixed-ancestry populations. Here, the authors perform a genome-wide association study for T2D in over 5,000 sub-Saharan Africans and identify a locus, ZRANB3, that is specific for this population.

    • Adebowale A. Adeyemo
    • , Norann A. Zaghloul
    • , Guanjie Chen
    • , Ayo P. Doumatey
    • , Carmen C. Leitch
    • , Timothy L. Hostelley
    • , Jessica E. Nesmith
    • , Jie Zhou
    • , Amy R. Bentley
    • , Daniel Shriner
    • , Olufemi Fasanmade
    • , Godfrey Okafor
    • , Benjamin Eghan Jr
    • , Kofi Agyenim-Boateng
    • , Settara Chandrasekharappa
    • , Jokotade Adeleye
    • , William Balogun
    • , Samuel Owusu
    • , Albert Amoah
    • , Joseph Acheampong
    • , Thomas Johnson
    • , Johnnie Oli
    • , Clement Adebamowo
    • , Ji Chen
    • , Meng Sun
    • , Fraser Pirie
    • , Tommy Carstensen
    • , Cristina Pomilla
    • , Elizabeth H. Young
    • , Manjinder Sandhu
    • , Andrew P. Morris
    • , Inês Barroso
    • , Mark I. McCarthy
    • , Anubha Mahajan
    • , Eleanor Wheeler
    • , Ayesha A. Motala
    • , Francis Collins
    • , Georgia Dunston
    •  & Charles N. Rotimi
  • Article
    | Open Access

    Defective CFTR protein, responsible for Cystic Fibrosis (CF), is highly expressed in pancreatic ductal epithelial cells (PDECs) but their impact on insulin secreting pancreatic islets is not fully understood. Here the authors develop a non-CF and CF patient derived pancreas-on-a-chip model to study how CF affects insulin secretion.

    • Kyu Shik Mun
    • , Kavisha Arora
    • , Yunjie Huang
    • , Fanmuyi Yang
    • , Sunitha Yarlagadda
    • , Yashaswini Ramananda
    • , Maisam Abu-El-Haija
    • , Joseph J. Palermo
    • , Balamurugan N. Appakalai
    • , Jaimie D. Nathan
    •  & Anjaparavanda P. Naren
  • Article
    | Open Access

    The adaptor protein SHN3 suppresses new bone formation by controlling osteoblast activity. Here, the authors show that ablation of SHN3 function, either genetically or by delivering an artificial miRNA via AAV9, rescues bone loss in osteoporotic mice, and show that engineering of the AAV9 capsid improves targeting to bone

    • Yeon-Suk Yang
    • , Jun Xie
    • , Dan Wang
    • , Jung-Min Kim
    • , Phillip W. L. Tai
    • , Ellen Gravallese
    • , Guangping Gao
    •  & Jae-Hyuck Shim
  • Article
    | Open Access

    Beta3-adrenergic receptor signaling regulates adipose tissue browning. Here, the authors show that barr2 regulates internalization of beta3-adrenergic receptors and that mice lacking barr2 in adipocytes are protected from diet-induced weight gain and metabolic complications.

    • Sai P. Pydi
    • , Shanu Jain
    • , Wesley Tung
    • , Yinghong Cui
    • , Lu Zhu
    • , Wataru Sakamoto
    • , Shalini Jain
    • , Brent S. Abel
    • , Monica C. Skarulis
    • , Jie Liu
    • , Thanh Huynh
    • , Karel Pacak
    • , Marc G. Caron
    • , Oksana Gavrilova
    • , Toren Finkel
    •  & Jürgen Wess
  • Article
    | Open Access

    Increased inflammation during ageing promotes osteoporosis by activating osteoclast function and inhibiting osteoblasts. Here, the authors show that TGFβ1 release from bone matrix during ageing induces degradation of TRAF3 in mesenchymal progenitor cells, leading to reduced osteoblast differentiation and increased osteoclast formation, and suggesting that pharmacological stabilization of TRAF3 could ameliorate age-related osteoporosis.

    • Jinbo Li
    • , Akram Ayoub
    • , Yan Xiu
    • , Xiaoxiang Yin
    • , James O. Sanders
    • , Addisu Mesfin
    • , Lianping Xing
    • , Zhenqiang Yao
    •  & Brendan F. Boyce
  • Article
    | Open Access

    Anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) come with a dismal prognosis. Here, Yoo and colleagues reveal the genomic and transcriptomic landscape of ATC and DTC, highlighting potential therapeutic vulnerabilities.

    • Seong-Keun Yoo
    • , Young Shin Song
    • , Eun Kyung Lee
    • , Jinha Hwang
    • , Hwan Hee Kim
    • , Gyeongseo Jung
    • , Young A Kim
    • , Su-jin Kim
    • , Sun Wook Cho
    • , Jae-Kyung Won
    • , Eun-Jae Chung
    • , Jong-Yeon Shin
    • , Kyu Eun Lee
    • , Jong-Il Kim
    • , Young Joo Park
    •  & Jeong-Sun Seo
  • Article
    | Open Access

    Type 2 diabetes is associated with islet amyloid deposits derived from islet amyloid polypeptide (IAPP) expressed by β-cells. Here the authors show that IAPP misfolded protein stress induces the hypoxia inducible factor 1 alpha injury repair pathway and activates survival metabolic changes mediated by PFKFB3.

    • Chiara Montemurro
    • , Hiroshi Nomoto
    • , Lina Pei
    • , Vishal S. Parekh
    • , Kenny E. Vongbunyong
    • , Suryakiran Vadrevu
    • , Tatyana Gurlo
    • , Alexandra E. Butler
    • , Rohan Subramaniam
    • , Eleni Ritou
    • , Orian S. Shirihai
    • , Leslie S. Satin
    • , Peter C. Butler
    •  & Slavica Tudzarova
  • Article
    | Open Access

    Men and women differ in their risk of developing coronary artery disease, in part due to differences in their levels of sex hormones. Here, AlSiraj et al. show that the XX sex genotype regulates lipid metabolism and promotes atherosclerosis independently of sex hormones in mice.

    • Yasir AlSiraj
    • , Xuqi Chen
    • , Sean E. Thatcher
    • , Ryan E. Temel
    • , Lei Cai
    • , Eric Blalock
    • , Wendy Katz
    • , Heba M. Ali
    • , Michael Petriello
    • , Pan Deng
    • , Andrew J. Morris
    • , Xuping Wang
    • , Aldons J. Lusis
    • , Arthur P. Arnold
    • , Karen Reue
    • , Katherine Thompson
    • , Patrick Tso
    •  & Lisa A. Cassis
  • Article
    | Open Access

    Our understanding of the functional link between differential DNA methylation and type 2 diabetes and obesity remains limited. Here the authors present a blood-based EWAS of fasting glucose and insulin among 4808 non-diabetic Europeans and identify nine CpGs not previously implicated in glucose, insulin homeostasis and diabetes.

    • Jun Liu
    • , Elena Carnero-Montoro
    • , Jenny van Dongen
    • , Samantha Lent
    • , Ivana Nedeljkovic
    • , Symen Ligthart
    • , Pei-Chien Tsai
    • , Tiphaine C. Martin
    • , Pooja R. Mandaviya
    • , Rick Jansen
    • , Marjolein J. Peters
    • , Liesbeth Duijts
    • , Vincent W. V. Jaddoe
    • , Henning Tiemeier
    • , Janine F. Felix
    • , Gonneke Willemsen
    • , Eco J. C. de Geus
    • , Audrey Y. Chu
    • , Daniel Levy
    • , Shih-Jen Hwang
    • , Jan Bressler
    • , Rahul Gondalia
    • , Elias L. Salfati
    • , Christian Herder
    • , Bertha A. Hidalgo
    • , Toshiko Tanaka
    • , Ann Zenobia Moore
    • , Rozenn N. Lemaitre
    • , Min A Jhun
    • , Jennifer A. Smith
    • , Nona Sotoodehnia
    • , Stefania Bandinelli
    • , Luigi Ferrucci
    • , Donna K. Arnett
    • , Harald Grallert
    • , Themistocles L. Assimes
    • , Lifang Hou
    • , Andrea Baccarelli
    • , Eric A. Whitsel
    • , Ko Willems van Dijk
    • , Najaf Amin
    • , André G. Uitterlinden
    • , Eric J. G. Sijbrands
    • , Oscar H. Franco
    • , Abbas Dehghan
    • , Tim D. Spector
    • , Josée Dupuis
    • , Marie-France Hivert
    • , Jerome I. Rotter
    • , James B. Meigs
    • , James S. Pankow
    • , Joyce B. J. van Meurs
    • , Aaron Isaacs
    • , Dorret I. Boomsma
    • , Jordana T. Bell
    • , Ayşe Demirkan
    •  & Cornelia M. van Duijn
  • Article
    | Open Access

    Pancreatic beta-cell glucose metabolism is coupled to insulin secretion. Here the authors set out to characterize changes in beta-cell metabolism in hyperglycemia which may contribute to insufficient insulin secretion in type 2 diabetes and, using a multi-omics approach, find that mitochondrial metabolism is perturbed.

    • Elizabeth Haythorne
    • , Maria Rohm
    • , Martijn van de Bunt
    • , Melissa F. Brereton
    • , Andrei I. Tarasov
    • , Thomas S. Blacker
    • , Gregor Sachse
    • , Mariana Silva dos Santos
    • , Raul Terron Exposito
    • , Simon Davis
    • , Otto Baba
    • , Roman Fischer
    • , Michael R. Duchen
    • , Patrik Rorsman
    • , James I. MacRae
    •  & Frances M. Ashcroft
  • Article
    | Open Access

    The gut microbiome has been reported to be associated with obesity; here, the authors show that there are sex-specific differences in the relationship between gut microbes and abdominal obesity.

    • Yan Min
    • , Xiaoguang Ma
    • , Kris Sankaran
    • , Yuan Ru
    • , Lijin Chen
    • , Mike Baiocchi
    •  & Shankuan Zhu
  • Article
    | Open Access

    Mitochondrial uncoupling is a treatment strategy for metabolic diseases that reduces the efficiency of mitochondrial oxidative phosphorylation and ATP generation. Here the authors characterize the pharmacokinetic and therapeutic properties of the liver-localized mitochondrial uncoupler OPC-163493, which leads to amelioration of diabetes and hypertension in several rodent disease models.

    • Naohide Kanemoto
    • , Takashi Okamoto
    • , Koji Tanabe
    • , Takahiro Shimada
    • , Hitomi Minoshima
    • , Yuya Hidoh
    • , Masashi Aoyama
    • , Takashi Ban
    • , Yusuke Kobayashi
    • , Hikaru Ando
    • , Yuki Inoue
    • , Motohiro Itotani
    •  & Seiji Sato
  • Article
    | Open Access

    Risk loci for type 2 diabetes (T2D) reside in pancreatic islet enhancers. Here, the authors generate high-resolution maps of islet chromatin conformation using Hi-C which they combine with ATAC-seq and ChIP-seq data to annotate candidate target genes of enhancers and validate IGF2BP2 activity in mouse islets.

    • William W. Greenwald
    • , Joshua Chiou
    • , Jian Yan
    • , Yunjiang Qiu
    • , Ning Dai
    • , Allen Wang
    • , Naoki Nariai
    • , Anthony Aylward
    • , Jee Yun Han
    • , Nikita Kadakia
    • , Laura Regue
    • , Mei-Lin Okino
    • , Frauke Drees
    • , Dana Kramer
    • , Nicholas Vinckier
    • , Liliana Minichiello
    • , David Gorkin
    • , Joseph Avruch
    • , Kelly A. Frazer
    • , Maike Sander
    • , Bing Ren
    •  & Kyle J. Gaulton
  • Article
    | Open Access

    Berberine has lipid-lowering effects and other metabolic benefits, but it presents with poor bioavailability. Here the authors conjugate berberine to liver-targeting nanoparticles, and show increased accumulation of berberine in the liver, improved metabolic profiles and reduced atherosclerotic plaques in mice.

    • Hui-Hui Guo
    • , Chen-Lin Feng
    • , Wen-Xuan Zhang
    • , Zhi-Gang Luo
    • , Hong-Juan Zhang
    • , Ting-Ting Zhang
    • , Chen Ma
    • , Yun Zhan
    • , Rui Li
    • , Song Wu
    • , Zeper Abliz
    • , Cong Li
    • , Xiao-Lin Li
    • , Xiao-Lei Ma
    • , Lu-Lu Wang
    • , Wen-Sheng Zheng
    • , Yan-Xing Han
    •  & Jian-Dong Jiang
  • Article
    | Open Access

    The mechanisms by which organisms adapt their growth according to the availability of oxygen are incompletely understood. Here the authors identify the Drosophila fat body as a tissue regulating growth in response to oxygen sensing via a mechanism involving Hph inhibition, HIF1-a activation and insulin secretion.

    • Michael J. Texada
    • , Anne F. Jørgensen
    • , Christian F. Christensen
    • , Takashi Koyama
    • , Alina Malita
    • , Daniel K. Smith
    • , Dylan F. M. Marple
    • , E. Thomas Danielsen
    • , Sine K. Petersen
    • , Jakob L. Hansen
    • , Kenneth A. Halberg
    •  & Kim F. Rewitz
  • Article
    | Open Access

    Metabolic diseases are associated with chronic, low-grade inflammation. Here the authors show that major vault protein (MVP) suppresses NF-κB signalling in macrophages via an IRAK1–TRAF6 axis and that loss of MVP in myeloid cells exacerbates the inflammatory response in mice fed a high fat diet.

    • Jingjing Ben
    • , Bin Jiang
    • , Dongdong Wang
    • , Qingling Liu
    • , Yongjing Zhang
    • , Yu Qi
    • , Xing Tong
    • , Lili Chen
    • , Xianzhong Liu
    • , Yan Zhang
    • , Xudong Zhu
    • , Xiaoyu Li
    • , Hanwen Zhang
    • , Hui Bai
    • , Qing Yang
    • , Junqing Ma
    • , Erik A. C. Wiemer
    • , Yong Xu
    •  & Qi Chen
  • Article
    | Open Access

    Neurons expressing pro-opiomelanocortin (Pomc) regulate food intake and body weight. Here the authors show that Steroid Receptor Coactivator-1 (SRC-1) regulates the function of Pomc expressing neurons, and that rare heterozygous variants found in obese individuals lead to loss of SRC-1 function.

    • Yongjie Yang
    • , Agatha A. van der Klaauw
    • , Liangru Zhu
    • , Tessa M. Cacciottolo
    • , Yanlin He
    • , Lukas K. J. Stadler
    • , Chunmei Wang
    • , Pingwen Xu
    • , Kenji Saito
    • , Antentor Hinton Jr.
    • , Xiaofeng Yan
    • , Julia M. Keogh
    • , Elana Henning
    • , Matthew C. Banton
    • , Audrey E. Hendricks
    • , Elena G. Bochukova
    • , Vanisha Mistry
    • , Katherine L. Lawler
    • , Lan Liao
    • , Jianming Xu
    • , Stephen O’Rahilly
    • , Qingchun Tong
    • , Inês Barroso
    • , Bert W. O’Malley
    • , I. Sadaf Farooqi
    •  & Yong Xu
  • Article
    | Open Access

    TMCO1 is a recently described endoplasmic reticular Ca2+ channel. Here, the authors show it is important for osteoblast function and bone formation in mice, and identify a novel pathway linking local increases in Ca2+ at the ER surface with the posttranslational modification of RUNX2.

    • Jianwei Li
    • , Caizhi Liu
    • , Yuheng Li
    • , Qiaoxia Zheng
    • , Youjia Xu
    • , Beibei Liu
    • , Weijia Sun
    • , Yuan Li
    • , Shuhui Ji
    • , Mingwei Liu
    • , Jing Zhang
    • , Dingsheng Zhao
    • , Ruikai Du
    • , Zizhong Liu
    • , Guohui Zhong
    • , Cuiwei Sun
    • , Yanqing Wang
    • , Jinping Song
    • , Shu Zhang
    • , Jun Qin
    • , Shukuan Ling
    • , Xianhua Wang
    •  & Yingxian Li
  • Article
    | Open Access

    Fasting is known for its beneficial effects on obesity and diabetes-related health complications. Here Zhang et al. show that fasting induces expression of arginase-2 (Arg2) in the liver, and that hepatic Arg2, by suppressing the expression of the regulator of G-protein signalling 16, recapitulates the positive effects of fasting in obesity and diabetes.

    • Yiming Zhang
    • , Cassandra B. Higgins
    • , Hannah M. Fortune
    • , Phillip Chen
    • , Alicyn I. Stothard
    • , Allyson L. Mayer
    • , Benjamin M. Swarts
    •  & Brian J. DeBosch
  • Article
    | Open Access

    Parathyroid hormone (PTH) is used to treat osteoporosis, but its therapeutic mechanism remains unclear. Here, the authors show that Tgif1 is a PTH target gene, and that its deletion impairs the function of osteoblasts and PTH-induced bone formation in mice.

    • Hiroaki Saito
    • , Andreas Gasser
    • , Simona Bolamperti
    • , Miki Maeda
    • , Levi Matthies
    • , Katharina Jähn
    • , Courtney L. Long
    • , Hartmut Schlüter
    • , Marcel Kwiatkowski
    • , Vaibhav Saini
    • , Paola Divieti Pajevic
    • , Teresita Bellido
    • , Andre J. van Wijnen
    • , Khalid S. Mohammad
    • , Theresa A. Guise
    • , Hanna Taipaleenmäki
    •  & Eric Hesse
  • Article
    | Open Access

    GWAS have identified numerous genetic loci for bone mineral density (BMD) and fracture risk. Here, the authors map these variants to putative target genes using ATAC-seq and Capture C of human osteoblasts and confirm ING3 and EPDR1 as BMD genes in in vitro osteoblast differentiation experiments.

    • Alessandra Chesi
    • , Yadav Wagley
    • , Matthew E. Johnson
    • , Elisabetta Manduchi
    • , Chun Su
    • , Sumei Lu
    • , Michelle E. Leonard
    • , Kenyaita M. Hodge
    • , James A. Pippin
    • , Kurt D. Hankenson
    • , Andrew D. Wells
    •  & Struan F. A. Grant
  • Article
    | Open Access

    Glucagon-like peptide 1 (GLP-1) is released from intestinal L-cells following nutrient uptake and enhances insulin release as well as promotes satiety. Here, the authors demonstrate that GLP-1 secreting cells release ATP and that this stimulates nodose neurons and enterocytes in a paracrine manner in vitro.

    • Van B. Lu
    • , Juraj Rievaj
    • , Elisabeth A. O’Flaherty
    • , Christopher A. Smith
    • , Ramona Pais
    • , Luke A. Pattison
    • , Gwen Tolhurst
    • , Andrew B. Leiter
    • , David C. Bulmer
    • , Fiona M. Gribble
    •  & Frank Reimann