Endocrinology

  • Article
    | Open Access

    The location and extent of intranasal oxytocin brain penetrance has not been shown. Here the authors show that oxytocin, administered intranasally, enters brain regions along the trajectories of the olfactory and trigeminal nerves and there, reaches biologically relevant concentrations.

    • M. R. Lee
    • , T. A. Shnitko
    • , S. W. Blue
    • , A. V. Kaucher
    • , A. J. Winchell
    • , D. W. Erikson
    • , K. A. Grant
    •  & L. Leggio
  • Article
    | Open Access

    Obesity and type 2 diabetes (T2D) are metabolic disorders characterized by insulin resistance in skeletal muscle. Here, the authors map skeletal muscle enhancer elements dynamically regulated after exposure to free fatty acid palmitate or inflammatory cytokine TNFα and identify target genes involved in metabolic dysfunction in skeletal muscle.

    • Kristine Williams
    • , Lars R. Ingerslev
    • , Jette Bork-Jensen
    • , Martin Wohlwend
    • , Ann Normann Hansen
    • , Lewin Small
    • , Rasmus Ribel-Madsen
    • , Arne Astrup
    • , Oluf Pedersen
    • , Johan Auwerx
    • , Christopher T. Workman
    • , Niels Grarup
    • , Torben Hansen
    •  & Romain Barrès
  • Article
    | Open Access

    Adrenal aldosterone production is regulated by plasma angiotensin and potassium levels. Here the authors report that the neuropeptide substance P stimulates aldosterone production via neurokinin type 1 receptors (NK1R), and report a proof-of-concept placebo controlled clinical trial showing that a NK1R antagonist decreases aldosterone levels.

    • Julien Wils
    • , Céline Duparc
    • , Anne-Françoise Cailleux
    • , Antoine-Guy Lopez
    • , Caroline Guiheneuf
    • , Isabelle Boutelet
    • , Hadrien-Gaël Boyer
    • , Christophe Dubessy
    • , Saloua Cherifi
    • , Bruno Cauliez
    • , Françoise Gobet
    • , Guillaume Defortescu
    • , Jean-François Ménard
    • , Estelle Louiset
    •  & Hervé Lefebvre
  • Article
    | Open Access

    The cytokine IFNα is expressed in the islets of individuals with type 1 diabetes and contributes to local inflammation and destruction of beta cells. Here, the authors provide a global multiomics view of IFNα-induced changes in human beta cells at the level of chromatin, mRNA and protein expression.

    • Maikel L. Colli
    • , Mireia Ramos-Rodríguez
    • , Ernesto S. Nakayasu
    • , Maria I. Alvelos
    • , Miguel Lopes
    • , Jessica L. E. Hill
    • , Jean-Valery Turatsinze
    • , Alexandra Coomans de Brachène
    • , Mark A. Russell
    • , Helena Raurell-Vila
    • , Angela Castela
    • , Jonàs Juan-Mateu
    • , Bobbie-Jo M. Webb-Robertson
    • , Lars Krogvold
    • , Knut Dahl-Jorgensen
    • , Lorella Marselli
    • , Piero Marchetti
    • , Sarah J. Richardson
    • , Noel G. Morgan
    • , Thomas O. Metz
    • , Lorenzo Pasquali
    •  & Décio L. Eizirik
  • Article
    | Open Access

    Disease stress-induced cardiac hypertrophy is a major mechanism of pathological cardiac remodeling. Here, the authors unveil a previously unrecognized role of a FoxO1–Dio2 signaling axis in maladaptive, afterload-induced cardiac hypertrophy and intracellular thyroid hormone homeostasis.

    • Anwarul Ferdous
    • , Zhao V. Wang
    • , Yuxuan Luo
    • , Dan L. Li
    • , Xiang Luo
    • , Gabriele G. Schiattarella
    • , Francisco Altamirano
    • , Herman I. May
    • , Pavan K. Battiprolu
    • , Annie Nguyen
    • , Beverly A. Rothermel
    • , Sergio Lavandero
    • , Thomas G. Gillette
    •  & Joseph A. Hill
  • Article
    | Open Access

    During the progression of type 2 diabetes, insulin-producing β-cells can lose their identity and become reprogrammed into other cell types. Here the authors show that murine diabetic β-cells require the protein Raptor for maintaining β-cell health and preventing them from turning into α-cells, independent of Raptor’s involvement in regulating blood sugar levels.

    • Qinglei Yin
    • , Qicheng Ni
    • , Yichen Wang
    • , Hongli Zhang
    • , Wenyi Li
    • , Aifang Nie
    • , Shu Wang
    • , Yanyun Gu
    • , Qidi Wang
    •  & Guang Ning
  • Article
    | Open Access

    The genetic basis of prolactinomas remains poorly understood. Here, the authors find a recurrent hotspot somatic mutation in the splicing factor 3 subunit B1 (SF3B1R625H) in prolactinomas, and show that this mutation causes aberrant splicing of ESRRG mRNA leading to up-regulation of prolactin.

    • Chuzhong Li
    • , Weiyan Xie
    • , Jared S. Rosenblum
    • , Jianyu Zhou
    • , Jing Guo
    • , Yazhou Miao
    • , Yutao Shen
    • , Hongyun Wang
    • , Lei Gong
    • , Mingxuan Li
    • , Sida Zhao
    • , Sen Cheng
    • , Haibo Zhu
    • , Tao Jiang
    • , Shiying Ling
    • , Fei Wang
    • , Hongwei Zhang
    • , Mingshan Zhang
    • , Yanming Qu
    • , Qi Zhang
    • , Guilin Li
    • , Junmei Wang
    • , Jun Ma
    • , Zhengping Zhuang
    •  & Yazhuo Zhang
  • Article
    | Open Access

    Obesity is a global pandemic with limited treatment options. Here, the authors show evidence in mice that the mitochondrial uncoupler BAM15 effectively induces fat loss without affecting food intake or compromising lean body mass.

    • Stephanie J. Alexopoulos
    • , Sing-Young Chen
    • , Amanda E. Brandon
    • , Joseph M. Salamoun
    • , Frances L. Byrne
    • , Christopher J. Garcia
    • , Martina Beretta
    • , Ellen M. Olzomer
    • , Divya P. Shah
    • , Ashleigh M. Philp
    • , Stefan R. Hargett
    • , Robert T. Lawrence
    • , Brendan Lee
    • , James Sligar
    • , Pascal Carrive
    • , Simon P. Tucker
    • , Andrew Philp
    • , Carolin Lackner
    • , Nigel Turner
    • , Gregory J. Cooney
    • , Webster L. Santos
    •  & Kyle L. Hoehn
  • Article
    | Open Access

    Beta-adrenergic stimulation of brown adipose tissue leads to thermogenesis via the activating transcription factor 2 (ATF2) mediated expression of the thermogenic genes Ucp1 and Pgc-1α. Here, the authors show that the scaffold protein p62 regulates brown adipose tissue function through modifying ATF2 genomic binding and subsequent Ucp1 and Pgc-1α induction.

    • Katrin Fischer
    • , Anna Fenzl
    • , Dianxin Liu
    • , Kenneth A. Dyar
    • , Maximilian Kleinert
    • , Markus Brielmeier
    • , Christoffer Clemmensen
    • , Anna Fedl
    • , Brian Finan
    • , Andre Gessner
    • , Martin Jastroch
    • , Jianfeng Huang
    • , Susanne Keipert
    • , Martin Klingenspor
    • , Jens C. Brüning
    • , Manfred Kneilling
    • , Florian C. Maier
    • , Ahmed E. Othman
    • , Bernd J. Pichler
    • , Ines Pramme-Steinwachs
    • , Stephan Sachs
    • , Angelika Scheideler
    • , Wolfgang M. Thaiss
    • , Henriette Uhlenhaut
    • , Siegfried Ussar
    • , Stephen C. Woods
    • , Julia Zorn
    • , Kerstin Stemmer
    • , Sheila Collins
    • , Maria Diaz-Meco
    • , Jorge Moscat
    • , Matthias H. Tschöp
    •  & Timo D. Müller
  • Article
    | Open Access

    Glucose-sensing neurons are found in the ventromedial hypothalamic nucleus (VMH). Here the authors identify the role of estrogen receptor-α expressing neurons in the ventrolateral subdivision of the VMH in sensing hypoglycemia.

    • Yanlin He
    • , Pingwen Xu
    • , Chunmei Wang
    • , Yan Xia
    • , Meng Yu
    • , Yongjie Yang
    • , Kaifan Yu
    • , Xing Cai
    • , Na Qu
    • , Kenji Saito
    • , Julia Wang
    • , Ilirjana Hyseni
    • , Matthew Robertson
    • , Badrajee Piyarathna
    • , Min Gao
    • , Sohaib A. Khan
    • , Feng Liu
    • , Rui Chen
    • , Cristian Coarfa
    • , Zhongming Zhao
    • , Qingchun Tong
    • , Zheng Sun
    •  & Yong Xu
  • Article
    | Open Access

    Brown adipose tissue, known produce heat by metabolizing fat, is also secretes molecules capable of communicating with other organs. Here the authors show that brown adipose tissue secretes kininogen, a component of heat system regulation, that provides auto-regulatory inhibitory signaling in brown adipose tissue.

    • Marion Peyrou
    • , Rubén Cereijo
    • , Tania Quesada-López
    • , Laura Campderrós
    • , Aleix Gavaldà-Navarro
    • , Laura Liñares-Pose
    • , Elena Kaschina
    • , Thomas Unger
    • , Miguel López
    • , Marta Giralt
    •  & Francesc Villarroya
  • Article
    | Open Access

    The mechanisms underlying cardiac inflammation in diabetic cardiomyopathy are incompletely understood. Here the authors show that advanced glycation end products bind to the TLR4 co-receptor MD2 initiating pro-inflammatory pathways.

    • Yi Wang
    • , Wu Luo
    • , Jibo Han
    • , Zia A. Khan
    • , Qilu Fang
    • , Yiyi Jin
    • , Xuemei Chen
    • , Yali Zhang
    • , Meihong Wang
    • , Jianchang Qian
    • , Weijian Huang
    • , Hazel Lum
    • , Gaojun Wu
    •  & Guang Liang
  • Article
    | Open Access

    SGLT2 inhibitors, a class of type 2 diabetes medication, reduce cardiovascular events in patients beyond expectation from blood sugar control. Here the authors report a randomized controlled trial showing that SGLT2 inhibitors reduce inflammasome activation in peripheral macrophages, which may contribute to the cardiovascular protection.

    • So Ra Kim
    • , Sang-Guk Lee
    • , Soo Hyun Kim
    • , Jin Hee Kim
    • , Eunhye Choi
    • , Wonhee Cho
    • , John Hoon Rim
    • , Inhwa Hwang
    • , Chan Joo Lee
    • , Minyoung Lee
    • , Chang-Myung Oh
    • , Justin Y. Jeon
    • , Heon Yung Gee
    • , Jeong-Ho Kim
    • , Byung-Wan Lee
    • , Eun Seok Kang
    • , Bong-Soo Cha
    • , Myung-Shik Lee
    • , Je-Wook Yu
    • , Jin Won Cho
    • , Jung-Sun Kim
    •  & Yong-ho Lee
  • Article
    | Open Access

    Hyper-insulinemia associated with excess calorie intake may cause metabolic dysfunction. Here the authors report that mice with partially reduced insulin receptor expression in peripheral tissues are protected from and experience reversal of fatty liver disease.

    • Troy L. Merry
    • , Chris P. Hedges
    • , Stewart W. Masson
    • , Beate Laube
    • , Doris Pöhlmann
    • , Stephan Wueest
    • , Michael E. Walsh
    • , Myrtha Arnold
    • , Wolfgang Langhans
    • , Daniel Konrad
    • , Kim Zarse
    •  & Michael Ristow
  • Article
    | Open Access

    Hepatokines are proteins secreted by the liver that can regulate whole body metabolism. Here the authors identify apolipoprotein J as a hepatokine that regulates muscle glucose metabolism and insulin resistance through a low-density lipoprotein receptor-related protein−2 mediated mechanism in mice.

    • Ji A Seo
    • , Min-Cheol Kang
    • , Won-Mo Yang
    • , Won Min Hwang
    • , Sang Soo Kim
    • , Soo Hyun Hong
    • , Jee-In Heo
    • , Achana Vijyakumar
    • , Leandro Pereira de Moura
    • , Aykut Uner
    • , Hu Huang
    • , Seung Hwan Lee
    • , Inês S. Lima
    • , Kyong Soo Park
    • , Min Seon Kim
    • , Yossi Dagon
    • , Thomas E. Willnow
    • , Vanita Aroda
    • , Theodore P. Ciaraldi
    • , Robert R. Henry
    •  & Young-Bum Kim
  • Article
    | Open Access

    Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Here, the authors use 1H-MRS methodology to show hepatic SFA fraction is a measure of DNL and specifically may hamper hepatic insulin sensitivity.

    • Kay H. M. Roumans
    • , Lucas Lindeboom
    • , Pandichelvam Veeraiah
    • , Carlijn M. E. Remie
    • , Esther Phielix
    • , Bas Havekes
    • , Yvonne M. H. Bruls
    • , Martijn C. G. J. Brouwers
    • , Marcus Ståhlman
    • , Marjan Alssema
    • , Harry P. F. Peters
    • , Renée de Mutsert
    • , Bart Staels
    • , Marja-Riitta Taskinen
    • , Jan Borén
    • , Patrick Schrauwen
    •  & Vera B. Schrauwen-Hinderling
  • Article
    | Open Access

    Brain insulin action regulates eating behavior and whole-body energy fluxes, however the impact of brain insulin resistance on long-term weight and body fat composition is unknown. Here, the authors show that high brain insulin sensitivity is linked to weight loss during lifestyle intervention and associates with a favorable body fat distribution.

    • Stephanie Kullmann
    • , Vera Valenta
    • , Robert Wagner
    • , Otto Tschritter
    • , Jürgen Machann
    • , Hans-Ulrich Häring
    • , Hubert Preissl
    • , Andreas Fritsche
    •  & Martin Heni
  • Article
    | Open Access

    Understanding the regulatory mechanisms governing brown and beige adipose mediated thermogenesis is of interest in order to develop therapeutic strategies to treat obesity. Here, the authors show that adipocyte-expressed apoptosis signal-regulating kinase 1 (ASK1) inhibits browning in response to cold, β3 receptor activation, and LPS.

    • Fabrizio C. Lucchini
    • , Stephan Wueest
    • , Tenagne D. Challa
    • , Flurin Item
    • , Salvatore Modica
    • , Marcela Borsigova
    • , Yulia Haim
    • , Christian Wolfrum
    • , Assaf Rudich
    •  & Daniel Konrad
  • Article
    | Open Access

    How hormonal signaling in the mammary epithelium controls the surrounding extracellular matrix is unclear. Here, the authors show that a secreted protease, Adamts18, induced by upstream estrogen-progesterone activated Wnt4 in myoepithelial cells, remodels the basement membrane and contributes to mammary epithelial stemness.

    • Dalya Ataca
    • , Patrick Aouad
    • , Céline Constantin
    • , Csaba Laszlo
    • , Manfred Beleut
    • , Marie Shamseddin
    • , Renuga Devi Rajaram
    • , Rachel Jeitziner
    • , Timothy J. Mead
    • , Marian Caikovski
    • , Philipp Bucher
    • , Giovanna Ambrosini
    • , Suneel S. Apte
    •  & Cathrin Brisken
  • Article
    | Open Access

    Exercise has been shown to be an effective approach to ameliorate metabolic disease in mice housed at ambient temperatures, a condition of mild cold stress to mice. Here the authors show that molecular and metabolic adaptations to exercise are blunted when mice are housed in thermoneutral conditions.

    • Steffen H. Raun
    • , Carlos Henriquez-Olguín
    • , Iuliia Karavaeva
    • , Mona Ali
    • , Lisbeth L. V. Møller
    • , Witold Kot
    • , Josué L. Castro-Mejía
    • , Dennis Sandris Nielsen
    • , Zachary Gerhart-Hines
    • , Erik A. Richter
    •  & Lykke Sylow
  • Article
    | Open Access

    Age at voice-breaking is used to determine puberty timing in men, recall of which is considered less accurate than age at first menarche in women. Here, the authors perform multi-trait GWAS for male puberty timing by including both age at voice breaking and age of first facial hair for improved phenotype definition and power.

    • Ben Hollis
    • , Felix R. Day
    • , Alexander S. Busch
    • , Deborah J. Thompson
    • , Ana Luiza G. Soares
    • , Paul R. H. J. Timmers
    • , Alex Kwong
    • , Doug F. Easton
    • , Peter K. Joshi
    • , Nicholas J. Timpson
    • , Rosalind A. Eeles
    • , Brian E. Henderson
    • , Christopher A. Haiman
    • , Zsofia Kote-Jarai
    • , Fredrick R. Schumacher
    • , Ali Amin Al Olama
    • , Sara Benlloch
    • , Kenneth Muir
    • , Sonja I. Berndt
    • , David V. Conti
    • , Fredrik Wiklund
    • , Stephen Chanock
    • , Susan Gapstur
    • , Victoria L. Stevens
    • , Catherine M. Tangen
    • , Jyotsna Batra
    • , Judith Clements
    • , Wayne Tilley
    • , Gail P. Risbridger
    • , Judith Clements
    • , Lisa Horvath
    • , Renea Taylor
    • , Vanessa Hayes
    • , Lisa Butler
    • , Trina Yeadon
    • , Allison Eckert
    • , Pamela Saunders
    • , Anne-Maree Haynes
    • , Melissa Papargiris
    • , Srilakshmi Srinivasan
    • , Mary-Anne Kedda
    • , Leire Moya
    • , Jyotsna Batra
    • , Henrik Gronberg
    • , Nora Pashayan
    • , Johanna Schleutker
    • , Demetrius Albanes
    • , Alicja Wolk
    • , Catharine West
    • , Lorelei Mucci
    • , Géraldine Cancel-Tassin
    • , Stella Koutros
    • , Karina Dalsgaard Sorensen
    • , Eli Marie Grindedal
    • , David E. Neal
    • , Freddie C. Hamdy
    • , Jenny L. Donovan
    • , Ruth C. Travis
    • , Robert J. Hamilton
    • , Sue Ann Ingles
    • , Barry S. Rosenstein
    • , Yong-Jie Lu
    • , Graham G. Giles
    • , Adam S. Kibel
    • , Ana Vega
    • , Manolis Kogevinas
    • , Kathryn L. Penney
    • , Jong Y. Park
    • , Janet L. Stanford
    • , Cezary Cybulski
    • , Børge G. Nordestgaard
    • , Hermann Brenner
    • , Christiane Maier
    • , Jeri Kim
    • , Esther M. John
    • , Manuel R. Teixeira
    • , Susan L. Neuhausen
    • , Kim De Ruyck
    • , Azad Razack
    • , Lisa F. Newcomb
    • , Davor Lessel
    • , Radka Kaneva
    • , Nawaid Usmani
    • , Frank Claessens
    • , Paul A. Townsend
    • , Manuela Gago-Dominguez
    • , Monique J. Roobol
    • , Florence Menegaux
    • , Kay-Tee Khaw
    • , Lisa Cannon-Albright
    • , Hardev Pandha
    • , Stephen N. Thibodeau
    • , Michelle Agee
    • , Babak Alipanahi
    • , Adam Auton
    • , Robert K. Bell
    • , Katarzyna Bryc
    • , Sarah L. Elson
    • , Pierre Fontanillas
    • , Nicholas A. Furlotte
    • , David A. Hinds
    • , Karen E. Huber
    • , Aaron Kleinman
    • , Nadia K. Litterman
    • , Matthew H. McIntyre
    • , Joanna L. Mountain
    • , Elizabeth S. Noblin
    • , Carrie A. M. Northover
    • , Steven J. Pitts
    • , J. Fah Sathirapongsasuti
    • , Olga V. Sazonova
    • , Janie F. Shelton
    • , Suyash Shringarpure
    • , Chao Tian
    • , Joyce Y. Tung
    • , Vladimir Vacic
    • , Catherine H. Wilson
    • , Ken K. Ong
    •  & John R. B. Perry
  • Article
    | Open Access

    Genetic variants in the FAM13A locus have been associated with anthropometric and glycemic traits. Here, using fine-mapping, in vitro knockdown studies in pre-adipocytes and in vivo knockout in mice, the authors show that FAM13A is involved in regulating fat distribution and metabolic traits.

    • Mohsen Fathzadeh
    • , Jiehan Li
    • , Abhiram Rao
    • , Naomi Cook
    • , Indumathi Chennamsetty
    • , Marcus Seldin
    • , Xiang Zhou
    • , Panjamaporn Sangwung
    • , Michael J. Gloudemans
    • , Mark Keller
    • , Allan Attie
    • , Jing Yang
    • , Martin Wabitsch
    • , Ivan Carcamo-Orive
    • , Yuko Tada
    • , Aldons J. Lusis
    • , Myung Kyun Shin
    • , Cliona M. Molony
    • , Tracey McLaughlin
    • , Gerald Reaven
    • , Stephen B. Montgomery
    • , Dermot Reilly
    • , Thomas Quertermous
    • , Erik Ingelsson
    •  & Joshua W. Knowles
  • Article
    | Open Access

    hPSCs in culture acquire a more naïve pluripotent state upon tankyrase inhibition. Here, the authors show that tankyrase inhibitor-regulated naïve hiPSCs from diabetic donors generate more vascular progenitors and more efficient engraftment into mouse retina than conventional PSCs.

    • Tea Soon Park
    • , Ludovic Zimmerlin
    • , Rebecca Evans-Moses
    • , Justin Thomas
    • , Jeffrey S. Huo
    • , Riya Kanherkar
    • , Alice He
    • , Nensi Ruzgar
    • , Rhonda Grebe
    • , Imran Bhutto
    • , Michael Barbato
    • , Michael A. Koldobskiy
    • , Gerard Lutty
    •  & Elias T. Zambidis
  • Article
    | Open Access

    Heterogeneous nuclear ribonucleoproteins (hnRNPs) play critical roles in the biogenesis, localization and transport of RNA. Here authors investigate a role for hnRNPs in sterol metabolism in mice and provide insights into their role in selective promoter activation.

    • Zhengyi Zhang
    • , An-Chieh Feng
    • , David Salisbury
    • , Xin Liu
    • , Xiaohui Wu
    • , Jason Kim
    • , Irina Lapina
    • , Dan Wang
    • , Brennan Lee
    • , Josue Fraga
    • , Calvin Pan
    • , Kevin J. Williams
    • , Aldons J. Lusis
    • , Phil Scumpia
    •  & Tamer Sallam
  • Article
    | Open Access

    Parabens are preservatives widely used in consumer products including cosmetics and food. Here the authors demonstrate that maternal paraben exposure may contribute to childhood overweight development by an altered neuronal appetite regulation.

    • Beate Leppert
    • , Sandra Strunz
    • , Bettina Seiwert
    • , Linda Schlittenbauer
    • , Rita Schlichting
    • , Christiane Pfeiffer
    • , Stefan Röder
    • , Mario Bauer
    • , Michael Borte
    • , Gabriele I. Stangl
    • , Torsten Schöneberg
    • , Angela Schulz
    • , Isabell Karkossa
    • , Ulrike E. Rolle-Kampczyk
    • , Loreen Thürmann
    • , Martin von Bergen
    • , Beate I. Escher
    • , Kristin M. Junge
    • , Thorsten Reemtsma
    • , Irina Lehmann
    •  & Tobias Polte
  • Article
    | Open Access

    Despite widespread transcription of LncRNA in mammalian systems, their contribution to metabolic homeostasis at the cellular and tissue level remains elusive. Here Pradas-Juni et al. describe a transcription factor–LncRNA pathway that couples hepatocyte nutrient sensing to regulation of glucose metabolism in mice.

    • Marta Pradas-Juni
    • , Nils R. Hansmeier
    • , Jenny C. Link
    • , Elena Schmidt
    • , Bjørk Ditlev Larsen
    • , Paul Klemm
    • , Nicola Meola
    • , Hande Topel
    • , Rute Loureiro
    • , Ines Dhaouadi
    • , Christoph A. Kiefer
    • , Robin Schwarzer
    • , Sajjad Khani
    • , Matteo Oliverio
    • , Motoharu Awazawa
    • , Peter Frommolt
    • , Joerg Heeren
    • , Ludger Scheja
    • , Markus Heine
    • , Christoph Dieterich
    • , Hildegard Büning
    • , Ling Yang
    • , Haiming Cao
    • , Dario F. De Jesus
    • , Rohit N. Kulkarni
    • , Branko Zevnik
    • , Simon E. Tröder
    • , Uwe Knippschild
    • , Peter A. Edwards
    • , Richard G. Lee
    • , Masayuki Yamamoto
    • , Igor Ulitsky
    • , Eduardo Fernandez-Rebollo
    • , Thomas Q. de Aguiar Vallim
    •  & Jan-Wilhelm Kornfeld
  • Article
    | Open Access

    T cells are involved in the bone loss induced by parathyroid hormone (PTH), but their origin is unknown. Here, the authors show that the intestinal microbiota is required for PTH to induce bone loss and describes mechanisms for microbiota-mediated gut–bone crosstalk in mouse models of hyperparathyroidism.

    • Mingcan Yu
    • , Abdul Malik Tyagi
    • , Jau-Yi Li
    • , Jonathan Adams
    • , Timothy L. Denning
    • , M. Neale Weitzmann
    • , Rheinallt M. Jones
    •  & Roberto Pacifici
  • Article
    | Open Access

    Glucagon-like peptide-1 receptor is an important regulator of appetite and glucose homeostasis. Here the authors describe super-resolution microscopy and in vivo imaging compatible fluorescent probes, which reveal endogenous glucagon-like peptide-1 receptor distribution and dynamics in islets and brain.

    • Julia Ast
    • , Anastasia Arvaniti
    • , Nicholas H. F. Fine
    • , Daniela Nasteska
    • , Fiona B. Ashford
    • , Zania Stamataki
    • , Zsombor Koszegi
    • , Andrea Bacon
    • , Ben J. Jones
    • , Maria A. Lucey
    • , Shugo Sasaki
    • , Daniel I. Brierley
    • , Benoit Hastoy
    • , Alejandra Tomas
    • , Giuseppe D’Agostino
    • , Frank Reimann
    • , Francis C. Lynn
    • , Christopher A. Reissaus
    • , Amelia K. Linnemann
    • , Elisa D’Este
    • , Davide Calebiro
    • , Stefan Trapp
    • , Kai Johnsson
    • , Tom Podewin
    • , Johannes Broichhagen
    •  & David J. Hodson
  • Article
    | Open Access

    An endothelial cell subtype, expressing endomucin and CD31, has been reported to couple angiogenesis with osteogenesis. Here, the authors show that loss of ZEB1 in these cells epigenetically suppresses Notch signaling, leading to impaired angiogenesis and osteogenesis, and that Zeb1 delivery via liposomes ameliorates bone loss in osteoporotic mice

    • Rong Fu
    • , Wen-Cong Lv
    • , Ying Xu
    • , Mu-Yun Gong
    • , Xiao-Jie Chen
    • , Nan Jiang
    • , Yan Xu
    • , Qing-Qiang Yao
    • , Lei Di
    • , Tao Lu
    • , Li-Ming Wang
    • , Ran Mo
    •  & Zhao-Qiu Wu
  • Article
    | Open Access

    Human antigen R (HuR) is an RNA binding protein that promotes mRNA stability. Here the authors show that HuR represses adipogenesis in white and brown adipose tissue by stabilizing Insig1 and other targets.

    • Diana Teh Chee Siang
    • , Yen Ching Lim
    • , Aung Maung Maung Kyaw
    • , Khaing Nwe Win
    • , Sook Yoong Chia
    • , Ufuk Degirmenci
    • , Xiang Hu
    • , Bryan C. Tan
    • , Arcinas Camille Esther Walet
    • , Lei Sun
    •  & Dan Xu
  • Article
    | Open Access

    Diabetic eye disease is a cause of preventable blindness and accurate and timely referral of patients with diabetic macular edema is important to start treatment. Here the authors present a deep learning model that can predict the presence of diabetic macular edema from color fundus photographs with superior specificity and positive predictive value compared to retinal specialists.

    • Avinash V. Varadarajan
    • , Pinal Bavishi
    • , Paisan Ruamviboonsuk
    • , Peranut Chotcomwongse
    • , Subhashini Venugopalan
    • , Arunachalam Narayanaswamy
    • , Jorge Cuadros
    • , Kuniyoshi Kanai
    • , George Bresnick
    • , Mongkol Tadarati
    • , Sukhum Silpa-archa
    • , Jirawut Limwattanayingyong
    • , Variya Nganthavee
    • , Joseph R. Ledsam
    • , Pearse A. Keane
    • , Greg S. Corrado
    • , Lily Peng
    •  & Dale R. Webster
  • Article
    | Open Access

    Anti-resorptive bone therapies also inhibit bone formation, as osteoclasts secrete factors that stimulate bone formation by osteoblasts. Here, the authors identify osteoclast-secreted factors that couple bone resorption to bone formation in healthy subjects, and show that osteoclast-derived DPP4 may be a factor coupling bone resorption to energy metabolism.

    • Megan M. Weivoda
    • , Chee Kian Chew
    • , David G. Monroe
    • , Joshua N. Farr
    • , Elizabeth J. Atkinson
    • , Jennifer R. Geske
    • , Brittany Eckhardt
    • , Brianne Thicke
    • , Ming Ruan
    • , Amanda J. Tweed
    • , Louise K. McCready
    • , Robert A. Rizza
    • , Aleksey Matveyenko
    • , Moustapha Kassem
    • , Thomas Levin Andersen
    • , Adrian Vella
    • , Matthew T. Drake
    • , Bart L. Clarke
    • , Merry Jo Oursler
    •  & Sundeep Khosla
  • 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

    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

    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

    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 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

    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

    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

    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

    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