Youqiong Ye

Characterization of hypoxia-associated molecular features to aid hypoxia-targeted therapy

Latest Research

  • 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
  • Letter |

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

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

News & Comment

  • News & Views |

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

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

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

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

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

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

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

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

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

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

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

    • Philip L. S. M. Gordts
    •  & Alan R. Saltiel