Thomas Franz Erich Willnow

Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Ji A Seo, Music and Neuroimaging Lab, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
  • ,
  • Min-Cheol Kang, Music and Neuroimaging Lab, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
  • ,
  • Won-Mo Yang, Music and Neuroimaging Lab, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
  • ,
  • Won Min Hwang, Music and Neuroimaging Lab, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
  • ,
  • Sang Soo Kim, Music and Neuroimaging Lab, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
  • ,
  • Soo Hyun Hong, Music and Neuroimaging Lab, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
  • ,
  • Jee-In Heo, Department of Emergency Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
  • ,
  • Achana Vijyakumar, Music and Neuroimaging Lab, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
  • ,
  • Leandro Pereira de Moura, Music and Neuroimaging Lab, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
  • ,
  • Aykut Uner, Music and Neuroimaging Lab, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
  • ,
  • Hu Huang, Music and Neuroimaging Lab, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
  • ,
  • Seung Hwan Lee, Music and Neuroimaging Lab, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
  • ,
  • Inês S Lima, Music and Neuroimaging Lab, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
  • ,
  • Kyong Soo Park, Seoul Natl Univ Hosp, Seoul National University, Seoul National University Hospital, Dept Surg
  • ,
  • Min Seon Kim, Department of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea.
  • ,
  • Yossi Dagon, Music and Neuroimaging Lab, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
  • ,
  • Thomas E Willnow
  • Vanita Aroda, Department of Dermatology, University of California, San Diego, California; Department of Pediatrics, University of California, San Diego, California; Rady Children's Hospital, San Diego, California.
  • ,
  • Theodore P Ciaraldi, Department of Dermatology, University of California, San Diego, California; Department of Pediatrics, University of California, San Diego, California; Rady Children's Hospital, San Diego, California.
  • ,
  • Robert R Henry, Department of Dermatology, University of California, San Diego, California; Department of Pediatrics, University of California, San Diego, California; Rady Children's Hospital, San Diego, California.
  • ,
  • Young-Bum Kim, Music and Neuroimaging Lab, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA

Crosstalk between liver and skeletal muscle is vital for glucose homeostasis. Hepatokines, liver-derived proteins that play an important role in regulating muscle metabolism, are important to this communication. Here we identify apolipoprotein J (ApoJ) as a novel hepatokine targeting muscle glucose metabolism and insulin sensitivity through a low-density lipoprotein receptor-related protein-2 (LRP2)-dependent mechanism, coupled with the insulin receptor (IR) signaling cascade. In muscle, LRP2 is necessary for insulin-dependent IR internalization, an initial trigger for insulin signaling, that is crucial in regulating downstream signaling and glucose uptake. Of physiologic significance, deletion of hepatic ApoJ or muscle LRP2 causes insulin resistance and glucose intolerance. In patients with polycystic ovary syndrome and insulin resistance, pioglitazone-induced improvement of insulin action is associated with an increase in muscle ApoJ and LRP2 expression. Thus, the ApoJ-LRP2 axis is a novel endocrine circuit that is central to the maintenance of normal glucose homeostasis and insulin sensitivity.

Original languageEnglish
JournalNature Communications
Volume11
Issue1
Pages (from-to)2024
ISSN2041-1723
DOIs
Publication statusPublished - 24 Apr 2020
Externally publishedYes

    Research areas

  • Adult, Animals, Cell Line, Clusterin/blood, Disease Models, Animal, Female, Glucose/metabolism, Glucose Clamp Technique, Humans, Hypoglycemic Agents/pharmacology, Insulin/metabolism, Insulin Resistance, Liver/metabolism, Low Density Lipoprotein Receptor-Related Protein-2/genetics, Male, Mice, Mice, Knockout, Muscle, Skeletal/metabolism, Pioglitazone/pharmacology, Polycystic Ovary Syndrome/blood, Receptor, Insulin/metabolism, Signal Transduction/drug effects

See relations at Aarhus University Citationformats

ID: 196614827