Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Using human genetics to understand the disease impacts of testosterone in men and women

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. EZH2 is a potential therapeutic target for H3K27M-mutant pediatric gliomas

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Recurrent MET fusion genes represent a drug target in pediatric glioblastoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. FoxA1 directs the lineage and immunosuppressive properties of a novel regulatory T cell population in EAE and MS

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Gain-of-function mutation in the voltage-gated potassium channel gene KCNQ1 and glucose-stimulated hypoinsulinemia - case report

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Sex-specific estrogen levels and reference intervals from infancy to late adulthood determined by LC-MS/MS

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Copeptin, a surrogate marker for arginine vasopressin secretion, is positively associated with glucagon

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Olof S Dallner
  • Jill M Marinis
  • Yi-Hsueh Lu
  • Kivanc Birsoy
  • Emory Werner
  • Gulya Fayzikhodjaeva
  • Brian D Dill
  • Henrik Molina
  • Arden Moscati
  • Zoltán Kutalik
  • Pedro Marques-Vidal
  • Tuomas O Kilpeläinen
  • Niels Grarup
  • Allan Linneberg
  • Yinxin Zhang
  • Roger Vaughan
  • Ruth J F Loos
  • Mitchell A Lazar
  • Jeffrey M Friedman
View graph of relations

Quantitative changes in leptin concentration lead to alterations in food intake and body weight, but the regulatory mechanisms that control leptin gene expression are poorly understood. Here we report that fat-specific and quantitative leptin expression is controlled by redundant cis elements and trans factors interacting with the proximal promoter together with a long noncoding RNA (lncOb). Diet-induced obese mice lacking lncOb show increased fat mass with reduced plasma leptin levels and lose weight after leptin treatment, whereas control mice do not. Consistent with this finding, large-scale genetic studies of humans reveal a significant association of single-nucleotide polymorphisms (SNPs) in the region of human lncOb with lower plasma leptin levels and obesity. These results show that reduced leptin gene expression can lead to a hypoleptinemic, leptin-responsive form of obesity and provide a framework for elucidating the pathogenic mechanism in the subset of obese patients with low endogenous leptin levels.

Original languageEnglish
JournalNature Medicine
Volume25
Issue number3
Pages (from-to)507-516
Number of pages10
ISSN1078-8956
DOIs
Publication statusPublished - Mar 2019

ID: 56779597