Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Loss of Function of GALNT2 Lowers High-Density Lipoproteins in Humans, Nonhuman Primates, and Rodents

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Mechanisms Preserving Insulin Action during High Dietary Fat Intake

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Patients with Obesity Caused by Melanocortin-4 Receptor Mutations Can Be Treated with a Glucagon-like Peptide-1 Receptor Agonist

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Interleukin-6 Delays Gastric Emptying in Humans with Direct Effects on Glycemic Control

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Functional brown adipose tissue and sympathetic activity after cold exposure in humans with type 1 narcolepsy

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Apolipoprotein M in patients with chronic kidney disease

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Site-specific O-glycosylation of members of the low-density lipoprotein receptor superfamily enhances ligand interactions

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. The Apolipoprotein M/S1P Axis Controls Triglyceride Metabolism and Brown Fat Activity

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. ApoB and apoM - New aspects of lipoprotein biology in uremia-induced atherosclerosis

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Sumeet A Khetarpal
  • Katrine T Schjoldager
  • Christina Christoffersen
  • Avanthi Raghavan
  • Andrew C Edmondson
  • Heiko M Reutter
  • Bouhouche Ahmed
  • Reda Ouazzani
  • Gina M Peloso
  • Cecilia Vitali
  • Wei Zhao
  • Amritha Varshini Hanasoge Somasundara
  • John S Millar
  • YoSon Park
  • Gayani Fernando
  • Valentin Livanov
  • Seungbum Choi
  • Eric Noé
  • Pritesh Patel
  • Siew Peng Ho
  • Todd G Kirchgessner
  • Hans H Wandall
  • Lars Hansen
  • Eric P Bennett
  • Sergey Y Vakhrushev
  • Danish Saleheen
  • Sekar Kathiresan
  • Christopher D Brown
  • Rami Abou Jamra
  • Eric LeGuern
  • Henrik Clausen
  • Daniel J Rader
  • Myocardial Infarction Exome Sequencing Study
View graph of relations

Human genetics studies have implicated GALNT2, encoding GalNAc-T2, as a regulator of high-density lipoprotein cholesterol (HDL-C) metabolism, but the mechanisms relating GALNT2 to HDL-C remain unclear. We investigated the impact of homozygous GALNT2 deficiency on HDL-C in humans and mammalian models. We identified two humans homozygous for loss-of-function mutations in GALNT2 who demonstrated low HDL-C. We also found that GALNT2 loss of function in mice, rats, and nonhuman primates decreased HDL-C. O-glycoproteomics studies of a human GALNT2-deficient subject validated ANGPTL3 and ApoC-III as GalNAc-T2 targets. Additional glycoproteomics in rodents identified targets influencing HDL-C, including phospholipid transfer protein (PLTP). GALNT2 deficiency reduced plasma PLTP activity in humans and rodents, and in mice this was rescued by reconstitution of hepatic Galnt2. We also found that GALNT2 GWAS SNPs associated with reduced HDL-C also correlate with lower hepatic GALNT2 expression. These results posit GALNT2 as a direct modulator of HDL metabolism across mammals.

Original languageEnglish
JournalCell Metabolism
Volume24
Issue number2
Pages (from-to)234-45
Number of pages12
ISSN1550-4131
DOIs
Publication statusPublished - 9 Aug 2016

    Research areas

  • Journal Article

ID: 49288876