New Key Publication: A novel role for GalNAc-T2 dependent glycosylation in energy homeostasis

Highlights

• Variation the GALNT2 gene locus is associated with adiposity and BMI.
• GalNac-T2 plays an important and dynamic role in whole-body energy homeostasis.
• The insulin receptor is a novel substrate of GalNAc-T2.
• Tissue-specific models are required to dissect local roles of GalNac-T2-mediated O-linked glycosylation.

GALNT2, encoding polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2), was initially discovered as a regulator of high-density lipoprotein metabolism. GalNAc-T2 is known to exert these effects through post-translational modification, i.e., O-linked glycosylation of secreted proteins with established roles in plasma lipid metabolism. More recently it has become clear that loss of GALNT2 in rodents, cattle, nonhuman primates and humans should be regarded as a novel congenital disorder of glycosylation which affects development and body weight. The role of GALNT2 in metabolic abnormalities other than plasma lipids, including insulin sensitivity and energy homeostasis, is poorly understood. Taken together, this study identifies a novel role for GALNT2 in energy homeostasis and our findings suggest that the local effects of GalNAc-T2 are mediated through posttranslational modification of the insulin receptor.

Authors:

• Cristy R.C. Verzijl
• Federico Oldoni
• Natalia Loaiza
• Justina C. Wolters
• Antoine Rimbert
• E. Tian
• Weiming Yang
• Dicky Struik
• Marieke Smit
• Niels J. Kloosterhuis
• Amy J. Fernandez
• Nadine L. Samara
• Kelly G. Ten Hagen
• Kruti Dalal
• Aliona Chernish
• Peggy McCluggage
• Lawrence A.Tabak
• Johan W. Jonker
• Jan Albert Kuivenhoven

The paper in Molecular Metabolism : https://www.sciencedirect.com/science/article/pii/S2212877822000412