Dietary Control of MGAT-Dependent N -Glycan Branching: Implications for Metabolic Homeostasis

Abstract

Mannosyl-glycoprotein N-acetylglucosaminyltransferases (MGATs) build branched complex N-glycans that shape the cell–surface glycoproteome and tune lectin–glycan control of receptor stability, endocytosis, and signaling. Although MGAT-dependent branching is well studied in cancer and immunity, its role as a diet-responsive regulator of metabolic homeostasis remains underexplored. Here, we review tissue-specific MGATs expression and metabolic roles in the pancreas, liver, adipose tissue, and skeletal muscle. We discuss how macronutrients, N-acetylglucosamine (GlcNAc) availability, and dietary bioactives, including geniposide, anthocyanins, resveratrol, curcuminoids, and vitamin D, reshape MGATs expression, branching capacity, and glycoprotein function. Current evidence positions MGAT-dependent N-glycan branching as a nutrient-sensitive interface linking diet to receptor signaling and metabolic adaptation. However, most data remain preclinical. Integrating controlled nutrition studies with glycomics and glycoproteomics will be essential to define its translational potential in precision nutrition and metabolic disease prevention.