Remodeling of α1-Acid Glycoprotein Glycoforms During Long-Term Calorie Restriction

AGP1 (α-1 acid glycoprotein) is an acute phase immune response protein recently shown to influence leptin receptor activity and body weight regulation. AGP is a highly glycosylated protein, with 45% of its molecular weight made up by glycans, yet little is known about how the latter responds to metabolic interventions or its role in AGPs immunometabolic function. In this pilot study (n = 26), we evaluated the effect of calorie restriction (CR - 2years, 25% CR in non-obese adults) on N-glycosylation of AGP1. AGP1 has 5 glycosylation sites, of which sites IV and V are dominated by highly branched, fucosylated, and sialylated glycans, and inflammatory conditions are associated with reduced branching at sites IV and V and increased fucosylation. With CR (0 month to 24 month, ~12% CR, weight loss of ~8.2 kg), there was increase in branching at sites IV and V (p<0.05, FDR corrected), and increased fucosylation (p<0.05, FDR corrected). Exploratory moderation analyses suggest that highly sialylated site IV glycans and low-branched site I glycans may influence the relationship between CR and leptin (p<0.05). Overall, AGP glycome is largely remodeled with CR, and it is unknown if these are upstream or downstream of immunometabolic changes seen with CR.