The Emerging Role of Sialic Acids in Obesity and Diabetes: Molecular Mechanisms and Therapeutic Perspectives

TL;DR

This review explores how sialic acids and related molecules influence obesity and diabetes, highlighting their roles in insulin signaling and inflammation.

Contribution

The paper provides a comprehensive overview of the sialic-acid axis in metabolic diseases and identifies gaps for future research.

Findings

Sialic-acid levels and related enzymes are dysregulated in obesity and diabetes.

Changes in sialic acids affect insulin signaling and inflammatory responses.

Controversies remain due to differences in glycan structures and tissue-specific roles.

Abstract

Sialic acids are terminal monosaccharides that cap glycans on glycoconjugates. Accumulating clinical and experimental evidence shows that obesity, insulin resistance, and diabetes are accompanied by changes in sialic-acid levels. In these conditions, the sialic-acid axis is also broadly remodeled: writers (sialyltransferases), erasers (neuraminidases), and readers (Siglecs) are dysregulated across adipose tissue, liver, pancreas, endothelium, and blood, shifting insulin signaling and inflammatory tone. This review summarizes relevant studies from the perspectives of disease clinical indicators, molecular mechanisms, and interventions targeting sialic acid. Taken together, these results confirm that sialic acids and related molecules play important roles in multiple metabolic diseases; however, controversies remain due to differences in glycan structure, isoforms, and tissue specificity, particularly regarding the precise roles of neuraminidases. Future studies should build on advanced, standardized glycomic and glycoproteomic measures to define molecule- and tissue-specific roles of sialic acids in metabolic disease, enabling reliable biomarkers and guiding targeted therapy.

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