Targeting CD44-Hyaluronic Acid Signalling in Obesity Treatment: Insights from Small Molecules and Nanobioconjugates

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Obesity is a complex metabolic disorder associated with chronic low-grade inflammation, insulin resistance, and heightened risk of comorbidities such as cardiovascular diseases and type 2 diabetes mellitus (T2DM). The Cluster of Differentiation 44 (CD44), a transmembrane glycoprotein, interacts with hyaluronic acid (HA), a major extracellular matrix (ECM) component, to regulate adipogenesis, immune cell infiltration, and metabolic dysfunction. Dysregulation of the CD44-HA signalling axis promotes adipose tissue hypertrophy, macrophage infiltration, and activation of pro-inflammatory pathways, including nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs), which further aggravate metabolic disturbances. This review provides a comprehensive analysis of CD44-HA signalling in the pathophysiology of obesity and evaluates therapeutic strategies targeting this axis. Small-molecule inhibitors, such as CD44 antagonists and hyaluronan biosynthesis modulators (eg, 4-methylumbelliferone), offer advantages in synthesis, bioavailability, and cost-effectiveness, but face challenges related to limited specificity, systemic toxicity, and potential resistance. In contrast, Nanobioconjugates engineered nanoparticles conjugated with biomolecules such as HA enable targeted delivery to CD44-overexpressing adipose tissues, enhance therapeutic efficacy, prolong drug release, an

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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