Retinol-Binding Protein 4 and Metabolic Dysfunction
Summary
Retinol-binding protein 4 (RBP4) is the principal carrier of vitamin A (retinol) in the circulation and is predominantly synthesised by the liver and by adipocytes. Beyond its classical role in vitamin A homeostasis, RBP4 functions as an adipokine that modulates insulin sensitivity, lipid partitioning and inflammatory responses in peripheral tissues. Elevations in circulating RBP4 have been linked to insulin resistance, dyslipidaemia, non-alcoholic fatty liver disease and cardiovascular risk, suggesting a central role in the pathogenesis of common metabolic disorders. Mechanistically, RBP4 engages its membrane receptor STRA6 to activate downstream JAK2–STAT3 signalling, promoting pro-inflammatory gene expression and impairing insulin-mediated glucose uptake. Independent of retinol transport, RBP4 may also act as a danger-associated molecular pattern (DAMP), triggering innate immune pathways in target cells. The clinical significance of RBP4 is underscored by its potential as a biomarker for early detection of metabolic derangements and as a target for pharmacological intervention, although translational studies have yielded mixed results regarding the efficacy of RBP4-lowering strategies on glycaemic control.
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Retinol-Binding Protein 4 and Metabolic Dysfunction publication trend
The graph below shows the total number of articles in retinol-binding protein 4 and metabolic dysfunction across all publications each year (not limited to Nature Index journals).
Technical terms
Retinol-binding protein 4 (RBP4): A lipocalin family protein that transports retinol in blood and acts as an adipokine influencing metabolic and inflammatory pathways.
Adipokine: A signalling molecule secreted by adipose tissue that modulates systemic energy balance, insulin sensitivity and inflammation.
STRA6: A transmembrane receptor for RBP4 that, upon binding retinol-loaded RBP4, initiates intracellular JAK2–STAT3 signalling cascades.
Danger-associated molecular pattern (DAMP): An endogenous molecule that, when released or presented in non-physiological contexts, activates innate immune receptors and inflammatory responses.
References
- RBP4 promotes denervation‐induced muscle atrophy through STRA6‐dependent pathway. Journal of Cachexia Sarcopenia and Muscle (2024).
- The Hepatokine RBP4 Links Metabolic Diseases to Articular Inflammation. Antioxidants (2024).
- Diagnostic value of retinol-binding protein 4 in diabetic nephropathy: a systematic review and meta-analysis. Frontiers in Endocrinology (2024).
- Biological Functions of RBP4 and Its Relevance for Human Diseases. Frontiers in Physiology (2021).
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