Retinol binding protein 4

Retinol Binding Protein 4 belongs to the lipocalin family and is classified as an adipocytokine. It is encoded by the RBP4 gene, which is located on chromosome 10q23.33.

The RBP4 protein is the specific carrier for retinol (vitamin A alcohol) in the blood (Peterson PA 1971). It transports retinol from the liver depots to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin, which prevents its loss by filtration through the renal glomeruli. Transfers the bound all-trans-retinol to STRA6, which then facilitates retinol transport across the cell membrane (Berry DC et al. 2012).

As an active endocrine organ, adipose tissue secretes many adipokines and cytokines. These biomolecules, known as adipocytokines, play an important role in regulating energy homeostasis and metabolism throughout the body by influencing and altering the function of target tissues. Retinol-binding protein 4 (RBP4) has been linked to systemic insulin resistance, dyslipidemia, type 2 diabetes and other metabolic diseases (Nono Nankam PA et al. 2021).

There is ample evidence that both retinoids and retinol-binding protein 4 (RBP4) contribute to the development of liver disease. Since adipocyte-specific hRBP4 mice exhibit increased expression of tumor necrosis factor-α and leptin as well as "crown-like structures" in adipose tissue, it is hypothesized that adipose tissue undergoes RBP4-induced inflammation that stimulates increased lipolysis in adipocytes (Lee SA et al. 2016)

Circulating RBP4 is not related to the amount of fat in the classical depots or in the ectopic depots in the muscles. However, it correlates positively with liver fat. In addition, metabolic parameters confirm the close relationship between circulating RBP4 and liver fat and presumably also the insulin resistance of the liver.

A lack of vitamin A blocks the secretion of the binding protein post-translationally and leads to an impaired supply to the epidermal cells.

Adipokines, including retinol-binding protein 4 (RBP-4), play an important role in psoriasis vulgaris. The summarized data of several studies indicate that RBP-4 levels were significantly higher in patients. Systemic treatment can lower these levels. RBP-4 could thus serve as an important indicator for the diagnosis, efficacy evaluation and monitoring of comorbidities in these patients (Gao G et al. 2023).

1. Berry DC et al. (2012) Cross talk between signaling and vitamin A transport by the retinol-binding protein receptor STRA6. Mol Cell Biol 32:3164-3175.
2. Gao G et al. (2023) Association between retinol binding protein-4 and psoriasis vulgaris: a systematic review and meta-analysis. Front Med (Lausanne) 10:1208969.
3. Lee SA et al. (2016) Adipocyte-specific overexpression of retinol-binding protein 4 causes hepatic steatosis in mice. Hepatology 64:1534-1546.
4. Nono Nankam PA et al. (2021) Retinol-binding protein 4 in obesity and metabolic dysfunctions. Mol Cell Endocrinol 531:111312.
5. Peterson PA (1971). Studies on the interaction between prealbumin, retinol-binding protein, and vitamin A. J Biol Chem 246:44-49.
6. Romeo S et al. (2016) Regulation of retinol-binding protein 4 and retinol metabolism in fatty liver disease. Hepatology 64:1414-1416.
7. Stefan N et al. (2007) High circulating retinol-binding protein 4 is associated with elevated liver fat but not with total, subcutaneous, visceral, or intramyocellular fat in humans. Diabetes Care 30:1173-1178.