Retinol binding protein 4 (RBP4)

Retinol binding protein 4, also known as RBP4, is a transporter protein for retinol (vitamin A alcohol) in the bloodstream.

It is primarily synthesized in the liver and secreted into the bloodstream, where it binds to retinol and carries it to various tissues in the body.

Retinol is an essential nutrient that plays a crucial role in vision, growth, development, and maintenance of healthy skin and mucous membranes. 

It is also important for the immune system and reproductive system.

RBP4 acts as a carrier protein for retinol because retinol is not very soluble in water and needs to be transported in the bloodstream bound to a protein. 

RBP4 binds to retinol, forming a complex that circulates in the blood and delivers retinol to target tissues.

It has a role in the context of insulin resistance and type 2 diabetes, as elevated levels of RBP4 have been found in individuals with these conditions. 

RBP4 has also been associated with obesity, metabolic syndrome, and cardiovascular disease.

A major factor in RBP4  induced insulin resistance is its increase in adipose tissue inflammation.

RBP4 has a molecular weight of approximately 21 kDa and is encoded by the RBP4 gene.

It is mainly, though not exclusively, synthesized in the liver and circulates in the bloodstream as a hepatokine bound to retinol in a complex with transthyretin. 

RBP4 has been a drug target for ophthalmology and metabolic disease research.

Belongs  to the lipocalin family and is the specific carrier for retinol (vitamin A) in the blood. 

It delivers retinol from the liver stores to the peripheral tissues. 

In plasma, the RBP-retinol complex interacts with transthyretin, preventing its loss by filtration through the kidney glomeruli. 

A deficiency of vitamin A blocks secretion of the binding protein posttranslationally and results in defective delivery and supply to the epidermal cells.

Two molecules of RBP4 bound to retinol is complexed with four molecules of TTR.

The RBP4-retinol complex then binds transthyretin in circulation to prevent renal filtration of RBP4.

TTR and RBP4 bind in a 1 to 1 stoichiometry in drum, to form a complex with a total molecular weight of approximately 80,000 Daltons.

RBP4 is the sole carrier for retinol, which is an essential nutrient for the visual cycle. 

Animal studies using RBP4-antagonists showed that lowering RBP4 can lead to reduction in the accumulation of lipofuscin that leads to vision loss in eye diseases like Stargardt’s disease and macular degeneration.

A clinical study in age-related macular degeneration (AMD) was conducted using Fenretinide: study showed trends in reducing lesion growth rate in AMD and rate of conversion from early stage AMD (dry AMD) to late stage AMD (wet AMD) without serious side effects.

RBP4 it is an adipokine that contributes diabetes and attracts macrophages to the fat tissue, causes local inflammation, and leads to insulin resistance.

Mutations in the RBP4 gene are linked to a form of autosomal dominant microphthalmia, anophthalmia, and coloboma (MAC) disease.

A fetus inherits a mutated copy of the RBP4 gene from its mother, but not from its father. 

During pregnancy the mutated gene product, retinol binding protein (RBP), has negative effects in transferring vitamin A from maternal liver storage sites to the placenta, and then again on the fetal circulation side when delivering vitamin A from the placenta to developing fetal tissues, most notably the developing eye. 

This effect does not exist when the mutant RBP4 gene is inherited from the father. 

The RBP4 expression in adipocytes is altered in response to changes in adipocyte GLUT4 expression.

RBP4 levels are elevated in many insulin resistant states, including obesity, type two diabetes, polycystic ovary syndrome, HIV associated lipodystrophy, as well as in patients with dyslipidemia, coronary artery disease and hypertension.

There is a strong inverse correlation between serum RBP4 levels and insulin sensitivity.

RBPP4  increases adipose tissue inflammation.

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