Vitamin A is an essential nutrient involved in vision, growth, cellular differentiation, and immune function. Because vitamin A is fat-soluble, it is chaperoned through the body on carrier proteins. Researchers at the University of Wisconsin-Madison in a study funded by USDA and NIH, discovered that not only was one of the carrier proteins for vitamin A, retinol-binding protein (RBP), elevated in obese individuals compared to leaner controls, but some of it was not attached to retinol, the main circulating form of the vitamin. RBP that is not bound to vitamin A is called apo-RBP by vitamin A scientists. Their study will appear in the October 08 issue of Experimental Biology and Medicine.
The research team led by Sherry Tanumihardjo, an associate professor of Nutritional Sciences, originally was interested in determining the degree of hypervitaminosis A in the cohort for preliminary data on excessive liver storage of the vitamin. Her graduate student, Jordan Mills, was interested in determining the retinol-binding protein concentrations. While the degree of hypervitaminosis A was remarkable at 4% prevalence for the obese cohort, the relationship of retinol to RBP was a more interesting discovery. The retinol to RBP ratio (retinol:RBP) was significantly lower in the obese subjects than nonobese subjects. This was attributable to more RBP circulating in the serum not bound to vitamin A. RBP was strongly associated with vitamin A in both groups, but more so in the nonobese individuals.
"A series of studies in mice and humans revealed a strong relationship between serum RBP and obesity-induced insulin resistance. While some studies validated these original observations of elevated RBP in obesity and insulin resistance in humans, others have not. Often lacking in these publications are data for serum retinol, arguably RBP's most important physiological companion, representing a possible explanation for conflicting results," said Mills. Tanumihardjo added, "Our results further the understanding of the relationship of retinol, RBP, and BMI and suggest that apo-RBP should be evaluated. Retinol:RBP may add new insights and be a better clinical diagnostic for potential insulin resistance than RBP alone." The authors say, "This elevated serum apo-RBP may be adipose-derived and it is unknown whether it is a direct contributor to insulin resistance in obese individuals. Alternatively, apo-RBP from adipose may transport an unidentified ligand that is responsible for mediating insulin signaling." Further research is needed to determine whether apo-RBP is bound to some other compound in circulation. Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said "this interesting study, led by Dr. Tanumihardjo, opens the door to the determination of the role of apo-RBP in insulin resistance in obese individuals. This will be an important issue for those working on type 2 diabetes".