Plasma Transthyretin as a Biomarker of Lean Body Mass and Catabolic States

Plasma transthyretin (TTR) is a plasma protein secreted by the liver that circulatesbound to retinol-binding protein 4 (RBP4) and its retinol ligand. TTR is the soleplasma protein that reveals from birth to old age evolutionary patterns that areclosely superimposable to those of lean body mass (LBM) and thus works as the bestsurrogate analyte of LBM. Any alteration in energy-to-protein balance impairs theaccretion of LBM reserves and causes early depression of TTR production. In acuteinflammatory states, cytokines induce urinary leakage of nitrogenous catabolites,deplete LBM stores, and cause an abrupt decrease in TTR and RBP4 concentrations. As aresult, thyroxine and retinol ligands are released in free form, creating a secondfrontline that strengthens that primarily initiated by cytokines. Malnutrition andinflammation thus keep in check TTR and RBP4 secretion by using distinct andunrelated physiologic pathways, but they operate in concert to downregulate LBMstores. The biomarker complex integrates these opposite mechanisms at any time andthereby constitutes an ideally suited tool to determine residual LBM resources stillavailable for metabolic responses, hence predicting outcomes of the most interwovendisease conditions.