Associated with major modification in JH signaling. Our study sets the stage for unveiling the molecular underpinnings of these evolutionary modifications in JH signaling pathways. The modification in JH signaling along the evolution of advanced sociality may not be unique to honey bees because there is evidence for an association between JH levels and division of labor rather than ovarian state also in advance eusocial ants and wasps in which eusociality evolved independently from bees. Haptoglobin is an acute-phase plasma glycoprotein produced mainly by hepatocytes and adipocytes, and is the major hemoglobin binding serum protein in several mammals. The concentrations of Hp in the plasma are high, ranging from 0.3 mg/ml to 3 mg/ml, producing an Hp:Hb molar ratio of 400. By forming a complex with Hb, Hp prevents both iron loss and kidney damage during hemolysis. The Hp-Hb complex is transported to the liver and other tissues to be degraded by HpHb scavenger receptors, such as the CD163 receptor present on macrophages and liver Kupfer cells. An important aspect of Hb scavenging by Hp is the reduction in Oxidative Stress. Indeed extracorpuscular Hb can initiate a free radical reaction by releasing heme iron, which acts as a potent Fenton reagent. This reaction results in the production of Reactive Oxygen Species and consequent oxidative damage to tissues. Hp binding to Hb prevents this cascade by shielding the heme iron from its aqueous surrounding. A prominent aspect of mice lacking Hp is the oxidative damage suffered by their kidney in the presence of acute hemolysis provoked by phenylhydrazine injection. In the first comprehensive description of this mouse model Baumann and colleagues state that the most important physiological function of the strong Hb-Hp binding is to inhibit Hb-stimulated lipid peroxidation. Indeed these mice show higher levels of the systemic OS indicators malonaldehyde and 4-hydroxy- 2-nonenal. Hp is part of the acute phase response to inflammation for which is considered a marker in the clinical practice. Hp is also specifically induced in the white adipose tissue upon obesity, this being LY2109761 TGF-beta inhibitor reflected in the increased plasma levels of the glycoprotein found in obese subjects. The induction of Hp seen in chronic conditions typically associated to enhanced OS might be a mechanism to prevent an excessive damage caused by free radicals. Noteworthy the two common alleles for Hp present in humans possess different properties, with the protein encoded by Hp 1-1 providing superior antioxidant protection compared with that encoded by Hp 2-2. Diabetic individuals with Hp 2-2 have been reported to be more prone to develop nephropathy, retinopathy, and cardiovascular disease than those with the Hp 2-1 or Hp 1-1 genotypes. If on one side Hp induction in conditions of enhanced OS, as in the adipose tissue of obese subjects, is protective, on the other its proven chemotactic potential for macrophages augments the local inflammatory infiltrate. Indeed Hp absence diminishes local inflammation and enhances insulin sensitivity in the adipose tissue of obese mice and partially protects from obesity associated insulin resistance.