Over the last few decades obesity has reached epidemic proportions in children as well as in adults. Obesity is associated with increased risk of insulin resistance, dyslipidemia, elevated blood pressure, and inflammation, all features of metabolic syndrome (MetS), which is linked to an increased risk of type 2 diabetes, cardiovascular disease (CVD), and non-alcoholic fatty liver disease (NAFLD). NAFLD implies infiltration of hepatocytes with lipids, with a spectrum ranging from simple steatosis to steatohepatitis (NASH), progressive to cirrhosis. NAFLD is presently considered a hepatic manifestation of the MetS, with a key role in the pathogenetic mechanisms of cardiometabolic complications.
Osteoprotegerin (OPG) is a member of the tumor necrosis factor (TNF) receptor superfamily, which can function as a decoy receptor by binding to receptor activator of NF- kB (RANK) ligand (RANKL) and competitively inhibiting the interaction between RANKL and RANK. The OPG/RANK/RANKL axis, a key regulatory system in bone homeostasis, also participate in the pathogenesis of atherosclerosis and cardiovascular diseases by amplifying the adverse effects of inflammation and several traditional risk factors such as insulin resistance, hyperlipidemia, endothelial dysfunction, diabetes mellitus, and hypertension. Clinical data have showed that serum OPG levels are associated with hypertension and left ventricular hypertrophy in the general population, with vascular calcification and endothelial dysfunction in subjects with and without diabetes, with severity of liver damage in patients with chronic hepatitis C. In addition, plasma sRANKL level as well as OPG gene polymorphism, especially for rs2073617 T>C and rs2073618 G>C polymorphisms, have been closely related to an increased risk of CVD. In view of these findings, there is significant interest in developing OPG/RANK/RANKL as biomarkers and probably therapeutic targets for cardiovascular and metabolic diseases.
