(Left side, orange lines) Fructose stimulates both the expression of fructokinase (KHK) and the induction of the V1bR in the liver. Fructose metabolism in both liver and hypothalamus stimulates the production and secretion of AVP. The actions of AVP on hepatic V1bR potentiate the metabolic effects of fructose on the expression of KHK and lipogenic enzymes FAS and ACC. As a result, AVP and fructose promote fatty liver, adiposity, and body weight gain during the development and progression of metabolic syndrome. (Right side, blue lines) Hydration and other strategies directed to lower circulating AVP levels would decrease the hepatic expression of both V1bR and KHK in response to fructose. As a consequence, less fructose would be metabolized into fat, thus limiting the progression of metabolic syndrome. V1bR, vasopressin 1b receptor; AVP, vasopressin; KHK, ketohexokinase; FAS, fatty acid synthase; ACC, acetyl-CoA carboxylase.