Poster Topical Area: Energy and Macronutrient Metabolism
Location: Hall D
Poster Board Number: 397
Objectives: For a long time vasopressin was has been thought to be just a hormone involved in water retention and urinary concentration. However, it has recently been postulated that it also promotes extra renal effects including the storage of fat as a source of metabolic water. We and others have shown that fructose, a heavily used sugar either as sucrose or high fructose corn syrup,induces important features of metabolic syndrome including obesity, fatty liver and insulin resistance. Recently, it has also been found that fructose stimulate vasopressin release thus leading us to the hypothesis that in metabolic syndrome, chronic fructose ingestion might mediate its metabolic effects by activating vasopressin-dependent pathways.
Methods: Male C57Bl/6 Wild Type (WT), Vasopressin 1a receptor Knockout (V1aKO), and Vasopressin 1b receptor Knockout (V1bKO) were maintained in either regualr water or 15% fructose water ad libitum for 30 weeks and features of metabolic syndrome characterized. We also analyzed copeptin levels, a surrogate for vasopressin, in WT, V1aKO, V1bKO, fructokinase A knockout (KHK-A KO), and fructokinase A/C knockout (KHK-A/C KO) on both water and 15% fructose water for 30 weeks.
Results: Chronic fructose exposure resulted in significant elevation of plasma copeptin in all groups. However, despite similalry higher plasma vasopressin levels, V1bKO mice demonstrated significant protection against fructose-induced weight gain, steatohepatitis, insulin resistance, and hyperleptinemia compared to wild type animals. In contrast, V1aKO mice showed not only any sign of protection against fructose but instead, a tendency for a worse metabolic phenotype in response to fructose. Furthermore, our data suggests that the mechanism whereby the blockade of the V1b receptor results in significant protection against fructose-induced metabolic syndrome is mediated by the down-regulation of fructokinase in the liver thus leading to reduced dietary fructose metabolism.
Conclusion: To our knowledge, this is the first study to show that vasopressin is elevated in mice chronically exposed to fructose where it plays an important deleterious role in fructose-induced metabolic syndrome by activating an specific receptor V1b.
Associate Professor of Medicine
University of Colorado AMC