Abstract

Objective: The adipocyte-derived secretory protein adiponectin has been widely studied and shown to have potent insulin-sensitizing, anti-apoptotic and anti-inflammatory properties. While its biosynthesis is well understood, its fate once in circulation is less well established.

Research Design and Methods: Here, we examine the half-life of adiponectin in circulation by tracking fluorescently labeled recombinant adiponectin in the circulation following it to its final destination in the hepatocyte.

Results: Despite its abundant presence in plasma, adiponectin is cleared rapidly with a half-life of about 75 minutes. A more bioactive version carrying a mutation at Cys39 is cleared within minutes. Even though steady state levels of adiponectin differ between male and female mice, we failed to detect any differences in clearance rates, suggesting that differences in plasma are mostly due to differential production rates. In a metabolically challenged state (high fat diet exposure or in an ob/ob background), adiponectin levels are reduced in plasma and clearance is significantly prolonged, reflecting a dramatic drop in adiponectin production levels.

Conclusion: Combined, these results show a surprisingly rapid turnover of adiponectin with multiple fat pads contributing to the plasma levels of adiponectin and clearance mediated primarily by the liver. It is surprising that despite high level production and rapid clearance, plasma levels of adiponectin remain remarkably constant.