To further prove T-cadherin's partnership with adiponectin in cardiac protection, the researchers attempted a rescue experiment. It was known that administering adiponectin to adiponectin-deficient mice reverses stress-induced heart damage. If T-cadherin were indeed necessary for mediating adiponectin-induced cardioprotection, then this rescue should not work in T-cadherin-deficient mice. Therefore, the researchers first had to generate a mouse model that lacks both the hormone and the receptor. Indeed, adding adiponectin to the double mutant mice did not rescue the stress-damaged hearts, underscoring the importance of T-cadherin for adiponectin functions in the heart.

How do adiponectin and T-cadherin collaborate to promote healthy hearts? Adiponectin is known to activate a cascade of molecular events converging on a protein called AMP-activated protein kinase (AMPK), which in turn regulates energy usage in the cell. This study showed that T-cadherin is required for adiponectin-induced AMPK activity.

According to Dr. Ranscht, the next steps will be to test if T-cadherin is necessary for adiponectin's other beneficial functions in metabolism and inflammation, and to identify the pathways connecting T-cadherin to AMPK activation in the heart. "Our work shows that T-cadherin is necessary for adiponectin functions, but we still don't know how T-cadherin transmits the adiponectin-binding signal into the cell. We are now searching for proteins that might functionally associate with T-cadherin and thus form the molecular link between T-cadherin and AMPK."

Source: Sanford-Burnham Medical Research Institute