The role of adipocyte-derived proteases on differential processing of chemerin in obesity

Approximately twenty-three percent of the adult Canadians are obese. Characterized by excess fat tissue and inflammation, obesity increases the likelihood for type II diabetes, stroke and cardiac diseases. Hence, obesity places a toll on individual health, the health care system and the economy. Fat tissue releases hormone-like molecules called adipokines that affects metabolism and inflammation. We discovered an adipokine chemerin that is involved in: the development of fat cells, fat metabolism and inflammation. Chemerin is released from cells as an inactive molecule (prochemerin). At sites of tissue injury, enzymes called proteases convert (process) prochemerin to active (functional) chemerin. Other proteases can degrade chemerin and end the action of the functional protein. Although human studies have suggested that chemerin may be involved with the development of obesity-related diseases, little is known about how fat cells regulate the production of chemerin. While the current belief is that immune cells process chemerin, we identified that fat cells produces active chemerin and therefore, must produce the enzymes involved with processing chemerin. We further identified that under inflammatory conditions fat cells may process chemerin to a form that has very high biological activity. Our research will identify if adipocyte proteases are altered in obesity and if the alteration in proteases increases the amount of active chemerin produced. Understanding how fat cells process prochemerin or chemerin may serve as the basis for blocking chemerin function. This could have health benefits by reducing the inflammatory or insulin resistance effects of chemerin in human diseases, notably obesity, which is a major cause of disability and premature death.