主催: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
会議名: WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
開催地: Kyoto
開催日: 2018/07/01 - 2018/07/06
Background
Obesity as global epidemic contributes greatly to the incidence of cardiovascular disease and strongly related to metabolic disorders. Obesity is caused by an imbalance between energy intake and energy consumption. One strategy to tackle obesity is to pharmacologically convert the energy storing white adipocyte into the energy-consuming brown adipocyte. Recently, it has been reported that JAK inhibitor induced browning of white adipose tissue (WAT) in vitro; however, this has not been proven in vivo studies. Here, we report the in vivo effects of JAK inhibition on browning of WAT and systemic metabolic homeostasis.
Methods
In this in vivo study, we used C57BL/6 mice given high-fat diet for 4 weeks to mimic obese mice and subsequently divided into 2 groups; JAK inhibitor-treatment group and vehicle-treatment group. The administration of JAK inhibitor drug (Tofacitinib) was performed through an osmotic pump implanted subcutaneously for 8 weeks. At the end of treatment, insulin sensitivity was assessed by insulin tolerance test.
Results
Body weight in JAK inhibitor group showed a tendency toward decrease, though not statistically significant. JAK inhibition significantly improved the insulin sensitivity in mice compared with vehicle-treated group despite the similar body weight. Of note, JAK inhibition induced the browning of both subcutaneous and visceral WAT assessed by increased expression of brown adipocyte markers such as UCP-1 and PRDM16. Adipocyte size was reduced in WAT of JAK inhibitor groups, but chronic inflammation in WAT was not different between the groups.
Conclusion
We revealed that JAK inhibition could induce the browning of WAT and improved the systemic metabolic health in vivo. Though detailed molecular mechanisms remain to be elucidated, our data defined that JAK signaling is an attracting pharmacotherapeutic target for the treatment of obesity and its related metabolic disorders.
