745-P: Lipidomics Studies on Brown Adipose Tissue by Exercise and Liraglutide in db/db Mice

Background: Brown adipose tissue (BAT) is characterized by regulating whole body energy expenditure, mediating glucose and lipid metabolism. Exercise is one of the favorable lifestyle interventions in against hyperglycemia, and liraglutide is also an ideal therapy in decreasing blood glucose into the normal range and regulating lipid metabolism. But how and whether exercise and liraglutide have an effect on BAT for mediating glucose metabolism are unknown.

Method: Male leptin receptor deficient db/db and age-matched C57BL/6 control mice were used at 6 weeks of age, db/db mice were subjected either to sedentary or exercise training (run on the treadmill, 5.2 m/minutes, 5 days per week) with or without liraglutide (200 ug/kg, twice one day, subcutaneous injection) for 8 weeks. Mice were monitored weekly for blood glucose and body weight. For glucose test, mice were fasted for 8 hours and blood glucose were collected at 0, 15, 30, 60, 90, and 120 minutes. Plasma were collected in heparinized tubes for insulin, triglyceride and cholesterol analysis, then BAT were collected for targeted lipidomics studies (including phosphatidylcholines, phosphatidyl ethanolamine, ceramides and sphingolipids) in a surveyor HPLC system (HPLC-MS/MS).

Results: Moderate exercise training and liraglutide treatment significantly lowered blood glucose in db/db mice, only exercise + liraglutide group showed down-regulated triglyceride level. BAT targeted lipidomics results showed that 7 Lysophosphatidyl choline, 4 phosphatidylcholines and 1 sphingolipids fatty acids did not expression in db/db mice than control. Surprisingly, compared with db/db mice, exercise training and liraglutide did not significantly change in any fatty acid expressions.

Conclusions: In this study, exercise training and liraglutide treatment exert a significant role in lowering blood glucose, but they may have no effective regulation of fatty acids metabolism on BAT.