Session: SAT 723-745-Lipids: Fatty Liver Disease & Lipodystrophies
Poster Board SAT-730
Methods We fed C57BL/6 male mice with a western diet (WD) (high fat and fructose) for 16 weeks and measured INS resistance (HOMA-IR), cardiac diastolic dysfunction (echocardiography), plasma alanine amino transaminase (ALT) levels, hepatic triglycerides, and plasma DPP-4 activity. We further investigated the effect of the DPP-4 inhibitor MK0626 on these parameters in mice on a WD.
Results Compared to mice on a regular chow diet, both INS resistance and diastolic dysfunction were present after 8 weeks on a WD. After 16 weeks of WD, there was a progression in the level of diastolic dysfunction which was accompanied by progressive increases in liver and body weight. The increase in liver weight was accompanied by an increase in plasma DPP-4 activity, hepatic triglycerides, and plasma ALT levels. DPP-4 inhibition treatment begun concurrently with the WD (4weeks of age) substantially reduced plasma DPP-4 activity and improved INS resistance. This was accompanied by improvement in diastolic dysfunction, serum ALT, hepatic triglyceride levels, and plasma DPP-4 activity and levels.
Conclusion We have developed a clinically translational mouse model (WD) of obesity and INS resistance which is accompanied by NAFLD and cardiac diastolic dysfunction which is improved by administration of a DPP-4 inhibitor.
Disclosure: RN: Principal Investigator, Merck & Co.. JRS: Advisory Group Member, Merck & Co.. Nothing to Disclose: AA, ATW, VD
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