Figure 3. Semaglutide attenuates glycemic excursion and levels of circulating cholesterol, triglycerides, and cytokines in Glp1r^Tie2+/+ and Glp1r^Tie2–/– mice.

PCSK9-treated HFHC diet–fed mice were tested for blood glucose at weeks 12–13 of the 18-week PCSK9+HFHC diet protocol, with daily vehicle (Veh) or semaglutide (Sema; 10 μg/kg) administration. Mice were fasted for 5 hours followed by administration of 1.5 g/kg glucose for an oral glucose tolerance test (OGTT). (A) The area under the curve (AUC) was calculated to compare Veh with Sema treatment in Glp1r^Tie2+/+ and Glp1r^Tie2–/– mice. At weeks 16–17 of the treatment protocol, mice were fasted for 5 hours and blood was collected for fast protein lipid chromatography: (B) triglyceride and (C) cholesterol levels in VLDL, LDL,and HDL fractions were measured. (D) Cytokines were measured in plasma obtained from terminal bleeds at the end of the experiment (n = 6–14). Data are presented as mean ± SD, with individual data points shown. *P < 0.05 for Sema effect, 2-way ANOVA multiple-comparison test.