GLP-1 receptor agonism reduces hepatic VLDL-TG and VLDL-apoB production without affecting VLDL particle composition.

<p><i>E3L</i> mice were fed a HFD for 22 weeks. The last 4 weeks, mice were treated with either vehicle (HFD control), CNTO3649 (1.0 or 3.0 mg/kg/day) or exendin-4 (15 or 50 μg/kg/day). As a control for HFD feeding, an additional group of mice fed a chow diet was included that received vehicle (chow control). After 7 h fasting, mice were injected with Tran³⁵S label (t = −30 min) and Triton WR-1339 (t = 0 min). Blood was drawn at the indicated time points and plasma TG concentrations were determined (A, B). VLDL-TG production rate was calculated as µmol/h from the slopes of the TG-time curves of the individual mice (C). At t = 120 min, mice were exsanguinated, and VLDL was isolated by density gradient ultracentrifugation. ³⁵S-activity was determined, and VLDL-apoB production rate was calculated as dpm.h⁻¹ (D). The VLDL-TG production rate to VLDL-apoB production rate ratio was calculated as nmol/dpm (E). The content of triglycerides, cholesterol, phospholipids and protein in VLDL was determined and calculated as % of total mass (F). Values are means ± SEM for at least 6 mice per group. <i>*</i>P<0.05, <i>**</i>P<0.01, <i>***</i>P<0.001 compared to HFD controls. TG: triglycerides; TC: total cholesterol; PL: phospholipids; Pro: protein.