A lower dose of liraglutide in patients with metabolic syndrome reduces epicardial adipose tissue, increases aerobic capacity and activates AMPK levels in circulating mononuclear cells.

Background There is a substantial body of evidence supporting the efficacy of GLP-1 receptor agonists in the treatment of patients with diabetes mellitus, obesity, metabolic syndrome (MS) and heart failure with preserved ejection fraction. However, despite the fact that they are currently recommended at standard doses for patients with obesity and MS, the protective cardiovascular mechanisms beyond weight reduction are less well understood. We hypothesize here that a lower dose of a GLP-1 receptor agonist could increase aerobic capacity, reduce pericardial fat and activate AMP-activated protein kinase (AMPK) in patients with MS. AMP-activated protein kinase (AMPK). AMPK is an enzyme that senses energy levels and modulates the body's shift from an anabolic to a catabolic state, where energy is expended and molecules are broken down. Activated AMPK also improves insulin sensitivity, triggers autophagy and reduces inflammation. Purpose To evaluate the effect of a lower dose of the GLP-1 receptor agonist liraglutide on aerobic capacity, epicardial fat thickness (EFT) and phosphorylated AMPK in patients with MS. Methods Prospective pilot open study in 23 consecutive patients with MS (age 54.9 ± 14 years, 12 women, body mass index 33.6 ± 0.61 kg/m²). Liraglutide was administered daily for 12 weeks at a maximal dose of 1.8 mg sbc/day. Besides, a reduction in carbohydrate consumption and daily moderate aerobic exercise were prescribed. EFT was measured by 2D echocardiogram using conventional methodology with good reproducibility and low intra and interobserver variability. Duration of cardiopulmonary exercise test and peak oxygen consumption were also dtermined with a gas exchange analysis system in a treadmill protocol. AMPK ratio (phosphorylated/total, p/t) in peripheral mononuclear blood cells (PBMCs) was determined by Western Blot. Results (mean ± SD). After 12 weeks of treatment with liraglutide, patients with MS showed body weight reduction (from 92.7 ± 14.4 kg to 86.6 ± 13.3 kg, p<0.001) and a significant reduction in EFT (from 5.08 ± 1.15 to 4.18 ± 0.86 mm). Longer exercise duration (from 507 ± 90 to 563 ± 93 secs, p<0.001) and higher peak VO2 (from 19.6 ± 2.0 to 21 ± 2.4 mL/kg/min, p<0.01) were also observed with liraglutide. Furthermore, phosphorylated/total AMPK p/t ratio in PMBCs was increased from 0.84 ± 0.56 to 1.52 ± 1.55, p<0.05. Conclusions A lower dose of liraglutide reduced body weight, improved aerobic capacity and reduced EFT in patients with MS in this pilot study. Furthermore, significant AMPK activation in peripheral blood mononuclear cells was also observed. It is possible that AMPK activation could be one of the cardio-metabolic protective mechanisms of GLP-1 receptor agonists.