Effect of weight loss and exercise on angiogenic factors in the circulation and in adipose tissue in obese subjects

Background: Vascular growth is a prerequisite for adipose tissue (AT) development and expansion. Some AT cytokines and hormones have effects on vascular development, like vascular endothelial growth factor (VEGF-A), angiopoietin (ANG-1), ANG-2 and angiopoietin-like protein-4 (ANGPTL-4). Methods: In this study, the independent and combined effects of diet-induced weight loss and exercise on AT gene expression and proteins levels of those angiogenic factors were investigated. Seventy-nine obese males and females were randomized to: 1. Exercise-only (EXO; 12-weeks exercise without diet-restriction), 2. Hypocaloric diet (DIO; 8-weeks very low energy diet (VLED) + 4-weeks weight maintenance diet) and 3. Hypocaloric diet and exercise (DEX; 8-weeks VLED + 4-weeks weight maintenance diet combined with exercise throughout the 12 weeks). Blood samples and fat biopsies were taken before and after the intervention. Results: Weight loss was 3.5 kg in the EXO group and 12.3 kg in the DIO and DEX groups. VEGF-A protein was non-significantly reduced in the weight loss groups. ANG-1 protein levels were significantly reduced 22-25% after all three interventions (P < 0.01). The ANG-1/ANG-2 ratio was also decreased in all three groups (P < 0.05) by 27-38%. ANGPTL-4 was increased in the EXO group (15%, P < 0.05) and 9% (P < 0.05) in the DIO group. VEGF-A, ANG-1, and ANGPTL-4 were all expressed in human AT, but only ANGPTL-4 was influenced by the interventions. Conclusions: Our data show that serum VEGF-A, ANG-1, ANG-2, and ANGPTL-4 levels are influenced by weight changes, indicating the involvement of these factors in the obese state. Moreover, it was found that weight loss generally was associated with a reduced angiogenic activity in the circulation.