Battle of the bulge: the yin and yang of vascular endothelial growth factor in obesity.

1034 Material force moves and flows in all directions and in all manners. Its two elements unite and give rise to the concrete. Thus the multiplicity of things and human beings is produced. In their ceaseless successions the two elements of yin and yang constitute the great principles of the universe. 1 Y in and Yang are fundamental concepts of Chinese philosophy ; 2 complementary yet competing forces that together influence nature and the elements. Yin is the darker, more negative side; Yang is the brighter, more positive side. The concept of yin and yang exists throughout medicine, 2 and certainly applies to the biology of the vascular endothelial growth factor (VEGF) family. The VEGF family consists of 5 ligands (VEGF-A through-D and placental growth factor). The most-studied VEGF ligand, VEGF-A, is encoded on chromosome 6; at least 12 splice iso-forms have been described previously. Two distinct families of VEGF-A variants are created by alternate splice-site selection, whereby proximal splice selection in exon 8 results in mRNA encoding 7 proangiogenic VEGF-A isoforms, VEGF xxx (where xxx is the number of amino acids), and distal splice selection results in mRNA encoding at least 5 complementary antiangiogenic VEGF-A isoforms, VEGF xxx b (Figure). 3 First described in normal kidney (and down-regulated in renal cell carcinoma) in 2002, 4 the most well-characterized antiangiogenic VEGF-A isoform is VEGF-A 165 b. VEGF 165 b has a 6-amino-acid difference on exon 8 in comparison with VEGF-A 165 and acts as a competitive antagonist against VEGF-A 165 by binding to the VEGF receptor-2 but not stimulating full tyrosine phosphorylation because of a lack of binding to neuropilin-1 (a VEGF coreceptor), preventing receptor activation and its downstream effects. 5 A complex interplay exists between VEGF-A 165 and VEGF-A 165 b in several disease states, where a switch between proangiogenic VEGF-A 165 and antiangiogenic VEGF-A 165 b may lead to disease manifestation and progression. This interrelationship between VEGF-A isoforms has been studied in cancers, including renal cell car-cinoma 4 and prostate cancer, 6 and in proliferative retinopathy, 7 where the downregulation of VEGF-A 165 b shifts the balance in favor of proangiogenic VEGF-A 165 resulting in pathological angiogenesis. Thus, in these diseases, VEGF-A 165 b acts as the yang to the yin of VEGF-A 165. So how does the concept of yin and yang apply to VEGF in obesity? White and brown adipose tissues are highly vas-cularized, and as …