Depot-Specific Differences and Insufficient Subcutaneous Adipose Tissue Angiogenesis in Human Obesity

• Published in: Circulation (New York, N.Y.) N.Y.), 2011-01, Vol.123 (2), p.186-194
• Main Authors: GEALEKMAN, Olga, GUSEVA, Nina, THOMPSON, Michael, PERUGINI, Richard A, CORVERA, Silvia, HARTIGAN, Celia, APOTHEKER, Sarah, GORGOGLIONE, Matthew, GURAV, Kunal, TRAN, Khan-Van, STRAUBHAAR, Juerg, NICOLORO, Sarah, CZECH, Michael P
• Format: Article
• Language: English
• Subjects: Adult; Angiopoietin-Like Protein 4; Angiopoietins - metabolism; Biological and medical sciences; Blood and lymphatic vessels; Body Mass Index; Cardiology. Vascular system; Cardiovascular system; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Gastric Bypass; Humans; Insulin Resistance - physiology; Intra-Abdominal Fat - blood supply; Intra-Abdominal Fat - metabolism; Intra-Abdominal Fat - physiopathology; Medical sciences; Middle Aged; Neovascularization, Pathologic - physiopathology; Neovascularization, Physiologic - physiology; Obesity - metabolism; Obesity - physiopathology; Obesity - surgery; Pharmacology. Drug treatments; Subcutaneous Fat - blood supply; Subcutaneous Fat - metabolism; Subcutaneous Fat - physiopathology; Vasodilator agents. Cerebral vasodilators
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/circulationaha.110.970145

Adipose tissue expands in response to excess caloric intake, but individuals prone to deposit visceral instead of subcutaneous adipose tissue have higher risk of metabolic disease. The role of angiogenesis in the expandability of human adipose tissue depots is unknown. The objective of this study was to measure angiogenesis in visceral and subcutaneous adipose tissue and to establish whether there is a relationship between obesity, metabolic status, and the angiogenic properties of these depots. Angiogenic capacity was determined by quantifying capillary branch formation from human adipose tissue explants embedded in Matrigel, and capillary density was assessed by immunohistochemistry. Subcutaneous adipose tissue had a greater angiogenic capacity than visceral tissue, even after normalization to its higher initial capillary density. Gene array analyses revealed significant differences in expression of angiogenic genes between depots, including an increased subcutaneous expression of angiopoietin-like protein 4, which is proangiogenic in an adipose tissue context. Subcutaneous capillary density and angiogenic capacity decreased with morbid obesity, and subcutaneous, but not visceral, adipose tissue angiogenic capacity correlated negatively with insulin sensitivity. These data imply that subcutaneous adipose tissue has a higher capacity to expand its capillary network than visceral tissue, but this capacity decreases with morbid obesity. The decrease correlates with insulin resistance, suggesting that impairment of subcutaneous adipose tissue angiogenesis may contribute to metabolic disease pathogenesis.