Session: SUN-LB-Late-Breaking Poster Session 2
Bench to Bedside
Poster Board SUN-LB-03
A substantial number of obese individuals are relatively insulin sensitive and the etiology for this variation remains unknown. We hypothesized that preserved angiogenesis in expanding fat results in decreased adipose tissue hypoxia and protection from insulin resistance. Adipose tissue oxygenation and circulatory markers of angiogenesis were investigated in obese insulin sensitive (OBIS) as compared to obese insulin resistant (OBIR) and lean subjects.
Non-diabetic, sedentary subjects were enrolled. Obesity was defined as a BMI of 30-42 kg/m2. OBIS subjects were characterized by insulin sensitivity (SI) values above 2.7 x 10-4 min-1/μU/ml. SI was calculated using insulin modified frequently sampled intravenous glucose tolerance test and Minmod model. Total body fat was quantified by dual energy X ray absorptiometry. The partial pressure of oxygen in abdominal adipose tissue (ATpO2) was measured in vivo using a Licox oxygen probe. Plasma angiogenesis factors including angiopoietin like 2 (ANGPTL2), hepatocyte growth factor (HGF), vascular endothelial growth factor A (VEGF-A), epidermal growth factor (EGF), fibroblast growth factor 2 (FGF-2), and endothelin were measured using ELISA.
The obese group (n=12) was 36.4 ± 2.5 y/o with BMI of 34.1 ± 1.3 while the lean group (n=4) was 30.5 ± 2.8 y/o with BMI of 22.9 ± 1.0 (BMI p<0.001; age p=0.23). OBIS (n=6) and OBIR groups were similar in age, BMI and body fat but different in SI. The mean SI was 4.4 ± 0.8, 3.5 ± 0.3, and 1.8 ± 0.2 (x 10-4min-1/μU/ml) in the lean, OBIS, and OBIR groups, respectively (p<0.001, OBIS vs. OBIR). ATpO2 was increased in lean as compared to obese subjects (53 ± 1.9 vs. 39.3 ± 1.5 mm/Hg, p<0.001), and ATpO2 negatively correlated with markers of obesity such as BMI, body fat, and waist circumference (r=-0.8, -0.7, -0.7 respectively, p<0.05). However, ATpO2 was similar between OBIS and OBIR groups (41.1 ± 1.2 vs. 37.7 ± 2.4 mm/Hg, p=0.27) and did not correlate with SI. OBIS subjects had increased levels of ANGPTL2 (335.0 ± 40.7 vs. 159.5 ± 33.5 pg/ml, compared to OBIR, p=.008), and HGF (37.2 ± 3.9 vs. 25.7 ± 1.2 pg/ml, compared to lean, p=0.05). Plasma VEGF-A and FGF-2 levels were similar among groups and EGF and endothelin were not detectable in circulation.
We confirmed that obesity was associated with adipose tissue hypoxia, yet, there was no distinction in ATpO2 between the OBIS and OBIR groups. We found increased plasma levels of ANGPTL2 and HGF in OBIS subjects. ANPLT2 and HGF are secreted by adipose tissue; ANGPLT2 increases with adipocyte differentiation and HGF plays a role in islet mass increase. Our data suggest adipose tissue hypoxia is simply a consequence of fat expansion and is not related to insulin resistance. In contrast, angiogenic factors (ANPLT2 and HGF) might play a role in changes in insulin signaling with obesity.
Nothing to Disclose: HML, NR, CU, CE
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