Abstract 2371: Serum Transthyretin (TTR) In Obese Children And Relationship To Serum Retinol Binding Protein (RBP4) And Inflammation After Lifestyle Changes That Improve Insulin Sensitivity - A Randomized Controlled Intervention
Objectives: Serum RBP4, expressed mainly in liver and fat, is elevated in insulin resistance and obesity and correlates with parameters of the metabolic syndrome. TTR binds and stabilizes RBP4 in serum by reducing its renal excretion. Serum TTR is decreased in many inflammatory illnesses, often in conjunction with protein malnutrition, and RBP4 is secondarily decreased due to enhanced renal excretion. However, we recently reported elevated serum RBP4 levels despite increased markers of inflammation in obese adolescents. We therefore hypothesized that TTR levels are not affected by obesity-related inflammation and may play a permissive role in the regulation of RBP4. We sought to assess the status of serum TTR, its relationship to serum RBP4 its relationship to inflammation and its response to physical activity in adolescent obesity.
Study design: We studied 21 obese and lean adolescents (mean BMI%tile 38±3 kg/m2 for obese (n=15) and 21.3±1.2 kg/m2 for lean (n=6) subjects) at baseline. Obese subjects were insulin resistant relative to lean subjects (4.4±0.3 vs. 0.9±0.4;P<0.0001). Obese subjects were randomized to undergo 3-month lifestyle intervention (healthier diet and increased physical activity, n=8) or education only as a control (n=7).
Results: As reported previously, baseline serum RBP4 levels were higher in obese than in lean subjects and correlated with CRP and IL-6, markers of inflammation. New data show that TTR levels in individual subjects correlated with baseline RBP4 levels (r=0.52; P=0.01) but not with markers of inflammation. Lifestyle intervention in obese subjects resulted in improved insulin sensitivity, decreased inflammatory markers, and a parallel decrease in serum RBP4 levels; in contrast, TTR levels increased (from 0.17±0.01 to 0.19±0.01; P=0.02) but did not correlate with the reduction in inflammatory markers. Serum levels of TTR and RBP4 did not change in the obese control subjects.
Conclusions: Serum TTR levels are associated with RBP4 but not with markers of inflammation in adolescents. Lifestyle intervention reduces serum RBP4 levels independently of TTR in obese subjects, and this mechanism most likely reflects decreased production of RBP4 in liver and/or fat rather than accelerated renal clearance of RBP4.