ECE2016 Eposter Presentations Obesity (69 abstracts)
Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Introduction: Growth differentiation factor 15 (GDF15) has recently been characterized as a cardiovascular risk factor. GDF15 correlates with insulin resistance and obesity in cross-sectional studies and exerts anorexigenic effects in interventional rodent studies. GDF15 has been proposed as a possible therapeutic target in the treatment of obesity, however its meal- and nutrient-dependent regulation in humans has not been investigated previously.
Methods: Profiles of GDF15 plasma concentrations were studied in lean and obese individuals in response to carbohydrate-rich and fat-rich meals, a 75 g oral glucose load (OGTT) or fasting. Human hepatic HepG2 cells were stimulated with glucose- and insulin, and the effects on GDF15 mRNA levels and protein release in the supernatant were evaluated.
Results: In lean and obese individuals, fasting was associated with a steady decrease in plasma GDF15 concentrations. OGTT inhibited this decrease with GDF15 rising back to baseline levels 23 hours after glucose ingestion, while carbohydrate- and fat-rich meals did not have a significant effect. In HepG2 cells, glucose and insulin independently stimulate GDF15 transcription as well as secretion.
Conclusion: GDF-15 decreases during fasting and increases in response to high peaks in glucose and insulin concentrations following oral glucose ingestion in men. These changes are, at least in part, mediated via direct effects of glucose and insulin on GDF15 transcription and release. These data provide the first evidence on nutrient-related changes in GDF-15 concentrations in humans.