Growth differentiation factor 15 increases following oral glucose ingestion: Effect of meal composition and obesity

Abstract

Objective: Growth differentiation factor 15 (GDF15) is a cardiovascular biomarker belonging to the transforming growth factor-? superfamily. Increased GDF15 concentrations are associated with insulin resistance, diabetes and obesity. We investigated the physiological effects of meal composition and obesity on the regulation of systemic GDF15 levels. Design: Lean (n = 8) and obese (n = 8) individuals received a carbohydrate-or fat-rich meal, a 75 g oral glucose load (OGTT) or short-Term fasting. OGTTs were performed in severely obese patients (n = 6) pre-and post-bariatric surgery. Methods: Circulating serum GDF15 concentrations were studied in lean and obese individuals in response to different meals, OGTT or short-Term fasting, and in severely obese patients pre-and post-bariatric surgery. Regulation of GDF15 mRNA levels and protein release were evaluated in the human hepatic cell line HepG2. Results: GDF15 concentrations steadily decrease during short-Term fasting in lean and obese individuals. Carbohydrate-and fat-rich meals do not influence GDF15, whereas an OGTT leads to a late increase in GDF15 levels. The positive effect of OGTT on GDF15 levels is also preserved in severely obese patients, pre-and post-bariatric surgery. We further studied the regulation of GDF15 mRNA levels and protein release in HepG2, finding that glucose and insulin independently stimulate both GDF15 transcription and secretion. Conclusion: In summary, high glucose and insulin peaks upregulate GDF15 transcription and release. The nutrient-induced increase in GDF15 levels depends on rapid glucose and insulin excursions following fast-digesting carbohydrates, but not on the amount of calories taken in.