Growth differentiation factor 15 increases following oral glucose ingestion: effect of meal composition and obesity
MH Schernthaner-Reiter, D Kasses…�- European journal of�…, 2016 - academic.oup.com
MH Schernthaner-Reiter, D Kasses, C Tugendsam, M Riedl, S Peric, G Prager, M Krebs…
European journal of endocrinology, 2016•academic.oup.comObjective Growth differentiation factor 15 (GDF15) is a cardiovascular biomarker belonging
to the transforming growth factor-β 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�…
to the transforming growth factor-β 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�…
Objective
Growth differentiation factor 15 (GDF15) is a cardiovascular biomarker belonging to the transforming growth factor-β 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.
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