title: 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-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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Division of Endocrinology and MetabolismDepartment of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Marie Helene
authors.initials: MH
authors.lastname: Schernthaner-Reiter
authors.affiliation: Clinical Division of Endocrinology and MetabolismDepartment of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Dominik
authors.initials: D
authors.lastname: Kasses
authors.affiliation: Clinical Division of Endocrinology and MetabolismDepartment of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Christina
authors.initials: C
authors.lastname: Tugendsam
authors.affiliation: Clinical Division of Endocrinology and MetabolismDepartment of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Riedl
authors.affiliation: Clinical Division of Endocrinology and MetabolismDepartment of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Slobodan
authors.initials: S
authors.lastname: Peric
authors.affiliation: Division of General SurgeryDepartment of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Prager
authors.affiliation: Clinical Division of Endocrinology and MetabolismDepartment of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Krebs
authors.affiliation: Clinical Division of Endocrinology and MetabolismDepartment of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Miriam
authors.initials: M
authors.lastname: Promintzer-Schifferl
authors.affiliation: Clinical Division of Endocrinology and MetabolismDepartment of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Clodi
authors.affiliation: Clinical Division of Endocrinology and MetabolismDepartment of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Anton
authors.initials: A
authors.lastname: Luger
authors.affiliation: Clinical Division of Endocrinology and MetabolismDepartment of Internal Medicine III, Medical University of Vienna, Vienna, Austria greisa.vila@meduniwien.ac.at.
authors.forename: Greisa
authors.initials: G
authors.lastname: Vila
mesh_terms: D000284:Administration, Oral; D000328:Adult; D050110:Bariatric Surgery / Q000639:trends; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D004041:Dietary Fats / Q000008:administration & dosage*; D002149:Energy Intake / Q000502:physiology; D005260:Female; D005947:Glucose / Q000008:administration & dosage*; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D062407:Meals / Q000502:physiology*; D009765:Obesity / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D016037:Single-Blind Method
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D007328:Insulin; D005947:Glucose