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 acarbohydrate- 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.
RCT Entities:
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 obesepatients (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 obesepatients 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 obesepatients, 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.
Authors: Marta Díaz; Gemma Carreras-Badosa; Joan Villarroya; Aleix Gavaldà-Navarro; Judit Bassols; Francis de Zegher; Abel López-Bermejo; Francesc Villarroya; Lourdes Ibáñez Journal: Pediatr Res Date: 2022-07-11 Impact factor: 3.953
Authors: Satish Patel; Anna Alvarez-Guaita; Audrey Melvin; Debra Rimmington; Alessia Dattilo; Emily L Miedzybrodzka; Irene Cimino; Anne-Catherine Maurin; Geoffrey P Roberts; Claire L Meek; Samuel Virtue; Lauren M Sparks; Stephanie A Parsons; Leanne M Redman; George A Bray; Alice P Liou; Rachel M Woods; Sion A Parry; Per B Jeppesen; Anders J Kolnes; Heather P Harding; David Ron; Antonio Vidal-Puig; Frank Reimann; Fiona M Gribble; Carl J Hulston; I Sadaf Farooqi; Pierre Fafournoux; Steven R Smith; Jorgen Jensen; Danna Breen; Zhidan Wu; Bei B Zhang; Anthony P Coll; David B Savage; Stephen O'Rahilly Journal: Cell Metab Date: 2019-01-10 Impact factor: 27.287
Authors: Axel C Carlsson; Christoph Nowak; Lars Lind; Carl Johan Östgren; Fredrik H Nyström; Johan Sundström; Juan Jesus Carrero; Ulf Riserus; Erik Ingelsson; Tove Fall; Johan Ärnlöv Journal: Ups J Med Sci Date: 2019-12-05 Impact factor: 2.384
Authors: Francis de Zegher; Marta Díaz; Joan Villarroya; Montserrat Cairó; Abel López-Bermejo; Francesc Villarroya; Lourdes Ibáñez Journal: Sci Rep Date: 2021-03-29 Impact factor: 4.379