title: Low-protein diet induces, whereas high-protein diet reduces hepatic FGF21 production in mice, but glucose and not amino acids up-regulate FGF21 in cultured hepatocytes.
abstract: Fibroblast growth factor 21 (FGF21) is a polypeptide secreted by the liver and involved in several metabolic processes such as thermogenesis and lipid oxidation. The nutritional mechanisms controlling FGF21 production are poorly understood. This study aimed to investigate how dietary carbohydrates and proteins impact FGF21 production and how in turn, FGF21 is involved in the metabolic adaptation to changes in the carbohydrate and protein contents of the diet. For that purpose, we fed 25 male C57BL/6 mice diets composed of different protein and carbohydrate contents (normal-protein and carbohydrate diet (N=9, NPNC), low-protein high-carbohydrate diet (N=8, LPHC), high-protein low-carbohydrate diet (N=8, HPLC) for 3 weeks. We measured liver Fgf21 gene expression, synthesis and secretion as well as different parameters related to energy and glucose metabolism. We also investigated the direct role of amino acids and glucose in the control of Fgf21 gene expression in hepatocyte primary cultures (n=6). In vivo, FGF21 responds acutely to LPHC intake whereas under an HPLC diet, plasma FGF21 circulating levels are low in the fasted and refed states. In hepatocytes, Fgf21 expression was controlled by glucose but not amino acids. Both diets increased the thermic effect of feeding (TEF) and ketogenesis was increased in fasted HPLC mice. The results presented suggest that dietary glucose, rather than amino acids, directly controls FGF21 secretion, and that FGF21 may be involved in the increased TEF response to LPHC. The effects of the HPLC diet on ketogenesis and TEF are probably controlled by other metabolic pathways.
authors: UMR PNCA, AgroParisTech, INRA, Université Paris Saclay, 16 rue Claude Bernard, F-75005 Paris, France.
authors: Tristan
authors: T
authors: Chalvon-Demersay
authors: UMR PNCA, AgroParisTech, INRA, Université Paris Saclay, 16 rue Claude Bernard, F-75005 Paris, France.
authors: Patrick C
authors: PC
authors: Even
authors: UMR PNCA, AgroParisTech, INRA, Université Paris Saclay, 16 rue Claude Bernard, F-75005 Paris, France.
authors: Daniel
authors: D
authors: Tomé
authors: UMR PNCA, AgroParisTech, INRA, Université Paris Saclay, 16 rue Claude Bernard, F-75005 Paris, France.
authors: Catherine
authors: C
authors: Chaumontet
authors: UMR PNCA, AgroParisTech, INRA, Université Paris Saclay, 16 rue Claude Bernard, F-75005 Paris, France.
authors: Julien
authors: J
authors: Piedcoq
authors: UMR PNCA, AgroParisTech, INRA, Université Paris Saclay, 16 rue Claude Bernard, F-75005 Paris, France.
authors: Claire
authors: C
authors: Gaudichon
authors: UMR PNCA, AgroParisTech, INRA, Université Paris Saclay, 16 rue Claude Bernard, F-75005 Paris, France. Electronic address: dalila.azzout_marniche@agroparistech.fr.
authors: Dalila
authors: D
authors: Azzout-Marniche
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D050528:Diet, Carbohydrate-Restricted / Q000009:adverse effects; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D004044:Dietary Proteins / Q000008:administration & dosage*; D004734:Energy Metabolism; D005346:Fibroblast Growth Factors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D019518:Postprandial Period; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014886:Weaning
chemical_list: D000596:Amino Acids; D004044:Dietary Proteins; D012333:RNA, Messenger; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D005947:Glucose
keywords: Amino acids; Calorimetry; FGF21; Glucose; Physiology