title: Lack of dietary carbohydrates induces hepatic growth hormone (GH) resistance in rats.
abstract: GH is a well established regulator of growth, lipid, and glucose metabolism and therefore important for fuel utilization. However, little is known about the effects of macronutrients on the GH/IGF system. We used low-carbohydrate/high-fat diets (LC-HFD) as a model to study the impact of fat, protein, and carbohydrates on the GH/IGF-axis; 12-wk-old Wistar rats were fed either regular chow, a moderate, protein-matched LC-HFD, or a ketogenic LC-HFD (percentage of fat/protein/carbohydrates: chow, 16.7/19/64.3; LC-HF-1, 78.7/19.1/2.2; LC-HF-2, 92.8/5.5/1.7). After 4 wk, body and tibia length, lean body mass, and fat pad weights were measured. Furthermore, we investigated the effects of LC-HFD on 1) secretion of GH and GH-dependent factors, 2) expression and signaling of components of the GH/IGF system in liver and muscle, and 3) hypothalamic and pituitary regulation of GH release. Serum concentrations of IGF-I, IGF binding protein-1, and IGF binding protein-3 were lower with LC-HF-1 and LC-HF-2 (P < 0.01). Both LC-HFD-reduced hepatic GH receptor mRNA and protein expression, decreased basal levels of total and phosphorylated Janus kinase/signal transducers and activators of transcription signaling proteins and reduced hepatic IGF-I gene expression. Hypothalamic somatostatin expression was reduced only with LC-HF-1, leading to increased pituitary GH secretion, higher IGF-I gene expression, and activation of IGF-dependent signaling pathways in skeletal muscle. In contrast, despite severely reduced IGF-I concentrations, GH secretion did not increase with LC-HF-2 diet. In conclusion, lack of carbohydrates in LC-HFD induces hepatic GH resistance. Furthermore, central feedback mechanisms of the GH/IGF system are impaired with extreme, ketogenic LC-HFD.
authors.affiliation: Endocrine Research Unit, Medizinische Klinik-Innenstadt, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Bielohuby
authors.forename: Mandy
authors.initials: M
authors.lastname: Sawitzky
authors.forename: Barbara J M
authors.initials: BJ
authors.lastname: Stoehr
authors.forename: Peggy
authors.initials: P
authors.lastname: Stock
authors.forename: Dominik
authors.initials: D
authors.lastname: Menhofer
authors.forename: Sabine
authors.initials: S
authors.lastname: Ebensing
authors.forename: Mette
authors.initials: M
authors.lastname: Bjerre
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Gerhard
authors.initials: G
authors.lastname: Binder
authors.forename: Christian
authors.initials: C
authors.lastname: Strasburger
authors.forename: Zida
authors.initials: Z
authors.lastname: Wu
authors.forename: Bruno
authors.initials: B
authors.lastname: Christ
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoeflich
authors.forename: Martin
authors.initials: M
authors.lastname: Bidlingmaier
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D050528:Diet, Carbohydrate-Restricted; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000494:pharmacology*; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology; D004044:Dietary Proteins / Q000008:administration & dosage / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D013006:Growth Hormone / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism
chemical_list: D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004044:Dietary Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D011986:Receptors, Somatotropin; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3