Mette Bjerre

Lack of Dietary Carbohydrates Induces Hepatic Growth Hormone (GH) Resistance in Rats

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Maximilian Bielohuby
  • ,
  • Mandy Sawitzky
  • ,
  • Barbara J M Stoehr
  • ,
  • Peggy Stock
  • ,
  • Dominik Menhofer
  • ,
  • Sabine Ebensing
  • ,
  • Mette Bjerre
  • Jan Frystyk
  • Gerhard Binder
  • ,
  • Christian Strasburger
  • ,
  • Zida Wu
  • ,
  • Bruno Christ
  • ,
  • Andreas Hoeflich
  • ,
  • Martin Bidlingmaier
  • Medicinsk Forskningslaboratorium
  • Institut for Medicinsk Mikrobiologi og Immunologi
  • Medicinsk Endokrinologisk Afd., MEA, NBG
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.
OriginalsprogEngelsk
TidsskriftEndocrinology
Vol/bind152
Nummer5
Sider (fra-til)1948-60
Antal sider13
ISSN0013-7227
DOI
StatusUdgivet - 22 mar. 2011

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