title: Growth hormone overexpression in the central nervous system results in hyperphagia-induced obesity associated with insulin resistance and dyslipidemia.
abstract: It is well known that peripherally administered growth hormone (GH) results in decreased body fat mass. However, GH-deficient patients increase their food intake when substituted with GH, suggesting that GH also has an appetite stimulating effect. Transgenic mice with an overexpression of bovine GH in the central nervous system (CNS) were created to investigate the role of GH in CNS. This study shows that overexpression of GH in the CNS differentiates the effect of GH on body fat mass from that on appetite. The transgenic mice were not GH-deficient but were obese and showed increased food intake as well as increased hypothalamic expression of agouti-related protein and neuropeptide Y. GH also had an acute effect on food intake following intracerebroventricular injection of C57BL/6 mice. The transgenic mice were severely hyperinsulinemic and showed a marked hyperplasia of the islets of Langerhans. In addition, the transgenic mice displayed alterations in serum lipid and lipoprotein levels and hepatic gene expression. In conclusion, GH overexpression in the CNS results in hyperphagia-induced obesity indicating a dual effect of GH with a central stimulation of appetite and a peripheral lipolytic effect.
authors.affiliation: Department of Physiology, Göteborg University, Göteborg, Sweden. mohammad.bohlooly@astrazeneca.com
authors.forename: Mohammad
authors.initials: M
authors.lastname: Bohlooly-Y
authors.forename: Mohammad
authors.initials: M
authors.lastname: Bohlooly
authors.forename: Bob
authors.initials: B
authors.lastname: Olsson
authors.forename: Carl E G
authors.initials: CE
authors.lastname: Bruder
authors.forename: Daniel
authors.initials: D
authors.lastname: Lindén
authors.forename: Klara
authors.initials: K
authors.lastname: Sjögren
authors.forename: Mikael
authors.initials: M
authors.lastname: Bjursell
authors.forename: Emil
authors.initials: E
authors.lastname: Egecioglu
authors.forename: Lennart
authors.initials: L
authors.lastname: Svensson
authors.forename: Peter
authors.initials: P
authors.lastname: Brodin
authors.forename: John C
authors.initials: JC
authors.lastname: Waterton
authors.forename: Olle G P
authors.initials: OG
authors.lastname: Isaksson
authors.forename: Frank
authors.initials: F
authors.lastname: Sundler
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.forename: Jan
authors.initials: J
authors.lastname: Oscarsson
authors.forename: Jan
authors.initials: J
authors.lastname: Törnell
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology; D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002153:Calorimetry, Indirect; D002417:Cattle; D015342:DNA Probes; D002149:Energy Intake / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D016678:Genome; D013006:Growth Hormone / Q000008:administration & dosage / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology; D006946:Hyperinsulinism / Q000139:chemically induced; D006949:Hyperlipidemias / Q000235:genetics*; D006963:Hyperphagia / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D007031:Hypothalamus / Q000502:physiology; D007276:Injections, Intraventricular; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000097:blood / Q000209:etiology*
chemical_list: D001786:Blood Glucose; D015342:DNA Probes; D013006:Growth Hormone