Growth hormone overexpression in the central nervous system results in hyperphagia-induced obesity associated with insulin resistance and dyslipidemia.
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.
Bohlooly-Y
Mohammad
M
Department of Physiology, Göteborg University, Göteborg, Sweden. mohammad.bohlooly@astrazeneca.com
Bohlooly
Mohammad
M
Olsson
Bob
B
Bruder
Carl E G
CE
Lindén
Daniel
D
Sjögren
Klara
K
Bjursell
Mikael
M
Egecioglu
Emil
E
Svensson
Lennart
L
Brodin
Peter
P
Waterton
John C
JC
Isaksson
Olle G P
OG
Sundler
Frank
F
Ahrén
Bo
B
Ohlsson
Claes
C
Oscarsson
Jan
J
Törnell
Jan
J
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*
D001786:Blood Glucose; D015342:DNA Probes; D013006:Growth Hormone