Growth hormone overexpression in the central nervous system results in hyperphagia-induced obesity associated with insulin resistance and dyslipidemia

Mohammad Bohlooly, Bob Olsson, Carl E G Bruder, Daniel Lindén, Klara Sjögren, Mikael Bjursell, Emil Egecioglu, Lennart Svensson, Peter Brodin, John C. Waterton, Olle G P Isaksson, Frank Sundler, Bo Ahrén, Claes Ohlsson, Jan Oscarsson, Jan Törnell

    Research output: Contribution to journalArticlepeer-review

    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.
    Original languageEnglish
    Pages (from-to)51-62
    Number of pages11
    JournalDiabetes
    Volume54
    Issue number1
    DOIs
    Publication statusPublished - Jan 2005

    Keywords

    • anatomy & histology: Adipose Tissue
    • Animals
    • Base Sequence
    • metabolism: Blood Glucose
    • Body Weight
    • Calorimetry, Indirect
    • Cattle
    • DNA Probes
    • drug effects: Energy Intake
    • Female
    • genetics: Gene Expression Regulation
    • Genome
    • administration & dosage: Growth Hormone
    • chemically induced: Hyperinsulinism
    • genetics: Hyperlipidemias
    • blood: Hyperphagia
    • physiology: Hypothalamus
    • Injections, Intraventricular
    • genetics: Insulin Resistance
    • Male
    • Mice
    • Mice, Inbred C57BL
    • Mice, Transgenic
    • blood: Obesity

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