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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Keyword

Adipose Tissue

anatomy & histology

Animals

Base Sequence

Blood Glucose

metabolism

Body Weight

Calorimetry

Indirect

Cattle

DNA Probes

Energy Intake

drug effects

Female

Gene Expression Regulation

genetics

physiology

Genome

Growth Hormone

administration & dosage

genetics

pharmacology

physiology

Hyperinsulinism

chemically induced

Hyperlipidemias

genetics

Hyperphagia

blood

genetics

physiopathology

Hypothalamus

physiology

Injections

Intraventricular

Insulin Resistance

genetics

Male

Mice

Mice

Inbred C57BL

Mice

Transgenic

Obesity

blood

etiology

Publication and Content Type

ref (subject category)

art (subject category)