somatotropin-(177-191) and Obesity

A lipolytic domain (AOD9401) of human growth hormone (hGH) which resides in the carboxyl terminus of the molecule and contains the amino acid residues 177-191, has been synthesized using solid-phase peptide synthesis techniques. AOD9401 stimulated hormone-sensitive lipase and inhibited acetyl coenzyme A carboxylase (acetyl CoA carboxylase) in isolated rat adipose tissues, in a similar manner to the actions of the intact hGH molecule. The synthetic lipolytic domain mimicked the effect of the intact growth hormone on diacylglycerol release in adipocytes. Chronic treatment of obese Zucker rats with AOD9401 for 20 days reduced the body weight gain of the animals, and the average cell size of the adipocytes of the treated animals decreased from 110 to 80 microm in diameter. Unlike hGH, synthetic AOD9401 did not induce insulin resistance or glucose intolerance in the laboratory animals after chronic treatment. The results suggest that AOD9401 has the potential to be developed into a therapeutic agent for the control of obesity.

Topics: Adipocytes; Adipose Tissue; Animals; Blood Glucose; Body Weight; Cell Separation; Cell Size; Female; Growth Hormone; Humans; Insulin Resistance; Lipid Metabolism; Male; Obesity; Peptide Fragments; Rats; Rats, Zucker; Time Factors

The effects of long-term treatment of C57BL/6J (ob/ob) mice with a synthetic carboxylterminal sequence of human growth hormone, hGH 177-191, were investigated. Results indicate that the hGH 177-191 reduced the cumulative body weight gain, and decreased the adipose tissue mass. The lipogenesis in adipose tissues was significantly inhibited by the treatment with hGH 177-191. These findings support the suggestion that hGH 177-191 is the functional domain of hGH for the antilipogenic actions of the intact hormone both in vivo and in vitro. The hGH 177-191 peptide has the potential to be an effective compound for the treatment of human obesity and for the improvement of meat qualities in farm animals.

Topics: Adipose Tissue; Amino Acid Sequence; Animals; Cholesterol; Eating; Female; Growth Hormone; Lipids; Male; Mice; Mice, Obese; Molecular Sequence Data; Obesity; Peptide Fragments; Sex Factors; Triglycerides; Weight Gain

The effect of a synthetic C-terminal peptide sequence of human growth hormone, Leu-Arg-Ile-Val-Gln-Cys-Arg-Val-Ser-Glu-Gly-Ser-Cys-Gly-Phe (hGH 177-191) on glucose transport in adipocytes isolated from genetically-obese Zucker rats was investigated. The results showed that the synthetic peptide induced a reduction of basal and insulin-stimulated D[1-14C]-2-deoxyglucose uptake in isolated adipocytes. In comparison with the intact molecule of human growth hormone (hGH), the synthetic peptide at equimolar concentrations was found to be more potent. These findings are consistent with the suggestion that the functional domain responsible for the antilipogenic activity of hGH resides in the C-terminal region of the hGH molecule and the effect on glucose transport may contribute, at least in part, to the antilipogenic property of the peptide hGH 177-191 as well as of the intact hormone.

Topics: Adipose Tissue; Amino Acid Sequence; Animals; Epididymis; Glucose; Growth Hormone; Humans; Insulin; Lipids; Male; Molecular Sequence Data; Obesity; Peptide Fragments; Rats; Rats, Zucker