Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism
American Journal of Physiology-Endocrinology and MetabolismPublished 1 September 2000Open access
Mark Heffernan, Wei Jiang, A W Thorburn, Frank M Ng
Citations33
SJR quartileQ1
SJR score1.39
SNIP1.02
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TL;DR
It is indicated that oral administration of AOD-9401 alters lipid metabolism in adipose tissue, resulting in a reduction of weight gain in obese animals, and this small synthetic hGH peptide has potential in the treatment of human obesity.
Abstract
A small synthetic peptide sequence of human growth hormone (hGH), AOD-9401, has lipolytic and antilipogenic activity similar to that of the intact hormone. Here we report its effect on lipid metabolism in rodent models of obesity and in human adipose tissue to assess its potential as a pharmacological agent for the treatment of human obesity. C57BL/6J (ob/ob) mice were orally treated with either saline (n = 8) or AOD-9401 (n = 10) for 30 days. From day 16 onward, body weight gain in AOD-9401-treated animals was significantly lower than that of saline-treated controls. Food consumption did not differ between the two groups. Analyses of adipose tissue ex vivo revealed that AOD-9401 significantly reduced lipogenic activity and increased lipolytic activity in this tissue. Increased catabolism was also reflected in an acute increase in energy expenditure and glucose and fat oxidation in ob/ob mice treated with AOD-9401. In addition, AOD-9401 increased in vitro lipolytic activity and decreased lipogenic activity in isolated adipose tissue from obese rodents and humans. Together, these findings indicate that oral administration of AOD-9401 alters lipid metabolism in adipose tissue, resulting in a reduction of weight gain in obese animals. The marked lipolytic and antilipogenic actions of AOD-9401 in human adipose tissues suggest that this small synthetic hGH peptide has potential in the treatment of human obesity.
Keywords
Medicine
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Journal of Pediatric Endocrinology and MetabolismAdverse Events During Growth Hormone Therapy
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Biochemical JournalGrowth hormone decreases the response to anti-lipolytic agonists and decreases the levels of Gi2 in rat adipocytes
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International journal of peptide & protein researchProbing the structure of human growth hormone by limited proteolysis
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DiabetesInsulin Potentiating Action of Synthetic Peptides Relating to the Amino Terminal Sequence of Human Growth Hormone
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EndocrinologyProteolytic Cleavage of Human Growth Hormone (hGH) by Rat Tissues<i>in Vitro</i>: Influence on the Kinetics of Exogenously Administered hGH*
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There is experimental evidence that several of these effects are produced by different parts of the molecule, and how these active centers produce the corresponding physiological effects is still an unsolved problem.
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Journal of Biological ChemistryMitogenic and receptor activities of human growth hormone 108-129.
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PubMedReduction of cumulative body weight gain and adipose tissue mass in obese mice: response to chronic treatment with synthetic hGH 177-191 peptide.
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PubMedSimple, inexpensive computerized rodent activity meters.
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Molecular and Cellular EndocrinologyActivity of growth hormone peptides bGH 96–133 and hGH 95–133 in 3T3-F442A cells
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PubMedStimulation of 3-O-methylglucose transport in adipocytes by a synthetic human growth hormone fragment.
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