Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment.

Abstract

OBJECTIVE:

To observe the chronic effects of human growth hormone (hGH) and AOD9604 (a C-terminal fragment of hGH) on body weight, energy balance, and substrate oxidation rates in obese (ob/ob) and lean C57BL/6Jmice. In vitro assays were used to confirm whether the effects of AOD9604 are mediated through the hGH receptor, and if this peptide is capable of cell proliferation via the hGH receptor.

METHOD:

Obese and lean mice were treated with hGH, AOD or saline for 14 days using mini-osmotic pumps. Body weight, caloric intake, resting energy expenditure, fat oxidation, glucose oxidation, and plasma glucose, insulin and glycerol were measured before and after treatment. BaF-BO3 cells transfected with the hGH receptor were used to measure in vitro 125I-hGH receptor binding and cell proliferation.

RESULTS:

Both hGH and AOD significantly reduced body weight gain in obese mice. This was associated with increased in vivo fat oxidation and increased plasma glycerol levels (an index of lipolysis). Unlike hGH, however, AOD9604 did not induce hyperglycaemia or reduce insulin secretion. AOD9604 does not compete for the hGH receptor and nor does it induce cell proliferation, unlike hGH.

CONCLUSIONS:

Both hGH and its C-terminal fragment reduce body weight gain, increase fat oxidation, and stimulate lipolysis in obese mice, yet AOD9604 does not interact with the hGH receptor. Thus, the concept of hGH behaving as a pro-hormone is further confirmed. This data shows that fragments of hGH can act in a manner novel to traditional hGH-stimulated pathways.

• Authors: M A Heffernan, A W Thorburn, B Fam, R Summers, B Conway-Campbell, M J Waters, F M Ng
• Journal: International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity (Int J Obes Relat Metab Disord) Vol. 25 Issue 10 Pg. 1442-9 (Oct 2001) England
• PMID: 11673763 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• Peptide Fragments
• delta-hGHR
• Human Growth Hormone

Topics

• Adipose Tissue (metabolism)
• Animals
• Calorimetry, Indirect
• Cells, Cultured
• Energy Metabolism (drug effects)
• Human Growth Hormone (pharmacology)
• Lipolysis (drug effects)
• Male
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Obesity (metabolism)
• Oxidation-Reduction
• Peptide Fragments (pharmacology)
• Weight Loss (drug effects)