Overview
AOD9604 is a synthetic 16-residue peptide corresponding to the C-terminal region of human growth hormone (residues 177 to 191) with an added N-terminal tyrosine, and is also described as Tyr-hGH(177-191). Earlier work had shown that the synthetic hGH 177-191 fragment had antilipogenic activity in rat adipose tissue identical to that of the intact hormone, and that a related synthetic fragment had lipolytic and antilipogenic activity in rodent models1,2.
Published research is preclinical and centres on lipid metabolism in rodent models of obesity, including obese Zucker rats, ob/ob mice and beta(3)-adrenergic receptor knockout mice3,4,5. A separate study examined the peptide in a rabbit model of collagenase-induced knee osteoarthritis6.
Mechanism of action
As described in the research literature
As described in the research literature, the C-terminal domain of growth hormone was proposed to carry the hormone's antilipogenic activity: the hGH 177-191 fragment reduced lipogenesis in rat epididymal fat pads without a significant lipolytic effect in that assay1. A related fragment, AOD-9401, was reported to reduce lipogenic and increase lipolytic activity in isolated adipose tissue from obese rodents and in human adipose tissue in vitro2.
For AOD9604 itself, in vitro work in cells transfected with the hGH receptor reported that the peptide did not compete for receptor binding and did not induce cell proliferation, unlike intact hGH4. In obese mice, both hGH and AOD9604 increased expression of beta(3)-adrenergic receptor RNA in adipose tissue; however, the effect on energy expenditure and fat oxidation was still observed acutely in beta(3)-AR knockout mice, and the authors concluded that the lipolytic actions are not mediated directly through this receptor5.
Research areas
What published studies have examined
Lipid metabolism in rodent obesity models
Studies in obese Zucker rats examined body weight gain, adipose tissue lipolytic activity and insulin sensitivity by euglycaemic clamp3. Work in ob/ob and lean C57BL/6J mice measured body weight, caloric intake, resting energy expenditure, fat and glucose oxidation, and plasma glucose, insulin and glycerol, comparing AOD9604 with intact hGH4.
Sources [3] [4]
Growth hormone receptor and adrenergic signalling
Receptor binding and proliferation assays in hGH receptor-transfected BaF-BO3 cells were used to test whether AOD9604 acts through the growth hormone receptor4. Studies in obese and beta(3)-AR knockout mice examined beta(3)-adrenergic receptor expression and its contribution to the lipolytic response5.
Sources [4] [5]
Origin of the C-terminal fragment
Earlier work characterised the antilipogenic activity of the synthetic hGH 177-191 sequence in rat fat pads1, and the lipolytic and antilipogenic activity of the related fragment AOD-9401 in ob/ob mice and in isolated rodent and human adipose tissue2.
Sources [1] [2]
Cartilage model
A study in New Zealand white rabbits with collagenase-induced knee osteoarthritis compared AOD9604, hyaluronic acid, their combination and saline, assessing cartilage by gross morphological and histopathological scoring and recording the duration of lameness6.
Sources [6]
Specifications
- Sequence
- Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe (YLRIVQCRSVEGSCGF), with a disulfide bridge between the two cysteines
- Molecular formula
- C78H123N23O23S2
- Molecular weight
- 1815.1 g/mol
- CAS number
- 221231-10-3
- Form
- White to off-white lyophilised powder in a sealed vial (5 mg or 10 mg)
- Storage
- Store lyophilised powder at -20 °C, protected from light and moisture. Once reconstituted, keep refrigerated at 2 to 8 °C and protect from light.
- Solubility and reconstitution
- Reconstitute with bacteriostatic water. Add the diluent slowly down the inside wall of the vial and swirl gently until clear; do not shake.
References
- 1
Antilipogenic action of synthetic C-terminal sequence 177-191 of human growth hormone.
Wu Z, Ng FM Biochemistry and Molecular Biology International, 1993.
PubMed 8358331 ↗
- 2
- 3
- 4
Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment.
Heffernan MA, Thorburn AW, Fam B, et al. International Journal of Obesity and Related Metabolic Disorders, 2001.
PubMed 11673763 ↗DOI 10.1038/sj.ijo.0801740 ↗
- 5
The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice.
Heffernan M, Summers RJ, Thorburn A, et al. Endocrinology, 2001.
PubMed 11713213 ↗DOI 10.1210/endo.142.12.8522 ↗
- 6
Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model.
Kwon DR, Park GY Annals of Clinical and Laboratory Science, 2015.
PubMed 26275694 ↗