Human Growth Hormone Fragment 176-191 (AOD-9604) is a synthetic peptide fragment corresponding to the 176-191 region of the C-terminus of human growth hormone (hGH). This specific region was identified through research aimed at isolating the lipolytic (fat-burning) properties of hGH while eliminating its growth-promoting and insulin-antagonistic effects. The discovery stemmed from the observation that the full hGH molecule could promote fat loss, but its clinical use was limited by side effects related to its mitogenic and diabetogenic actions. AOD-9604 represents a significant research tool as it appears to dissociate the metabolic effects of hGH from its growth-promoting effects, making it a compound of interest primarily for studying lipid metabolism and obesity-related pathways.
Quick Facts
| Also Known As | HGH Fragment 176-191, AOD-9604, Anti-Obesity Drug-9604, Growth Hormone Lipolytic Fragment |
|---|---|
| Sequence | Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe |
| Molecular Formula | C78H122N22O23S2 |
| Molecular Weight | 1813.1 Da |
Research Parameters
| Half-Life | Unknown (Estimated to be short, likely minutes to a few hours based on peptide nature, but not definitively established in literature) |
|---|---|
| Stability | Lyophilized powder is stable for at least 24 months when stored at -20°C, protected from light and moisture. After reconstitution with appropriate solvent, the solution should be stored at 2-8°C and used within a short period (e.g., 7-14 days) to ensure stability and prevent bacterial growth, although specific validated stability data for the reconstituted solution is limited in public literature. |
| Solubility | Bacteriostatic Water (0.9% Benzyl Alcohol) or Sterile Water for Injection. A slight acidic pH (e.g., using acetic acid) may be required for complete solubilization due to its sequence. |
| Vial Size | 2 mg |
| Storage (Lyophilized) | -20°C, protect from light and moisture |
| Storage (Reconstituted) | 2-8°C (refrigerated), protected from light. Use within a short timeframe (e.g., 7-14 days). |
| Typical Research Dose | 300-1000 mcg per day |
| Cycle Parameters | In research contexts, daily subcutaneous injection for periods of 4 to 12 weeks. Specific 'on/off' cycling protocols are not well-defined in published literature, with most studies employing continuous daily dosing for the trial duration. |
| Amino Acid Count | 16 |
Mechanism of Action
AOD-9604's primary mechanism is believed to be the direct stimulation of lipolysis (fat breakdown) and inhibition of lipogenesis (fat storage) in adipose tissue, without engaging the growth hormone receptor in a manner that promotes systemic IGF-1 release or growth. Its actions are mediated through a receptor pathway distinct from that of full-length hGH.
Direct Lipolytic Stimulation: The peptide binds to a specific site on adipocytes (fat cells), potentially a truncated form of the growth hormone receptor or a separate receptor, activating hormone-sensitive lipase (HSL). This enzyme catalyzes the hydrolysis of stored triglycerides into free fatty acids and glycerol.
Inhibition of Lipogenesis: AOD-9604 is thought to antagonize the antilipolytic action of insulin in adipose tissue. It may interfere with insulin signaling pathways that promote fat storage, thereby reducing the conversion of glucose into fatty acids.
Beta-3 Adrenergic Receptor Interaction: Some evidence suggests the peptide may enhance the activity of beta-3 adrenergic receptors, which are key mediators of thermogenesis and lipolysis in brown and white adipose tissue.
Metabolic Rate Modulation: Research indicates it may increase metabolic rate and promote the utilization of fat as an energy source, contributing to a reduction in fat mass without significant effects on lean mass or blood glucose levels.
Research Applications
Obesity and Metabolic Syndrome Research: AOD-9604 has been extensively studied in models of obesity. Research indicates it can reduce body weight and specifically decrease fat mass without causing loss of lean muscle mass. It appears to improve metabolic parameters such as cholesterol profiles and may enhance insulin sensitivity in obese states, making it a tool for investigating pathways of weight regulation and metabolic health.
Lipid Metabolism Studies: The peptide serves as a precise tool to study the direct lipolytic and anti-lipogenic pathways in adipose tissue, independent of the broader endocrine effects of full-length growth hormone. This allows researchers to isolate and understand the specific molecular mechanisms controlling fat breakdown and storage.
Injury and Cartilage Research: Some preclinical studies have explored its potential role in cartilage protection and repair. It may stimulate chondrocyte proliferation and the synthesis of extracellular matrix components like proteoglycans, suggesting utility in models of osteoarthritis or joint injury.
Wound Healing: Preliminary animal research has indicated that AOD-9604 might accelerate the rate of wound closure, potentially by modulating local growth factors and promoting tissue remodeling, providing a model for studying non-diabetic wound healing processes.
Safety & Side Effects
Based on available clinical trial data, AOD-9604 appears to have a favorable safety profile with minimal reported side effects. In human studies, reported adverse events were generally mild and comparable to placebo, with no significant changes in vital signs, hematology, or clinical chemistry parameters. No serious adverse events related to the peptide were reported. Importantly, studies have not shown the peptide to induce the side effects associated with full-length hGH, such as acromegaly-like symptoms, insulin resistance, or carpal tunnel syndrome. Theoretical concerns remain minimal due to its lack of interaction with the growth-promoting domain of the GH receptor. Anecdotal reports from non-clinical use are scarce and not scientifically verified.
Dosage Information
All information regarding administration and dosing is derived from preclinical and clinical research studies and is for research purposes only. In human clinical trials, AOD-9604 has been administered via subcutaneous injection. Typical research doses in human studies have ranged from 300 mcg to 1 mg per day. The frequency is typically once-daily administration. Study durations in clinical trials have varied from 4 to 12 weeks. Animal studies have used a wide range of doses, often calculated on a per-body-weight basis (e.g., mcg/kg).
References
Heffernan, M., et al. '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.' Endocrinology, 2001.
Ng, F.M., et al. 'Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone.' Hormone Research, 2000.
Ehrnborg, C., et al. 'The growth hormone/insulin-like growth factor-I axis hormones and bone markers in elite athletes in response to a maximum exercise test.' Growth Hormone & IGF Research, 2003.
Kirsten, R., et al. 'AOD9604: a new orally active weight loss drug.' International Journal of Obesity, 2002.
He, M. L., et al. 'AOD9604, a synthetic peptide variant of hGH, stimulates chondrocyte proliferation and extracellular matrix production.' Osteoarthritis and Cartilage, 2006.
Ng, F.M., et al. 'Preliminary studies of a synthetic fragment of human growth hormone with potent lipolytic activity.' Proceedings of the Endocrine Society of Australia, 1995.