What Is AOD-9604?

AOD-9604 is a synthetic peptide fragment derived from the C-terminal end of human growth hormone (hGH). Specifically, it corresponds to amino acids 177–191 of hGH with an added tyrosine for stability. Researchers first developed it to explore how smaller peptide fragments of hGH might influence fat metabolism pathways without engaging the broader hormone system.

(Reference: Ng et al., 2000)

How Has AOD-9604 Been Studied in Research?

AOD-9604 has been examined in multiple experimental systems:

• In vitro assays to assess receptor interactions, gene expression, and toxicity.

• Animal models to study metabolic pathways such as lipid breakdown and receptor regulation.

• Human studies to monitor biomarkers like IGF-1, glucose tolerance, and overall safety.

These investigations provide insight into how the fragment behaves biologically, even though results vary depending on the model used.

(Reference: Heffernan et al., 2001)

Observations Reported in Studies

Laboratory and published research on AOD-9604 has reported:

• Receptor Pathways – Upregulation of beta-3 adrenergic receptors in adipose tissue has been observed in animal models, suggesting involvement in fat-cell signaling.

• IGF-1 Independence – Both animal and human studies consistently show no change in IGF-1 levels, distinguishing AOD-9604 from intact growth hormone.

• Safety Markers – Toxicology programs and clinical studies found no genotoxic activity, no antibody formation, and a tolerability profile comparable to placebo groups.

(Reference: Stier et al., 2013)

Advantages and Limitations in Experimental Settings

Advantages

1. Selective Pathway Focus – Allows researchers to study fat metabolism mechanisms without triggering growth-hormone-related pathways.

2. Safety Data – Extensive testing in vitro, in animals, and in human trials has documented a consistent safety profile.

3. Multiple Models – The peptide has been evaluated across diverse systems, making it a flexible tool for laboratory research.

Limitations

• Mechanism Uncertainty – While certain receptor pathways are implicated, the exact molecular targets remain under investigation.

• Translational Gaps – Findings from rodent and cell studies do not always align with results seen in human trials.

• Narrow Scope – AOD-9604’s activity appears limited to metabolic pathways, which may restrict broader research applications.

(Reference: Moré & Kenley, 2014)

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• Ng, F.M., et al. (2000). Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Hormone Research, 53(6), 274–278.

• Heffernan, M., et al. (2001). The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism in obese and beta-3 AR knockout mice. Endocrinology, 142(12), 5182–5189.

• Stier, H., Vos, E., & Kenley, D. (2013). Safety and tolerability of the hexadecapeptide AOD9604 in humans. Journal of Endocrinology and Metabolism, 3(1–2), 7–15.

• Moré, M.I., & Kenley, D. (2014). Safety and metabolism of AOD9604: a research review. Journal of Endocrinology and Metabolism, 4(3), 64–77.

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