AOD-9604

What is AOD-9604?

AOD-9604 (Advanced Obesity Drug) represents molecular surgery on growth hormone. Australian researchers at Monash University identified the 176-191 C-terminal region as responsible for GH's lipolytic effects, then added stabilizing modifications to create a fragment that stimulates lipolysis without growth hormone receptor binding. The result: a peptide that mimics GH's fat-mobilizing properties while completely avoiding effects on growth, glucose metabolism, or IGF-1—a clean separation impossible with full-length GH.

This selective action makes AOD-9604 invaluable for dissecting GH's metabolic effects. Researchers can investigate lipolytic signaling mechanisms, study adipocyte beta-oxidation, and explore growth hormone's metabolic functions without the confounding variables of receptor-mediated GH actions. The fragment's mechanism—potentially involving non-receptor-mediated pathways—remains an active area of investigation.

Mechanism of Action

AOD-9604 represents the isolated C-terminal fragment of human growth hormone (amino acids 176-191) that retains lipolytic activity while lacking GH receptor binding capability. The peptide appears to stimulate lipolysis through β3-adrenergic receptor activation on adipocytes rather than through the JAK-STAT pathway used by full-length GH. Studies suggest AOD-9604 may mimic the conformational structure of a GH region that interacts with β3-AR, triggering adenylyl cyclase activation, cAMP elevation, and protein kinase A-mediated phosphorylation of hormone-sensitive lipase (HSL) and perilipin.

This mechanism explains the selective metabolic effects: by bypassing GH receptor, AOD-9604 avoids GH-mediated effects on IGF-1 production, glucose metabolism, and cell proliferation. The peptide demonstrates preferential action on abdominal adipocytes which express higher β3-AR density. Additionally, AOD-9604 may inhibit lipogenesis by reducing acetyl-CoA carboxylase activity. The tyrosine addition at the N-terminus (absent in native HGH 176-191) enhances stability and may contribute to receptor interaction. Unlike full GH, AOD-9604 shows no effects on blood glucose, insulin levels, or growth, making it a selective tool for studying GH-independent lipolytic pathways.

Key Research Findings

• Reduces body fat by 50% in genetically obese mice after 14 days treatment without affecting lean mass or food intake [Heffernan et al., 2001]
• Demonstrates 155% increase in lipolytic activity in isolated adipocytes at 10 μM concentration vs vehicle control [Ng et al., 2000]
• Shows no IGF-1 elevation or glucose/insulin changes across dose range 1-10 mg/day in phase 2 trials [Stenlof et al., 2000]
• Reduces visceral adipose tissue by 31% vs 12% placebo in 12-week obesity trial [Heffernan et al., 2005]
• Activates β3-adrenergic receptor signaling with EC50 of 4.2 μM in transfected cell lines [Ng et al., 2000]

Research Applications

• Lipolysis mechanism research
• GH fragment biology
• Lipid metabolism studies
• Adipocyte signaling independent of GH receptor
• Selective metabolic pathway activation
• Non-receptor GH effects

Reconstitution & Use

Reconstitute with bacteriostatic water for laboratory use. For detailed reconstitution instructions and concentration ratios for your specific research application, see our reconstitution guide.

Storage & Handling

Store lyophilized at -20°C. Upon reconstitution with bacteriostatic water, maintain at 2-8°C and use within 30 days. The modifications provide enhanced stability compared to unmodified HGH fragments.