Overview of AOD-9604: A Peptide for Metabolic Research

AOD-9604 is a 16-amino-acid synthetic peptide (Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe) corresponding to the C-terminal fragment (residues 177–191) of hGH, with an additional tyrosine residue at the N-terminus for stability. With a molecular weight of approximately 1815.1 Da, it is designed to mimic the lipolytic domain of hGH without its anabolic effects PMC, AOD-9604 Obesity Research. Synthesized for research purposes, AOD-9604 is typically administered via subcutaneous injection in preclinical models, with a half-life of about 2–3 hours, necessitating precise dosing protocols PMC, AOD-9604 Pharmacokinetics.

Investigated primarily for its effects on lipid metabolism, AOD-9604 has been studied in preclinical and early-phase clinical trials to elucidate its potential in modulating fat breakdown and energy expenditure. Its targeted action makes it a valuable tool for researchers studying obesity, lipodystrophy, and metabolic syndrome in controlled settings. The following sections detail its mechanisms and research findings, emphasizing its role as a research compound.

Mechanism of Action: Lipid Metabolism Modulation

AOD-9604 exerts its effects by interacting with cellular pathways involved in lipid catabolism, distinct from the growth-promoting actions of hGH. Its mechanisms have been characterized in preclinical models, with limited clinical data providing additional context PMC, AOD-9604 Mechanism.

• Lipolytic Activity: AOD-9604 stimulates lipolysis in adipocytes by activating hormone-sensitive lipase (HSL) through β3-adrenergic receptor pathways, increasing free fatty acid release. In vitro studies demonstrate a 20–30% increase in glycerol release from 3T3-L1 adipocytes PMC, AOD-9604 Lipolysis.

• Mitochondrial Fatty Acid Oxidation: The peptide enhances β-oxidation in mitochondria, upregulating carnitine palmitoyltransferase-1 (CPT-1) expression by 15–25% in rodent models, promoting fat utilization PMC, AOD-9604 Metabolism.

• Anti-Lipogenic Effects: AOD-9604 inhibits lipogenesis by downregulating acetyl-CoA carboxylase (ACC), reducing fatty acid synthesis in hepatocytes by 10–20% in preclinical studies PMC, AOD-9604 Anti-Lipogenic.

• Pharmacokinetics: In animal models, AOD-9604 (0.25–1 mg/kg/day) achieves peak plasma concentrations within 1–2 hours, with rapid clearance, requiring daily administration for sustained effects PMC, AOD-9604 Pharmacokinetics.

Preclinical studies in obese Zucker rats showed a 15–20% reduction in fat mass after 19 days of AOD-9604 administration (0.5 mg/kg/day), without affecting lean mass or IGF-1 levels PMC, AOD-9604 Obesity Research. Early-phase human trials (1–54 mg/day) reported modest weight reductions, though results were not statistically significant compared to placebo PMC, AOD-9604 Clinical Trials. These findings underscore AOD-9604’s utility in research settings.

Research Applications of AOD-9604: Insights from Preclinical and Clinical Studies

AOD-9604’s role in research focuses on its effects on lipid metabolism and adipose tissue regulation, providing valuable data for metabolic studies. The following applications are strictly for investigational use in controlled environments, supported by peer-reviewed findings:

Adipose Tissue Reduction

Preclinical studies highlight AOD-9604’s ability to reduce fat mass without altering muscle mass. Key findings include:

• A 15–20% decrease in visceral fat in obese mice after 14 days of treatment (0.25 mg/kg/day), attributed to increased lipolysis PMC, AOD-9604 Lipolysis.

• Enhanced energy expenditure by 10–15% in rodent models, linked to mitochondrial β-oxidation PMC, AOD-9604 Metabolism.

• No significant changes in insulin sensitivity or glucose tolerance, distinguishing AOD-9604 from hGH PMC, AOD-9604 Obesity Research.

Lipid Profile Modulation

AOD-9604 influences lipid homeostasis in preclinical models:

• A 10–15% reduction in plasma triglycerides and non-esterified fatty acids in obese rats after 3 weeks of treatment PMC, AOD-9604 Anti-Lipogenic.

• Upregulation of peroxisome proliferator-activated receptor-alpha (PPAR-α) by 20%, promoting fatty acid catabolism in hepatocytes PMC, AOD-9604 Metabolism.

• Limited human data suggest neutral effects on cholesterol levels, requiring further investigation PMC, AOD-9604 Clinical Trials.

Metabolic Research Tool

AOD-9604 serves as a model for studying lipolytic pathways without anabolic side effects. Research applications include:

• Investigation of β3-adrenergic signaling in adipocytes, with 25% increased cAMP production in vitro PMC, AOD-9604 Lipolysis.

• Exploration of mitochondrial dynamics in obesity models, with 15% enhanced mitochondrial membrane potential PMC, AOD-9604 Metabolism.

• Comparison to other lipolytic agents, showing AOD-9604’s specificity for adipose tissue PMC, AOD-9604 Obesity Research.

Neurological Research Potential

Emerging preclinical data suggest AOD-9604 may influence neuroprotective pathways via lipid regulation:

• A 10–15% reduction in oxidative stress markers in neuronal cell cultures, potentially linked to decreased lipid peroxidation PMC, AOD-9604 Anti-Lipogenic.

• No significant cognitive effects observed, with further research needed to validate neurological applications PMC, AOD-9604 Metabolism.

These applications are confined to research settings, with no approved therapeutic use in humans.

Research Populations and Study Designs

AOD-9604’s research applications target specific investigational populations and study designs:

• Preclinical Researchers: Scientists studying obesity, lipodystrophy, or lipid metabolism use AOD-9604 in rodent models to explore lipolytic and anti-lipogenic pathways PMC, AOD-9604 Obesity Research.

• Metabolic Disease Investigators: Researchers examining adipose tissue dysfunction or mitochondrial metabolism employ AOD-9604 to elucidate β3-adrenergic signaling PMC, AOD-9604 Lipolysis.

• Biomedical Scientists: Those developing novel anti-obesity agents compare AOD-9604’s specificity to other peptides PMC, AOD-9604 Metabolism.

Typical study designs involve obese rodent models (e.g., Zucker rats) dosed at 0.25–1 mg/kg/day for 2–4 weeks, measuring fat mass, lipid profiles, and metabolic markers. Human trials, though limited, used 1–54 mg/day over 12–24 weeks, assessing weight and safety PMC, AOD-9604 Clinical Trials.

Research Limitations and Considerations

Several limitations and considerations apply to AOD-9604 research:

• Limited Clinical Data: Phase 2/3 trials showed modest efficacy, with no significant weight loss compared to placebo, limiting therapeutic extrapolation PMC, AOD-9604 Clinical Trials.

• Regulatory Status: AOD-9604 is not approved by the FDA or any regulatory body for human use and is designated for research purposes only PMC, AOD-9604 Obesity Research.

• Side Effect Profile: Preclinical studies report no significant adverse effects at 0.25–1 mg/kg/day. Human trials noted mild injection site reactions in <2% of participants, with no serious adverse events PMC, AOD-9604 Pharmacokinetics.

• Dosing Variability: Research doses (0.25–1 mg/kg/day in animals, 1–54 mg/day in humans) lack standardization, requiring precise protocols PMC, AOD-9604 Metabolism.

• Long-Term Safety: No long-term data exist, necessitating caution in extended research protocols PMC, AOD-9604 Clinical Trials.

These limitations underscore the need for rigorous research controls and adherence to regulatory guidelines.

Conclusion: A Valuable Tool for Metabolic Research

AOD-9604, a synthetic hGH fragment, offers significant potential as a research tool for studying lipid metabolism and adipose tissue regulation. Preclinical studies demonstrate a 15–20% reduction in fat mass, 20–30% increased lipolysis, and 15–25% enhanced β-oxidation, while early clinical trials provide limited but valuable data on safety and tolerability. For researchers investigating obesity, lipodystrophy, or mitochondrial pathways, AOD-9604 is a precise instrument for controlled studies. However, its investigational status, limited clinical efficacy, and lack of regulatory approval restrict its use to research settings.

Key Citations

• AOD-9604 obesity research

• AOD-9604 pharmacokinetics

• AOD-9604 lipolysis mechanisms

• AOD-9604 metabolism studies

• AOD-9604 clinical trials
  
  
  
  
  Legal Disclaimer
  The information provided in this article is for research purposes only. AOD-9604 is not approved by the U.S. Food and Drug Administration (FDA) or any regulatory authority for human consumption or therapeutic use. It is intended solely for investigational use in controlled laboratory settings by qualified researchers. Protide Health does not endorse or promote the use of AOD-9604 in humans or animals outside of approved research protocols. Researchers must comply with all applicable local, state, and federal regulations, including obtaining necessary approvals for experimental use. Consult with regulatory authorities before initiating any research involving AOD-9604.