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AOD 9604 Peptide: Research in Lipolysis, Cell Regeneration, and Cancer

AOD 9604 Peptide: Research in Lipolysis, Cell Regeneration, and Cancer Feb 21, 2024 Originating from the modification of the growth hormone’s last 16 amino acids (176-191), this peptide, alternatively known as GH Fragment 176-191 or AOD 9604, has garnered atte

By Recovery & Performance Peptides Editorial Team

AOD 9604 Peptide: Research in Lipolysis, Cell Regeneration, and Cancer

Feb 21, 2024

Originating from the modification of the growth hormone’s last 16 amino acids (176-191), this peptide, alternatively known as GH Fragment 176-191 or AOD 9604, has garnered attention for its distinctive potential. The incorporation of a tyrosine residue at the N-terminus further contributes to the peptide’s stability, as suggested by researchers.(1)

This lipolytic fragment of hGH reportedly exhibits varied potentials within its 191 amino acid structure. Notably, studies highlight the insulin-potentiating action associated with the N-terminal region, while amino acids 108-129 elicit high mitogenic responses.(2)

AOD 9604’s designation as a modified version of fragment 176-191 positions it to potentially induce lipolysis, possibly without significant impacts on insulin and IGF-1 levels, mitigating potential risks associated with glucose intolerance and diabetes. Moreover, the structural similarity between AOD 9604 and HGH appears to minimize the likelihood of antibody formation.(3)

Fig 1. AOD 9604 Chemical Structure

Mechanism of Action

The mechanism of action of AOD 9604 peptide appears to involve its synthetic derivation from growth hormone (hGH), which is considered to facilitate the modulation of metabolic processes.

AOD 9604 reportedly operates by eliciting lipolysis and inhibiting lipogenesis, thus promoting the breakdown of fat and impeding the formation of new fat stores. Notably, these effects are speculated to be achieved through oxidative pathways and may occur independently of the hGH receptor.(1)

AOD 9604 peptide appears to exert a weight-reducing potential without altering caloric intake or appetite and without adversely affecting insulin sensitivity. Research findings indicate that this peptide may potentially facilitate the release of fat from adipose tissue while concurrently mitigating the accumulation of new fat deposits. Such actions underscore the potential of AOD 9604 in research related to adiposity and its associated metabolic disturbances.

AOD 9604 and Lipolysis Research

Early investigations into the effects of AOD 9604 peptide involved studies conducted on obese mice over a period of 14 days. The findings of these studies reported a significant decrease in the research models’ body weight and adipose tissue accumulation subsequent to the intervention. Concurrently, an elevation in the levels of key lipolytic receptors, specifically beta(3)-adrenergic receptors (β3-AR), within adipocytes was observed. Such findings suggest a direct correlation between the reduction in adiposity and the augmented expression of β3-AR.

Notably, the lipolytic activity exhibited by AOD 9604 peptide appears analogous to that of growth hormone (hGH), implying a potential shared mechanism wherein both agents exhibit the capacity to upregulate suppressed lipolytic receptor levels in obese mice relative to their lean counterparts. To discern whether the lipolytic effects of AOD 9604 are solely contingent upon enhanced β3-AR expression, further investigations were conducted utilizing mice with genetically ablated lipolytic receptors. Subsequent analyses suggested that AOD 9604 peptide may exert a lipolytic action through mechanisms involving heightened energy expenditure and enhanced fat oxidation(1).

In a subsequent study conducted in 2000, the efficacy of AOD 9604 peptide was evaluated in obese Zucker rats through daily exposure over 19 consecutive days. Results from this investigation indicated that the peptide “reduced over 50% body weight gain of the animals in comparison with the control.” Further observation indicated heightened lipolytic activity within the adipose tissues of rats receiving AOD 9604 peptide, accompanied by an absence of notable disruptions in insulin sensitivity.(4)

AOD 9604 and Cellular Regeneration Research

In a study conducted in 2015, 32 white rabbits were divided into four groups of eight, each receiving either a placebo, AOD 9604 peptide alone, hyaluronic acid alone, or a combination of AOD 9604 and hyaluronic acid for a duration ranging from 4 to 7 weeks. Subsequent morphological and histopathological evaluations of the rabbits aimed to assess the extent of cartilage degeneration post-exposure. The findings indicated that rabbits exposed to the combination of AOD 9604 and hyaluronic acid appeared to have exhibited the least degeneration in cartilage tissue.

The purported mechanism underlying these regenerative effects may involve the modulation of cellular differentiation processes and the synthesis of proteins crucial for tissue repair. In vitro investigations have hinted at the potential of AOD 9604 to promote the differentiation of adipose-derived mesenchymal stem cells into osteogenic lineages, potentially facilitating bone regeneration. Additionally, experiments conducted on isolated bovine chondrocytes revealed an upregulation in the production of proteoglycans and collagen, fundamental components of the extracellular matrix essential for cartilage integrity.(6)

Moreover, data suggests that AOD 9604 may stimulate the differentiation of myoblasts into mature muscle cells, highlighting its putative role in muscle tissue repair processes.

AOD 9604 and Cancer Research

AOD 9604 may potentially support the anti-cancer efficacy of certain chemotherapeutic compounds. One study employed chitosan nanoparticles as carriers for both the chemotherapy compound and AOD 9604 peptide, hypothesizing that AOD 9604 may potentially facilitate the binding of the compound to multiple protein targets within breast cancer cells, thereby augmenting its anti-proliferative effects.

The study reportedly states that “dual-loaded Chitosan nanoparticles demonstrated greater anti-proliferative activity against a breast cancer cell line (MCF-7) than doxorubicin-loaded Chitosan”.(7) These findings suggest the potential of AOD 9604 in enhancing the efficacy of conventional anticancer agents while potentially minimizing off-target effects, warranting further exploration in cancer-related research.

Conclusion

The AOD 9604 peptide has been widely researched on a global scale for its potential lypolytic action, although the peptide has been suggested to enact other impacts outside of any metabolic activity. Researchers have studied the action of the peptide under contexts related to cancer cell proliferation and chemotherapy, tissue and cartilage repair, and muscle cell development.

NOTE: These products are intended for laboratory research use only. This peptide is not intended for personal use. Please review and adhere to our Terms and Conditions before ordering.

References:

Heffernan M, Summers RJ, Thorburn A, Ogru E, Gianello R, Jiang WJ, Ng FM. 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 Dec;142(12):5182-9. doi: 10.1210/endo.142.12.8522. PMID: 11713213. https://pubmed.ncbi.nlm.nih.gov/11713213/

MORé, M., KENLEY, D.. Safety and Metabolism of AOD9604, a Novel Nutraceutical Ingredient for Improved Metabolic Health. Journal of Endocrinology and Metabolism, North America, 4, jun. 2014 https://www.jofem.org/index.php/jofem/article/view/213/278.

STIER, H., VOS, E., KENLEY, D.. Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans. Journal of Endocrinology and Metabolism, North America, 3, apr. 2013. https://www.jofem.org/index.php/jofem/article/view/157

Ng FM, Sun J, Sharma L, Libinaka R, Jiang WJ, Gianello R. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Horm Res. 2000;53(6):274-8. doi: 10.1159/000053183. PMID: 11146367. https://pubmed.ncbi.nlm.nih.gov/11146367/

Medical and Life Sciences, Obesity drug codenamed AOD 9604 highly successful in trials, 16 December 2004. https://www.news-medical.net/news/2004/12/16/6878.aspx

Dong Rak Kwon and GI Young Park, Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model, Annals of Clinical and Laboratory Science, Volume 45, July-August 2015. https://pubmed.ncbi.nlm.nih.gov/26275694/

Habibullah, M. M., Mohan, S., Syed, N. K., Makeen, H. A., Jamal, Q. M. S., Alothaid, H., Bantun, F., Alhazmi, A., Hakamy, A., Kaabi, Y. A., Samlan, G., Lohani, M., Thangavel, N., & Al-Kasim, M. A. (2022). Human Growth Hormone Fragment 176-191 Peptide Enhances the Toxicity of Doxorubicin-Loaded Chitosan Nanoparticles Against MCF-7 Breast Cancer Cells. Drug design, development and therapy, 16, 1963–1974. https://doi.org/10.2147/DDDT.S367586

Image source: Therapeutic Drug Database: https://idrblab.net/ttd/data/drug/details/D0O7XO

Dr. Marinov

Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.

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CONNECTED / MODULES

Post-session references

Selected from shared article topics. Source links are retained where available.

01

Handling & safety lane

Source-derived education, not individual medical guidance or an instruction to dose.

DOSAGE SOURCE

Dosing in a Research Context

Because AOD-9604 is not an approved medicine, there is no established therapeutic dose, and the figures that circulate come from the historical trial protocols and from research-chemical convention rather than from any regulatory label. This section is descriptive and strictly educational, not a usage recommendation. The human efficacy trials used oral AOD-9604, with dose arms spanning roughly 0.25 mg to 30 mg once daily across the two studies.3 A striking and under-appreciated feature of the trial data is that the lower doses (around 1 mg) tended to perform at least as well as the higher ones — an inverted or flat dose-response that is unusual for a drug thought to act through a straightforward receptor-mediated pathway, and that in itself raises questions about how reliably the compound was doing what it was supposed to do. Oral peptide delivery is also notoriously inefficient, since the gut degrades peptides; the fact that development used an oral formulation complicates any attempt to reason from trial doses to the subcutaneous injection favored in contemporary research settings. In non-clinical and research-chemical contexts today, AOD-9604 is typically encountered as a lyophilized powder reconstituted for subcutaneous use, and the microgram-per-injection figures quoted by vendors (commonly a few hundred micrograms) bear no validated relationship to the oral milligram doses used in the actual efficacy trials. This is a crucial honesty point: no one has run a properly po…
02

Question drills

Open a question for its connected answer.

01What is AOD-9604?+

AOD-9604 is a modified form of human growth hormone (HGH), namely its C-terminus region. Specifically, it’s a 16–amino acid fragment consisting of residues 176–191, which in lay terms means: It’s a synthetic part of a hormone that, in adults, helps to maintain metabolism and normal body structure. 1 It originates from a section of the HGH molecule that appears to promote fat breakdown and prevent the conversion of fatty acids to stored triglycerides 2 3 A Melbourne-based biotech company called Metabolic Pharmaceuticals originally developed AOD-9604 as an a nti- o besity d rug — hence its name — but modified it in such a way as to impart HGH’s more desirable effects while leaving aside the potentially adverse aspects. In particular, AOD-9604 does not stimulate the production of insulin-growth factor 1 (IGF-1), as HGH does, and thus should not increase one’s risk of type 2 diabetes or tumorigenesis, as HGH can. 4 5 It’s primarily selective for fat loss. Another profound characteristic of AOD-9604 is its oral bioavailability, which places it among the relatively few therapeutic peptides that can be administered by either mouth or needle. 6 Metabolic Pharmaceuticals halted further development of AOD-9604 in 2007. Two years later, it licensed AOD-9604 to another Melbourne biotech entity, Phosphagenics Limited, for use as a transdermal cosmetic preparation to reduce cellulite and subcutaneous fat.

SOURCE / www.innerbody.com ↗
03

Evidence cooldown

Research context and source excerpts for a slower second read.

RESEARCH

AOD 9604 Peptide and Other Research Objectives

Researchers have also explored the potential of AOD 9604 in models of osteoarthritis and its potential actions on tumor cells. For instance, one trial modeled AOD 9604 with and without hyaluronic acid (HA) in a collagenase-induced osteoarthritis model.[7] The morphological and histopathological scores, which indicate the extent of cartilage degeneration, were apparently lower in the AOD 9604 groups. The combination of AOD 9604 and HA indicated potentially synergistic actions. Specifically, the AOD 9604 peptide and HA group suggest reduced signs of cartilage degradation compared to the other groups. This suggests that AOD 9604 peptide might influence cartilage through mechanisms similar to growth hormone by promoting proteoglycan and collagen production, though in a way that does not involve IGF-1. HA, believed to act as a chondroprotective agent, may also have supported these relevant impacts, possibly supporting the residence time of AOD 9604 in the joint or contributing to its bioactive properties. The study emphasized that while AOD 9604 suggested promise in supporting cartilage regeneration, the exact mechanisms by which it exerts these impacts are not well understood. AOD 9604 peptide has displayed promising potential in increasing the potential of anti-cancer cell agents like doxorubicin’s ability to bind to critical breast tumor cell receptors such as the progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2).[8] These receptors are pivotal in the progression of these tumor cells, and better-supported binding suggests that doxorubicin may more impactfully target and interfere with cancer cell functions. By loading both AOD 9604 and doxorubicin into Chitosan nanoparticles, the study achieved a delivery system that supports doxorubicin’s potential. In vitro studies on MCF-7 breast tumor cells indicated that the dual-loaded nanoparticles were more impactful in killing these cells than nanoparticles containing doxorubicin alone, as observed in data that displays comparatively lower IC50 values. The presence of AOD 9604 peptide may support how tumor cells take up doxorubicin or alter how similar agents interact inside the cells, leading to increased tumor cell death. By supporting delivery specifically to tumor cells, AOD 9604 may help reduce the off-target impacts of doxorubicin, minimizing damage to functional cells. Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing. Bodily introduction of any sort is strictly prohibited by law. All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

POTENTIAL BENEFITS

Potential Benefits of AOD 9604 (Based on Existing Research)

Available findings must be interpreted cautiously, as human evidence is limited and often early-phase.
05

Product & matchup locker

Linked catalog and comparison files.

Comparison

Targeted Fat Metabolism Versus Target Fat and Stubborn Fat Claims

AOD-9604 is sometimes described online as targeting fat cells or stubborn fat, but published evidence does not establish selective regional fat loss in patients. Preclinical work …

Comparison

Claim by Claim: Animal Evidence vs Human Evidence

Every claim on a typical AOD 9604 sales page traces back to one of these rows. Stimulates lipolysis Yes, obese Zucker rats and ob/ob mice (Ng 2000; Heffernan 2001) Not measured as…

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