AOD 9604 Peptide

AOD 9604 is a synthetic analog of growth hormone (hGH) designed to support research into obesity and weight loss. It is derived from the C-terminal fragment of hGH (amino acids 176–191), also known as GH Fragment 176–191. A tyrosine residue replaces the first amino acid at the N-terminus to improve peptide stability.(1)

This fragment is considered the lipolytic region of hGH. Different regions of the full 191–amino acid hormone have distinct functions—for example, the N-terminal region may influence insulin activity, while amino acids 108–129 have mitogenic effects.(2)

Overview

Developed in the 1990s, AOD 9604 was studied for anti-obesity properties similar to hGH. Research suggests it may influence lipolysis—the breakdown of stored fats (triglycerides) into glycerol and free fatty acids for energy.

The peptide appears to affect fat cells and lipolytic pathways, potentially increasing sensitivity to lipolytic signals. Studies indicate it may elevate expression of beta(3)-adrenergic receptors (beta(3)-AR), key receptors involved in fat metabolism. While increased receptor expression is observed, AOD 9604 may not act directly through beta(3)-AR.

Unlike full hGH, AOD 9604 may stimulate fat metabolism without increasing Insulin-like Growth Factor 1 (IGF-1), which is associated with many of hGH’s systemic effects.

Chemical Makeup

• Molecular Formula: C78H123N23O23S2

• Molecular Weight: 1815.12 g/mol

• Other Name: Tyr-hGH Fragment 177–191

Research and Clinical Studies

AOD 9604 Peptide and Lipolytic Activity

Animal studies in obese mice showed that AOD 9604 administration over 14 days reduced body weight and fat mass. These changes correlated with increased beta(3)-AR expression. However, further studies in mice lacking these receptors suggested that the peptide’s effects may also involve increased energy expenditure and fat oxidation.(1)

In a 2000 study on obese Zucker rats, daily administration for 19 days resulted in over 50% greater weight reduction compared to placebo. Increased lipolysis was observed without impairing insulin sensitivity.(3)

AOD 9604 Peptide and Obesity

In 2004, clinical trials observed the actions of the peptide in 300 obese subjects who were given the peptide for 12 weeks. The rate of weight loss remained consistent throughout the study period. The trial results noted minor improvement exhibited in the subjects’ cholesterol profiles and glucose tolerance levels.⁽⁴⁾

AOD 9604 Peptide and Cell Regeneration

Additional research was conducted to study the regenerative potential of the peptide. In 2015, 32 white rabbits were divided into four groups of eight, and each group was given a placebo, AOD 9604, hyaluronic acid, or a combination of AOD 9604 and hyaluronic acid for 4 to 7 weeks. After the study, these rabbits were assessed morphologically and histopathologically to determine the degree of cartilage degeneration. It was concluded that rabbits given the combination of AOD 9604 with hyaluronic acid apparently exhibited the least degeneration. Thus, it was suggested by the researchers that AOD 9604 might exhibit potential to enhance cartilage regeneration and cartilage repair in some capacity.⁽⁵⁾

This may be due to the potential role of AOD 9604 in cellular differentiation processes and, potentially, in the synthesis of proteins important for tissue repair. According to an in vitro study, AOD 9604 may possibly enhance the differentiation of adipose mesenchymal stem cells into bone⁽⁵⁾. These stem cells, which are typically found within fat tissue, may have the potential to evolve into various cell types. It has been hypothesized that under the influence of AOD 9604, these stem cells may show a predisposition to differentiate into bone cells. Moreover, when the research was conducted on isolated bovine chondrocytes, it appeared that there might be an increased production of proteoglycan and collagen. Chondrocytes are cells believed to be found within cartilage tissue, and they possibly play a role in producing and maintaining the extracellular matrix, which consists of components like collagen and proteoglycans. It is posited that the presence of AOD 9604 could stimulate these chondrocytes to produce more of these vital components. The study also hints at the idea that AOD 9604 might promote the differentiation of myoblasts into C2C12 cells. Myoblasts are thought to be precursor muscle cells, and C2C12 cells are a type of murine model muscle cell line. From what the study suggests, AOD 9604 may assist in the transition of these precursor cells into a more mature form. The research seems to underline the potential role AOD 9604 might have in processes connected to the repair of bone, cartilage, and muscle tissues.

AOD 9604 and Research in Cancer Cells

The peptide may be able to bind (target) tumor-related proteins to enhance tumor drug accumulation and local cytotoxicity.⁽⁶⁾ The hGH fragment AOD 9604 may potentially play a pivotal role in cancer cell research, as it has been observed to enhance the anticancer efficacy of doxorubicin, a commonly recognized chemotherapeutic agent. One study utilized chitosan nanoparticles, a biocompatible and biodegradable polymer, as a carrier for doxorubicin and AOD 9604.⁽⁶⁾ The research team hypothesized that AOD 9604 possibly enhanced the doxorubicin binding to multiple breast cancer cell protein targets, thereby exhibiting greater anti-proliferative activity against the MCF-7 breast cancer cell line compared to chitosan loaded with doxorubicin alone. This suggests that AOD 9604 may potentially augment the anti-cancer potency of doxorubicin while possibly minimizing unintended actions associated with non-target tissue exposure. In conclusion, multiple clinical studies have suggested that the peptide may significantly induce lipolysis and possibly prevent lipogenesis by mimicking natural hGH.

AOD 9604 is available for research and laboratory purposes only.