The modified peptide AOD 9604 was first created as a byproduct of research to potentially reduce obesity. HGH peptide 176–191 has its N-terminus altered by adding a tyrosine residue. Researchers have speculated that AOD 9604’s action method is limited to increasing lipolysis, which connects the synthetic chemical to studies of obesity.[i]
Studies so far suggest no effect of the peptide on insulin or IGF1 levels, suggesting it may not promote diabetes development or produce glucose intolerance in test animals; however, further research is needed to confirm this.[ii]
AOD 9604 Peptide Structure
Researchers speculate that several HGH subunits may each have unique features and produce various effects in murine test models. It has been hypothesized that the hormone’s potential to burn fat is mediated only by its last 15 amino acids [iii]. HGH 177-191 was a fragment of growth hormone that was later changed by the addition of tyrosine to form AOD 9401. A fragment of AOD 9604 consisting of 16 amino acids was created due to this change.[iv] Interestingly, the authors note that “AOD 9604 does not interact with the hGH receptor.” This change may have rendered fragment 176–191 of growth hormone (HGH) more stable than similar peptides.
AOD 9604 Peptide: Mechanism of Action
Extensive research with AOD 9604 has been conducted on mouse models, often using rather high compound quantities.[v] The weight loss from these tests averaged 50%. It is worth noting, however, that the fragment doesn’t seem to have any other putative HGH effects, such as elevating IGF-1 (insulin-like growth factor-1), insulin resistance, or cell proliferation.
So, the chemical may lack the growth hormone-like properties of retaining muscle mass and increasing protein synthesis. However, research suggests that AOD 9604 may induce weight reduction by processes similar to HGH, perhaps resulting in the secretion of fatty acids from adipose cells via the activation of numerous cellular pathways. In addition, the peptide has been hypothesized to influence lipases, an enzyme family that blocks fat re-uptake by fatty tissues.[vi]
Research suggests that AOD 9604 does not seem to affect natural HGH synthesis and does not seem to work as a growth hormone secretagogue, which is important to keep in mind. It also does not seem to enhance appetite or change how much food intake was observed with the animals. Different results have been observed in lean and obese murine models when comparing AOD 9604 with HGH.[iv]
Findings imply that HGH may improve lean body mass compared to lean mice with AOD 9604 or a placebo. Therefore, scientists have wondered whether HGH AOD 9604 may help expand muscle cells and foster muscular hypertrophy. However, both HGH and AOD 9604 show promise as weight-loss agents in obese mouse models. The hypothesized noted that the loss of fatty tissue seemed to be 40% more in the HGH group than in the AOD 9604 group. Because of this, it seems from the study that the capacity of AOD 9604 to stimulate the release of lipids from adipose cells may be less than that of HGH.[vii]
Investigations purport that both hGH and AOD 9604 may possibly act to raise 3-AR expression, which may contribute to increased lipolytic sensitivity, but the authors of the study note that “the lipolytic actions of both hGH and AOD 9604 are not mediated directly through the 3-AR.” The hypothesized effect of growth hormone on insulin resistance may encourage a larger release of lipids from adipose cells.
Reducing glucose absorption may lead to increased fat utilization by cells. However, researchers speculate that AOD 9604 does not seem to promote insulin resistance like the other fragments appear to. Mouse models have not verified the properties of AOD 9604, although anecdotal data suggests it may support the declination in cholesterol and increase in insulin sensitivity.
AOD 9604 Peptide and Obesity
Research studies of AOD 9604, a peptide comparable to HGH, have been initiated to explore the peptide’s role within the context of obesity. When presented, the peptide seemed to cause consistent weight reduction over 12 weeks in a phase 2b clinical trial involving 300 obese test models in Australia.[viii] Weight loss rates were constantly compared to those of the placebo group, and the rates seemed stable throughout the research. The lack of resistance shown by this finding suggests that the peptide’s effects if maintained, might have a significant outcome. Research in this field is continuing.
Researchers have also turned to mouse models to investigate the mechanism of AOD 9604 further. White adipose tissue (fat) is thought to have -3-adrenergic receptors, and it was hypothesized that AOD 9604 may bind to and activate these receptors. Upon binding to its corresponding receptors, the peptide may initiate downstream signaling that drives fat cells out of storage and into an active, metabolically active state. Fat loss, maybe due to apoptosis of the white adipose tissues, was seen in mice with a genetic mutation in -3-adrenergic receptors.
AOD 9604 and the Heart
Findings imply that by increasing fat mobilization and decreasing obesity, AOD 9604 may indirectly enhance heart health. Obesity is associated with an increased risk of heart disease. Researchers have postulated other methods through which the peptide may enhance cardiac conditions beyond its stated primary potential of reducing fat load. These mechanisms may enhance overall metabolism and benefit heart function independently of -3 adrenergic receptors.[ix
Buy AOD-9604 if you are a researcher interested in further studying this peptide in your contained lab environment.
References
[i] Ng, F. M., Sun, J., Sharma, L., Libinaka, R., Jiang, W. J., & Gianello, R. (2000). Metabolic studies of a synthetic lipolytic domain (AOD 9604) of human growth hormone. Hormone research, 53(6), 274–278. https://doi.org/10.1159/000053183
[ii] Cox, H. D., Smeal, S. J., Hughes, C. M., Cox, J. E., & Eichner, D. (2015). Detection and in vitro metabolism of AOD 9604. Drug testing and analysis, 7(1), 31–38. https://doi.org/10.1002/dta.1715
[iii] Ng, F. M., Jiang, W. J., Gianello, R., Pitt, S., & Roupas, P. (2000). Molecular and cellular actions of a structural domain of human growth hormone (AOD9401) on lipid metabolism in Zucker fatty rats. Journal of molecular endocrinology, 25(3), 287-298.
[iv] Heffernan, M. A., Thorburn, A. W., Fam, B., Summers, R., Conway-Campbell, B., Waters, M. J., & Ng, F. M. (2001). Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 25(10), 1442–1449. https://doi.org/10.1038/sj.ijo.0801740
[v] Ng, F. M., Sun, J., Sharma, L., Libinaka, R., Jiang, W. J., & Gianello, R. (2000). Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Hormone research, 53(6), 274–278. https://doi.org/10.1159/000053183
[vi] Kopchick, J. J., Berryman, D. E., Puri, V., Lee, K. Y., & Jorgensen, J. O. (2020). The effects of growth hormone on adipose tissue: old observations, new mechanisms. Nature para pharma reviews Endocrinology, 16(3), 135-146.
[vii] Heffernan, M., Summers, R. J., Thorburn, A., Ogru, E., Gianello, R., Jiang, W. J., & Ng, F. M. (2001). The Effects of Human GH and Its Lipolytic Fragment (AOD9604) on Lipid Metabolism Following Chronic Treatment in Obese Mice andβ 3-AR Knock-Out Mice. Endocrinology, 142(12), 5182-5189.
[viii] Bray, G. A., & Greenway, F. L. (2007). Pharmacological treatment of the overweight patient. Pharmacological reviews, 59(2), 151–184. https://doi.org/10.1124/pr.59.2.2
[ix] Heffernan, M., Summers, R. J., Thorburn, A., Ogru, E., Gianello, R., Jiang, W. J., & Ng, F. M. (2001). The effects of human GH and its lipolytic fragment (AOD 9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology, 142(12), 5182–5189. https://doi.org/10.1210/endo.142.12.8522
