The topic of this article will revolve around the AOD 9604 peptide and analysis of its potential effects on metabolism in vitro. If this topic sparks your curiosity, keep reading. Let’s dive right in!
Studies suggest human growth hormone amino acids 177–191 are the building blocks of the peptide known as AOD9604, which also has a tyrosine residue at its N-terminus. It’s been hypothesized to have a lipolytic effect similar to growth hormones without diabetogenic risks.
Research suggests after incubating AOD9604 in serum and urine, six possible metabolites of the peptide were discovered. Serum metabolite quantification suggested one very stable metabolite, the amino acid sequence CRSVEGSCG, which is far less likely to degrade than the parent chemical or the other metabolites. An expanded detection window may be possible with screening for AOD9604 and the stable metabolite. [i]
AOD 9604 and Lipid Metabolism
Researchers speculate that when given over an extended period, human GH (hGH) and a lipolytic fragment (AOD9604) produced from its C-terminus may cause weight loss and boost lipolytic sensitivity in mice. The beta-adrenergic pathway, and more specifically beta(3)-adrenergic receptors (beta(3)-AR), may play a role in this. Here, we detail the effects of chronic hGH and AOD9604 on weight and fat percentage after 14 days in obese mice. Studies suggest the primary lipolytic receptor in adipose tissue, beta(3)-AR RNA, may be upregulated, consistent with researchers’ findings. Importantly, both hGH and AOD9604 have been speculated in research to restore beta(3)-AR RNA levels in obese mice to levels similar to those in lean animals, which was previously thought impossible.
Research suggests long-term hGH plus AOD9604 failed to cause the change in body weight and increase lipolysis seen in wild-type control mice, suggesting the relevance of beta(3)-AR. While AOD 9604 did not appear to increase energy expenditure or fat oxidation in beta(3)-AR knock-out mice throughout the long term of the study, it appeared to do so in a short-term trial. In conclusion, the research suggests that although hGH and AOD 9604 may raise beta(3)-AR expression, contributing to increased lipolytic sensitivity, neither compound’s lipolytic activities are mediated directly via the beta(3)-AR. [ii]
In addition, plasma glycerol levels were measured to assess lipolytic activity in this investigation. The results suggest Glycerol levels appeared elevated in WT mice after being given AOD 9604 and hGH, suggesting an increase in lipolysis. However, findings suggest AOD 9604 did not impact the 3-KO mouse. Results further suggested that following hGH, plasma glycerol would increase significantly compared to controls, although this rise was much less than in the WT mouse. These results suggest that alpha-3 adrenergic receptors play a critical role in the lipolytic response to AOD 9604 in these animals and are required for the chronic efficacy of AOD 9604 and hGH in fat reduction.
Finally, the acute potential of AOD9604 and a 3-AR agonist (BRL37344) on thermogenesis, fatty acid oxidation, and glucose oxidation were compared between wild-type and 3-KO mice. Studies suggest AOD 9604 or BRL37344 in WT mice may have caused an immediate increase in fat oxidation and energy expenditure without a corresponding increase in glucose oxidation. After 18 minutes, the effect seemed to reach a plateau and stayed the same for the rest of the study. Despite prior ligand binding investigations (11) suggesting that AOD 9604 may not directly interact with the 3-AR, the reaction to the two substances was highly comparable.
Research suggests that although AOD9604 and BRL37344 may boost fat oxidation and energy expenditure in 3-KO mice, AOD 9604 does so more so than BRL37344. Findings suggested that when given AOD 9604, the KO mice did not appear to exhibit reduced glucose oxidation or a sustained increase in fat oxidation and energy expenditure. [iii]
In another research, the metabolic effects of a human growth hormone (hGH) synthetic analog (AOD 9604) on obese Zucker rats have been investigated. Results suggested that rats appeared to have gained over half (50%) of body weight after 19 days of AOD9604 compared to the control group. Findings also suggested lipolytic activity appeared elevated in the fatty tissues of AOD 9604 mice. Using euglycemic clamp methods, researchers suggested that AOD9604 appeared to have no impact on the animals’ insulin sensitivity, in contrast to hGH. These findings raise the possibility that the hGH lipolytic domain analog might be further developed into an agent for mitigating the effects of obesity. [iv]
More study is needed to understand its potential applications in science fully. AOD 9604 for sale online is restricted to usage in research and educational institutes. Remember that none of the substances discussed here are approved for ingestion by humans or animals. Compounds used in scientific research should never be used outside of a laboratory. It is forbidden to make a personal introduction of any type. Sales are restricted to verified professionals and active scientists only. This article’s information is meant only for educational purposes.
References
[i] Cox HD, Smeal SJ, Hughes CM, Cox JE, Eichner D. Detection and in vitro metabolism of AOD9604. Drug Test Anal. 2015 Jan;7(1):31-8. doi: 10.1002/dta.1715. Epub 2014 Sep 10. PMID: 25208511.
[ii] 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.
[iii] 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.
[iv] Mark Heffernan and others, 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, Volume 142, Issue 12, 1 December 2001, Pages 5182–5189, https://doi.org/10.1210/endo.142.12.8522