Frag 176-191 Peptide: Metabolic Modulation and Regenerative Potential

Fragment 176-191, which scientists may also refer to as hGH Frag 176-191, tyr-hGH 177-191, or AOD-9604, is a synthetic peptide derived from the hGH. It comprises the last 16 amino acids of the hGH molecule, a region hypothesized to be its primary “lipolytic fragment”. This segment is speculated to be associated with promoting the breakdown of adipose tissue and mobilizing lipids from fat cells. To support peptide stability, tyrosine replaces the first amino acid in its sequence, giving rise to the alternative designation tyr-hGH 177-191.⁽¹⁾ Researchers have explored the potential role of this peptide in regulating fat metabolism and have historically drawn parallels to hGH’s proposed catabolic impacts on stores of adipose tissue.

Image: Chemical structure of Frag 176-191 Peptide

Researchers have suggested that Frag 176-191 may interact with beta-3 adrenergic receptors (ß3-AR), which may stimulate fat breakdown in adipose tissue and promote thermogenesis in skeletal muscle cells. In experimental studies involving murine models with excess stores of adipose tissue, exposure of research models to this peptide over two weeks appeared to correlate with weight reduction and decreased murine model mass. Researchers went on to tentatively suggest a link to an increase in ß3-AR RNA expression. This type of link may suggest a potential modulation of the beta-adrenergic signaling pathway.

Interestingly, even in murine models with impaired lipolytic receptors, a reduction in stores of adipose tissue was observed, indicating that the peptide’s mechanisms may extend beyond direct receptor activation. Potential alternate pathways might involve supporting energy expenditure and fat oxidation, though these remain speculative and warrant further scientific investigation.⁽²⁾ The peptide’s stability is believed to be supported by the addition of tyrosine at its N-terminus, which may increase resistance to enzymatic degradation. Additionally, the endogenously occurring disulfide bridge between cysteine residues in the peptide structure might further contribute to its structural integrity. This supports past research that suggests the peptide’s persistence in challenging environments such as the gastrointestinal tract.⁽³⁾⁽⁴⁾

 

Research

Frag 176-191 Peptide and Adipocyte Function

Frag 176-191 is hypothesized to influence adipocyte metabolism through multiple molecular pathways, potentially including the upregulation of beta-3 adrenergic receptors (β3-AR). Preliminary research appears to suggest that the peptide may support the transcriptional activity of β3-AR genes. Researchers believe that the peptide may contribute in some way to increased mRNA expression and subsequent protein synthesis. Elevated receptor density on adipocyte membranes may heighten cellular sensitivity to endogenous catecholamines such as adrenaline, which are thought to engage β3-AR and promote lipolysis directly.

Additionally, Frag 176-191 might activate supplementary intracellular signaling cascades that facilitate fat breakdown. This might involve the upregulation of enzymes crucial to lipolysis or modulation of secondary messengers that amplify lipolytic responses. Though its precise mode of action remains under investigation, these mechanisms present a theoretical basis for its proposed fat-reducing potential.

A notable study, METAOD005, explored these possibilities in a clinical context. This 12-week trial enrolled 300 research models, divided into six groups: one control and five receiving various concentrations of Frag 176-191. Results indicated that one of the peptide-exposed groups experienced a potential average weight reduction of approximately 5.7 pounds. Furthermore, researchers suggested possible improvements in lipid profiles and glucose tolerance among research models, though these findings remain tentative pending further verification.⁽⁵⁾

Frag 176-191 Peptide and Glycogen Metabolism

In a study examining synthetic hGH peptides,⁽⁶⁾ including Frag 176-191, researchers investigated its potential impacts on glycogen metabolism in murine models with normal physiological function. Following peptide introduction, a modest increase in blood glucose and lactate levels was observed. Concurrently, a reduction in the active-to-inactive ratio of glycogen synthase was noted in muscular tissue, adipose tissue, and liver samples, while total glycogen synthase concentrations remained unchanged.

These findings suggest that Frag 176-191 may influence glucose homeostasis by modulating glycogen synthase activity, possibly shifting the enzyme toward its inactive form. This may theoretically suppress glycogen synthesis while supporting glycogenolysis, contributing to elevated circulating glucose and lactate levels. Based on the study, “it was concluded that the peptides acted directly on their target tissues and that the observed hyperlactatemia was the result of the inactivation of pyruvate dehydrogenase. The addition of lactate increased the flux through the gluconeogenic pathway and appeared as glucose because the peptide also inactivated glycogen synthase. Thus, the hyperglycemia produced by hGH 177–199 and related peptides is explicable in terms of a modified Cori Cycle.”⁽⁶⁾

Frag 176-191 Peptide and Cartilage Regeneration

Preliminary research suggests that Fragment 176-191 may exhibit regenerative properties similar to those attributed to hGH beyond its proposed lipolytic impacts. To investigate this, a study utilizing a collagenase-induced knee osteoarthritis model was conducted. Type II collagenase was introduced to induce cartilage damage in the knee joints of experimental models. Following this, subjects were divided into four experimental groups over a 4-7 week period: saline (Group 1), hyaluronic acid (Group 2), Frag 176-191 (Group 3), and a combination of Frag 176-191 and hyaluronic acid (Group 4).⁽⁷⁾

Cartilage regeneration was assessed through morphological and histopathological analyses, alongside evaluations of lameness severity at week 8. Results indicated significantly higher cartilage damage scores in Group 1 compared to Groups 2, 3, and 4. Notably, Group 4 exhibited the lowest damage scores, with significantly reduced lameness duration compared to all other groups. These findings suggest that “AOD9604 [exposure] using ultrasound guidance enhanced cartilage regeneration, and combined AOD9604 and HA [introductions appeared] more effective than HA or AOD9604 … alone.”

 
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:

1. 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. https://pubmed.ncbi.nlm.nih.gov/25208511/
2. 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/
3. Stier, Heike, Evert Vos, and David Kenley. “Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans.” Journal of Endocrinology and Metabolism 3.1-2 (2013): 7-15. https://jofem.org/index.php/jofem/article/view/157
4. Moré, Margret I., and David Kenley. “Safety and metabolism of AOD9604, a novel nutraceutical ingredient for improved metabolic health.” Journal of Endocrinology and Metabolism 4.3 (2014): 64-77.
5. Valentino, M A et al. “Central and peripheral molecular targets for antiobesity pharmacotherapy.” Clinical pharmacology and therapeutics vol. 87,6 (2010): 652-62. doi: 10.1038/clpt.2010.57
6. Ma GY, Macaulay SL, Maggs JA, Armstrong JM, Bornstein J. The mechanism of the hyperglycaemic action of synthetic peptides related to the C-terminal sequence of human growth hormone. Biochim Biophys Acta. 1982 Jun 16;716(3):400-9. doi: 10.1016/0304-4165(82)90033-2. PMID: 6810951. https://pubmed.ncbi.nlm.nih.gov/6810951/
7. Kwon DR, Park GY. Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model. Ann Clin Lab Sci. 2015 Summer;45(4):426-32. PMID: 26275694. https://pubmed.ncbi.nlm.nih.gov/26275694/
8. Image source: National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 146681838, CID 146681838 https://pubchem.ncbi.nlm.nih.gov/compound/146681838.