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FRAGMENT 176-191 PEPTIDE

SKU 00634
$39.99
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Fragment 176-191

The fragment 176-191 has profound lipolytic action (ie. fat burning), which results in decreased fat mass, increased lean mass, and lasting weight loss in adults [1]–[3]. Studies done both in vitro and in vivo have indicated that this response is mediated in part by an increase in β3-adrenoceptor response [4], increased activity of hormone-sensitive lipase which breaks down fat [5], and an inhibitory effect on the hormone insulin which instructs fat cells to take in sugar and convert it to fat [6].

To synthesize a fragment that contains only the lipolytic domain that is responsible for the fat burning action, scientists started with a shorter version, AOD9401, that was already known to induce lipolysis and inhibit fat storing. In humans, AOD9401 also induces weight loss without affecting food intake as well as increasing lipolytic sensitivity and increasing fat oxidation with no adverse effects on insulin sensitivity [7], [8]. Thus, researchers wanted to improve upon this parent compound which is what led to Frag 176-191.

Primarily, the weight loss attributes of Frag 176-191 can be attributed to its binding to β3-adrenergic receptors…

What are β3-adrenergic receptors?

To understand the fat burning capacity of Frag 176-191, you first need to understand some of the molecular biology of fat burning itself. Frag 176-191 activates β3-adrenergic receptors, which are proteins that serve to transmit signals from outside of cells in order to change energy metabolism inside of cells. The main actions of β3-adrenergic receptors are the following:

  1. Enhancement of lipolysis in adipose tissue (ie. fat burning in fat tissue) [9]
  2. Thermogenesis in skeletal muscle (ie. heat production via energy metabolism) [10]
  3. Raising basal metabolic rate (BMR) [11]

Beta adrenergic receptors are the target of adrenaline, meaning that some of the actions of Frag 176-191 and adrenaline are similar, although Frag 176-191 does not elicit a “fight or flight” response or raise cortisol like adrenaline does [12].

Why not just take full length?

Unfortunately, there are unwanted side effects of full-length that limit its therapeutic value: glucose intolerance and insulin resistance are the most common, and this limits long term use. In contrast, glucose control was monitored in individuals taking Frag 176-191, and OGTT glucose testing was conducted on all patients at various time points during clinical study periods.

No significant changes or trends in glucose levels in any Frag 176-191 treatment groups have been observed, demonstrating that Frag 176-191 does not deteriorate glucose control or induce insulin resistance. As a matter of fact, treatment with Frag 176-191 actually showed a positive effect in subjects who had pre-existing impaired glucose tolerance. In a 12 weeks treatment study, patients with impaired glucose tolerance who took taking Frag 176-191 were less likely to develop diabetes during the study than subjects taking placebo [12].

Full length also activates the IGF-1 axis which is responsible for the growth promoting effects. In a recent clinical trial of effects in adults, full length caused an increase in IGF-1 levels over a 6-month dosing period and unfortunately decreased glucose tolerance in participants. Increased IGF-1 may have a variety of undesirable effects, including an increase in risk or prostate cancer and breast cancer [13], [14].

Obviously, this risk negates much of the enthusiasm for full length. Fortunately, in all the clinical studies of Frag 176-191 completed as of yet, IGF-1 levels were monitored long-term, and there were no clinically significant differences between dose groups or placebo. Thus, there is no concern of increased IGF-1 levels when using Frag 176-191.



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Why did some clinical studies of Frag 176-191 fail to reduce body fat?

The problem with the underwhelming clinical results of Frag 176-191 is obviously due to oral delivery, which researchers chose to use rather than subcutaneous injection or nasal spray delivery (which bypasses proteolytic degradation in the stomach and GI tract). The reason why researchers chose to study oral delivery is simply because there is a much larger potential market for oral products. Thus, the negative results from the Frag 176-191 pill studies should not be used to disparage the injectable or nasal spray formulations.

Furthermore, some clinical trials have actually used a fragment which is equivalent to Frag 177-191. However, our product has an additional amino acid at the N-terminus, yielding Frag 176-191. This small different is crucial to the overall stability of the peptide, which is necessary for sufficient half-life in systemic circulation.

Future Research Directions

Currently, Frag 176-191 is the subject of a clinical study examining the effectiveness aimed at reducing cellulite and subcutaneous fat (as opposed to visceral fat which was the goal of all previous clinical trials) [15].

This information is for educational purposes only. THE PRODUCTS DESCRIBED HEREIN ARE FOR RESEARCH USE ONLY. All clinical research must be conducted with oversight from the appropriate Institutional Review Board (IRB). All preclinical research must be conducted with oversight from the appropriate Institutional Animal Care and Use Committee (IACUC) following the guidelines of the Animal Welfare Act (AWA)

References

  1. C. H. Gravholt, O. Schmitz, L. Simonsen, J. Bülow, J. S. Christiansen, and N. MØller, “Effects of a physiological GH pulse on interstitial glycerol in abdominal and femoral adipose tissue,” Am. J. Physiol. - Endocrinol. Metab., 1999.
  2. J. Rodríguez-Arnao, A. Jabbar, K. Fulcher, G. M. Besser, and R. J. M. Ross, “Effects of growth hormone replacement on physical performance and body composition in GH deficient adults,” Clin. Endocrinol. (Oxf)., 1999.
  3. G. A. Aguirre, J. R. Ita, R. G. Garza, and I. Castilla-Cortazar, “Insulin-like growth factor-1 deficiency and metabolic syndrome,” J. Transl. Med., 2016.
  4. M. Beauville et al., “Effect of long-term administration in GH-deficient adults on fat cell epinephrine response,” Am. J. Physiol. - Endocrinol. Metab., 1992.
  5. J. Dietz and J. Schwartz, “Growth hormone alters lipolysis and hormone-sensitive lipase activity in 3T3-F442A adipocytes,” Metabolism, 1991.
  6. M. Ridderstråle and H. Tornqvist, “Effects of tyrosine kinase inhibitors on tyrosine phosphorylations and the insulin-like effects in response to human growth hormone in isolated rat adipocytes,” Endocrinology, 1996.
  7. M. A. Heffernan, W. J. Jiang, A. W. Thorburn, and F. M. Ng, “Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism,” Am. J. Physiol. - Endocrinol. Metab., 2000.
  8. F. M. Ng, J. Sun, L. Sharma, R. Libinaka, W. J. Jiang, and R. Gianello, “Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone,” Horm. Res., 2000.
  9. R. Ferrer-Lorente, C. Cabot, J. A. Fernández-López, and M. Alemany, “Combined effects of oleoyl-estrone and a β3-adrenergic agonist (CL316,243) on lipid stores of diet-induced overweight male Wistar rats,” Life Sci., 2005.
  10. L. Poekes, N. Lanthier, and I. A. Leclercq, “Brown adipose tissue: A potential target in the fight against obesity and the metabolic syndrome,” Clinical Science. 2015.
  11. A. M. Cypess et al., “Activation of human brown adipose tissue by a β3-adrenergic receptor agonist,” Cell Metab., 2015.
  12. Stier, “Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans,” J. Endocrinol. Metab., 2013.
  13. J. M. Chan et al., “Plasma insulin-like growth factor-I and prostate cancer risk: A prospective study,” Science (80-. )., 1998.
  14. S. E. Hankinson et al., “Circulating concentrations of insulin-like growth factor-I and risk of breast cancer,” Lancet, 1998.
  15. M. A. Valentino, J. E. Lin, and S. A. Waldman, “Central and peripheral molecular targets for antiobesity pharmacotherapy,” Clinical Pharmacology and Therapeutics. 2010.

*The information herein is for educational and informational purposes only. THIS PRODUCT IS FOR RESEARCH USE ONLY. For use in animal studies, all research must be conducted with oversight from the appropriate Institutional Animal Care and Use Committee (IACUC) following the guidelines of the Animal Welfare Act (AWA).

Storage: Lyophilized peptide should be stored at -20°C (freezer), and the reconstituted peptide solution at 4°C (refrigerated). Use within 24 months. Once reconstituted use within 30 days. Do not freeze once reconstituted.


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