hGH Fragment 176-191

The Fat Loss Specialist

Achieve Leaner Body with hGH Fragment 176-191

hGH Fragment 176-191 is a small, specific portion of the larger human growth hormone molecule. This fragment, composed of amino acids 176 to 191, is considered the “lipolytic fragment” because it has been found to specifically target and promote the breakdown of fat. Its primary researched benefit is its ability to reduce adipose tissue, which is essentially body fat, more effectively than its larger counterpart while avoiding some of the regulatory effects on blood sugar and growth that the full hormone might induce. This peptide has attracted interest not only for its potential in obesity treatment but also in the study of how specific hormone segments influence various bodily functions.

Potential Benefits Under Research

• Enhanced Fat Loss: It specifically targets fat cells and enhances the breakdown of fat, making it a promising candidate for obesity treatment and weight management.
• Does Not Affect Blood Sugar Levels: Unlike the full human growth hormone, this fragment does not seem to impact insulin levels, making it a safer alternative for managing body composition without affecting blood sugar balance.
• Muscle Mass Preservation: Early studies suggest that while it helps reduce fat, it does not negatively impact muscle mass, making it attractive for body composition improvement.

Dosing Protocol for Research Purposes

• 200 to 600 mcg per day, split into two or three administrations.

Overview

Fragment 176-191 (modified version of AOD9604) is a small piece of human growth hormone (hGH) that is sometimes referred to as the “lipolytic fragment.” Fragment 176-191 earned this latter name due to the fact that laboratory research has shown it to enhance fat burning, particularly in mice genetically engineered to produce large fat stores. Fragment 176-191 has been heavily researched in animal models because even while it preserves the fat ­burning effects of hGH, it avoids some other effects of its parent protein such as increasing insulin-like growth factor-1 (IGF-1) levels, negatively impacting carbohydrate metabolism, altering insulin sensitivity, increasing long bone growth, and so forth. The targeted effects of fragment 176-191 make it useful for exploring human fat metabolism and may eventually provide the basis for developing anti­-obesity medications. 

Structure

Source: PubChem
Sequence: Tyr-Leu-Arg-lle-Val-Gln-Cys-Arg-Ser­Val-Glu-Gly-Ser-Cys-Gly-Phe
Molecular Formula: C78H125N23O23S2 Molecular Weight: 1817.12 g/mol
CAS Number: 66004-57-7

Fragment 176-191 Effects 

1. Lowers Blood Sugar

Research in animals has revealed that the c­terminal end of hGH is primarily responsible for the protein’s hypoglycemic (lowering blood sugar) effects. Testing of at least six different fragments derived from this section of hGH has shown that fragment 176-191 is the most effective synthetic derivative of hGH for lowering blood sugar levels. This effect is secondary to a sustained increase in plasma insulin levels. There is some interest in using fragment 176-191 as a treatment for both prediabetes and type 2 diabetes. 

2. Fat Burning And Weight Loss

Fragment 176-191 has earned the nickname of “lipolytic fragment” because testing in mice has revealed the peptide to have substantial fat-burning and weight-loss properties. It is thought that this action is mediated through an increase in the production of beta-3 adrenergic receptors (B3-AR or ADRB3). Agonist action at ADRB3 is known to directly increase fat burning in adipose tissue and is also responsible for thermogenesis in skeletal muscle. Mice that have been genetically modified to produce no ADRB3 do not respond to the lipolytic effects of hGH or fragment 176-191. 

Studies show that the increased fat burning associated with fragment 176-191 directly correlates with energy expenditure and thus weight reduction, leading to a nearly 50% reduction in weight gain in obese animals over a three-week course. Interestingly, the weight loss effects were seen only in obese mice, with lean mice maintaining normal body weight, on average, even when exposed to fragment 176-191. These findings indicate that there are secondary regulatory pathways for lipolysis that override ADRB3 function when body weight is at or near ideal, opening up areas for additional research into energy homeostasis.

Body weight in genetically obese mice after two weeks of treatment with a single daily dose of fragment 176-191
Source: Oxford Academic

Effect of saline (control), fragment 176-191, and hGH on white adipose tissue mass in obese mice over 14 days
Source: Oxford Academic

3. Promotes Cartilage Regeneration

Though fragment 176-191 is primarily of interest for its lipolytic properties, the peptide is under investigation for other possible benefits. Of note, a 2015 article out of Korea revealed that fragment 176-191 may be able to potentiate the effects of
hyaluronic acid injections in promoting cartilage regeneration. Studies in rabbits indicated that weekly injections of fragment 176-191 increase laboratory measures of cartilage growth and that co­ administration of the peptide with hyaluronic acid
(HA) produces even more substantial effects. Similarly, the study found that fragment 176-191, both alone and in combination with HA, reduce disability associated with osteoarthritis. There is hope that this may lead to advanced therapies for osteoarthritis and may even eliminate the need for surgery in certain settings.

Fragment 176-191 Safety Studies

There is some concern that the use of hGH or its derivatives for weight control may have unwanted side effects. This concern arises from the fact that studies of hGH have shown that long-term exogenous administration while increasing lean body mass and decreasing adipose tissue, can also cause: 

• increased insulin resistance,
  • diabetes,
  • acromegaly,
  • cancer,
  • hypertension (high blood pressure), and
  • edema (swelling).

In 2013, a study published in the Journal of Endocrinology and Metabolism evaluated six studies of fragment 176-191 to assess the rate and significance of negative effects associated with the peptide. The study, included only research that followed the randomized, double-blinded, placebo-­controlled model of a phase llb clinical trial in order to keep the highest possible standards of evidence. It found that IV and oral administration of Fragment 176-191, when compared to placebo, led to no changes in: 

• physical findings,
  • laboratory parameters,
  • glucose levels,
  • glucose tolerance,
  • insulin sensitivity,
  • IGF-1 levels, or
  • rates of adverse events (e.g. headache)

The results of this meta-analysis suggest that fragment 176-191 offers many of the benefits of hGH without the associated negative (and often serious) side effects. These findings further the for pursuing regulatory approval for the use of fragment 176-191 in the clinical setting but also offer insight into the regulation of human growth, fat deposition, and energy homeostasis. These findings make it clear that it is possible to target fat loss without affecting energy homeostasis in other nutrient pathways, opening the door for a deeper exploration of human energy regulation and methods of manipulating it.

 It is worth noting that while hGH has anabolic effects on muscle, fragment 176-191 was specifically selected for its ability to avoid anabolism entirely. This is critical to ensuring that the peptide has targeted lipolytic effects and does not produce acromegaly or any of the other conditions associated with hGH administration. Studies in mice reveal that fragment 176-191 do not increase cell proliferation. 

Fragment 176-191 Future Research

The primary area of research for fragment 176-191 is in weight loss and lipolysis where significant effort is being expended to learn how the peptide can be used to understand fat metabolism and energy homeostasis. The most active secondary area of research is in connective tissue regeneration, particularly cartilage repair. 

Article Author

The above literature was researched, edited and organized by Dr. Logan, M.D. Dr. Logan holds a doctorate degree from Case Western Reserve University School of Medicine and a B.S. in molecular biology. 

Scientific Journal Article 

Frank NG, M.D. is one of the leading scientists discovering how both AOD9604 and Fragment 176- 191 function. He extensively studied their effects on lipid metabolism in obese mice, fat oxidation, weight loss, oral digestion, glucose transport, and hyperglycemia. He has over 64 publications and studies at the Department of Biochemistry and Molecular Biology — Monash University, Australia. 

Frank NG, M.D. is being referenced as one of the leading scientists involved in the research and development of Fragment 176-191. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Guide to Peptide and this doctor. The purpose of citing the doctor is to acknowledge, recognize, and credit the exhaustive research and development efforts conducted by the scientists studying this peptide. Frank NG, M.D. is listed in [1] [2] and [4] under the referenced citations. 

Referenced Citations 

1. F. M. Ng and J. Bornstein, “Hyperglycemic action of synthetic C-terminal fragments of human growth hormone,” Am. J. Physiol., vol. 234, no. 5, pp. E521-526, May 1978. 
2. M. Heffernan et al., “The Effects of Human GH and Its Lipolytic Fragment {AOD9604) on Lipid Metabolism Following Chronic Treatment in Obese Mice and? 3-AR Knock­out Mice,” Endocrinology, vol. 142, no. 12, pp. 5182-5189, Dec. 2001. 
3. R. Ferrer-Lorente, C. Cabot, J.-A. Fernandez- L6pez, and M. Alemany, “Combined effects of oleoyl-estrone and a beta3-adrenergic .agonist (CL316,243) on lipid stores of diet­ induced overweight male Wistar rats,” Life Sci., vol. 77, no. 16, QR- 2051-2058, SeR.:, 2005. 
4. F. M. Ng, J. Sun, L. Sharma, R. Libinaka, W. J. Jiang, and R. Gianello. “Metabolic studies of a Synthetic lipolytic domain (AOD9604)_Qf human growth hormone,” Harm. Res., vol. 53, no. 61 RR-274-278, 2000. 
5. H. Stier, E. Vos, and D. Kenley, “Safety and Tolerability. of the Hexadecapeptide AOD9604 in Humans,” J. Endocrinol. Metab., vol. 3, no. 1-2, RR-7-15-15, Apr. 2013.
6. M. A. Heffernan et al., “Increase of fat oxidation and weight loss in obese mice caused by. chronic treatment with human growth hormone or a modified C-terminal fragment,” Int. J. Obes. Relat. Metab. Disord. J. Int. Assoc. Study. Obes .• vol. 25, no. 10, pp. 1442-1449, Oct. 2001.
7. 7. D.R. Kwon and G. Y. Park, “Effect of Intra­-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model,” Ann. Clin. Lab. Sci., vol. 45, no. 4, RR.:. 426-432, Jul. 2015.