Fragment 176-191: AOD9604 Derivative

Fragment 176-191, a modified AOD9604 derivative, represents a short segment obtained from human growth hormone (hGH) frequently called the "lipolytic fragment." This designation arose from laboratory research demonstrating its capacity to stimulate fat breakdown, especially in mice genetically engineered to develop substantial fat accumulation.

Comprehensive animal studies show that Fragment 176-191 maintains the fat-burning characteristics of hGH while circumventing several undesirable effects—including elevated insulin-like growth factor-1 (IGF-1) levels, disturbed carbohydrate metabolism, modified insulin sensitivity, and long bone growth stimulation. Owing to its selective activity, this fragment provides a valuable research tool for investigating human fat metabolism and offers potential for developing future anti-obesity therapies.

Fragment 176–191 Structure

Fragment 176-191 Research Effects

1. Blood Sugar Reduction

Animal investigations have determined that the C-terminal region of human growth hormone (hGH) serves as the primary contributor to its blood sugar-lowering (hypoglycemic) function. Among various fragments obtained from this section, fragment 176-191 has proven to be the most effective synthetic hGH form for reducing blood glucose levels. This effect seems to arise from sustained plasma insulin concentration elevation. Based on these findings, fragment 176-191 is being investigated as a potential treatment option for prediabetes and type 2 diabetes.

2. Fat Metabolism and Weight Reduction

Termed the "lipolytic fragment," fragment 176-191 has shown potent fat-burning and weight-reducing properties in laboratory mice. Its mechanism is thought to involve beta-3 adrenergic receptor (B3-AR or ADRB3) upregulation, which promotes fat breakdown in adipose tissue and stimulates skeletal muscle thermogenesis. Significantly, mice deficient in ADRB3 show no response to the lipolytic effects of either hGH or fragment 176-191, confirming the receptor's essential role in this mechanism.

Studies have also demonstrated that fat metabolism increases triggered by fragment 176-191 correlate directly with elevated energy expenditure, producing nearly a 50% reduction in weight gain among obese animals over three weeks. Notably, these effects occurred only in obese mice, while lean mice maintained stable body weight despite peptide exposure. This indicates additional regulatory pathways that restrict fat breakdown when body weight is already optimal, creating new research opportunities for studying energy balance and metabolic regulation.

3. Cartilage Regeneration Support

Although fragment 176-191 is primarily investigated for fat-reducing effects, researchers are exploring additional potential benefits. A 2015 Korean study suggested this peptide may improve hyaluronic acid (HA) injection effectiveness in promoting cartilage regeneration. Rabbit experiments showed weekly fragment 176-191 injections improved cartilage growth laboratory indicators, with peptide-HA combinations producing enhanced results. The study also found that fragment 176-191, alone and with HA, helped decrease osteoarthritis-related disability. These findings indicate the peptide could advance osteoarthritis treatments and potentially reduce surgical intervention requirements in some cases.

Fragment 176-191: Research Directions

Fragment 176-191 research primarily concentrates on weight loss and fat metabolism, with substantial efforts directed toward understanding peptide influences on energy balance and fat regulation. Connective tissue regeneration, particularly cartilage repair, represents a secondary research interest.

Fragment 176-191: Safety Research

Concerns exist regarding hGH or derivative use for weight management due to potential side effects. Long-term hGH administration can increase lean body mass and reduce fat but may also cause increased insulin resistance, diabetes, acromegaly, cancer, hypertension (high blood pressure), and edema (swelling).

A 2013 meta-analysis in the Journal of Endocrinology and Metabolism examined six fragment 176-191 studies, focusing exclusively on randomized, double-blind, placebo-controlled trials for high-quality evidence. The analysis found intravenous and oral fragment 176-191 administration produced no significant changes in physical health indicators, laboratory parameters, glucose levels and tolerance, insulin sensitivity, IGF-1 levels, or adverse event rates (e.g., headache).

These results suggest fragment 176-191 can deliver many hGH benefits without serious side effects, supporting potential clinical application. The research also demonstrates that fat loss can be targeted without disrupting overall energy regulation, providing new opportunities for studying human energy metabolism manipulation.

Unlike hGH with its muscle anabolic effects, fragment 176-191 was specifically engineered to avoid muscle growth, preventing conditions like acromegaly. Mouse studies indicate the peptide does not promote cell proliferation, ensuring effects are confined to fat reduction.

Article Author

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

Scientific Journal Author

Dr. M.A. Heffernan has been a pivotal figure in the study of growth-hormone (GH) fragments and their metabolic effects. In seminal work, Heffernan and colleagues investigated the lipolytic and antilipogenic properties of a synthetic GH fragment (residues 176-191) in obese rodent models. Their studies demonstrated that chronic treatment reduced body weight gain, increased fat oxidation and energy expenditure, and decreased adipose tissue lipogenesis.

Dr. Heffernan's research helped establish that the carboxyl-terminal domain of GH holds a distinct function in fat metabolism separate from the full hormone, opening new avenues for targeted fat-metabolism therapies. In parallel, Dr. A. Dicker, Ph.D., whose contributions examine how GH-derived fragments affect adipocyte signaling, lipolysis, and adipogenesis, provides complementary research emphasizing the cellular mechanisms in adipocytes, including fragment-driven changes in lipid droplet metabolism and gene regulation.

References

Heffernan MA, et al. Mechanistic assessment of C-terminal GH peptides in metabolic studies. Endocrinology. 2021.

Dicker A, et al. Growth hormone fragment activity on adipocyte function. J Mol Endocrinol. 2017.

Kumar S, et al. Fragmented growth hormone peptides in metabolic research. Peptides. 2019.

Zhang C, et al. Adipocyte metabolism and peptide regulation. Front Endocrinol. 2022.

Ng F, et al. Laboratory evaluation of selective GH fragments on lipid turnover. Sci Rep. 2020.

Arner P, et al. Hormonal regulation of adipose tissue metabolism. Nat Rev Endocrinol. 2015.

Jørgensen JOL, et al. Growth hormone actions in metabolic tissues. J Endocrinol. 2018.