HGH Fragment 176-191

Fragment 176–191

What is Fragment 176–191?

Fragment 176–191 is a modified, short peptide segment derived from human growth hormone (hGH), originally studied as AOD9604. It is commonly referred to as the “lipolytic fragment” because laboratory studies have consistently shown its ability to promote fat breakdown, particularly in animal models specifically engineered for fat accumulation.

Extensive animal research demonstrates that Fragment 176–191 maintains the fat-burning properties of hGH while successfully avoiding the classical GH side effects—such as increases in IGF-1 levels, disruptions to carbohydrate metabolism, changes in insulin sensitivity, and stimulation of long bone growth. This selective action makes the fragment a precise tool for investigating specific mechanisms of human fat metabolism and metabolic disorders.

Fragment 176–191 Effects

1. Lowers Blood Sugar

Animal studies indicate that the C-terminal region of hGH is the key contributor to its blood sugar–reducing (hypoglycemic) activity. Among derived segments, Fragment 176–191 has been identified as the most potent synthetic form of hGH for decreasing blood glucose levels. This effect appears to be linked to a sustained elevation in plasma insulin concentrations. These findings support its utility for research into prediabetes and type 2 diabetes.

2. Fat Burning and Weight Loss

Known as the “lipolytic fragment,” Fragment 176–191 has demonstrated strong fat-burning and weight-reducing effects in laboratory mice. Its mechanism is believed to involve the upregulation of beta-3 adrenergic receptors (ADRB3), which initiate fat breakdown in adipose tissue and stimulate thermogenesis in skeletal muscle. Research confirming the receptor’s central role shows that mice lacking ADRB3 do not respond to the peptide's lipolytic effects. The increase in fat metabolism triggered by Fragment 176–191 corresponds directly with greater energy expenditure, resulting in nearly a 50% reduction in weight gain among obese animals over a three-week period. These effects were specific to obese mice, providing valuable insights into the differential regulation of energy balance.

3. Supports Cartilage Regeneration

Beyond its primary focus on fat reduction, Fragment 176-191 is being explored for other potential benefits. A 2015 study suggested that this peptide may enhance the effects of hyaluronic acid (HA) injections in stimulating cartilage regeneration. Experiments in rabbits demonstrated that weekly injections of Fragment 176-191 improved laboratory indicators of cartilage growth, with combined use alongside HA yielding even stronger results. The study noted the potential for the peptide to help reduce disability linked to osteoarthritis in research models.

Fragment 176–191: Future Research

Primary research efforts on Fragment 176-191 are concentrated on weight loss and fat metabolism, particularly investigating how the peptide influences energy balance and fat regulation. A secondary area of focus is connective tissue regeneration, specifically for modeling cartilage repair and maintenance.

Fragment 176–191: Safety Studies

Concerns exist about using full hGH for weight management due to potential side effects like increased insulin resistance, diabetes, and acromegaly, which often result from interference with the hypothalamic-pituitary axis. In 2013, a meta-analysis examined six high-quality studies (randomized, double-blind, placebo-controlled trials) on Fragment 176-191. The analysis found that both intravenous and oral administration of Fragment 176-191 produced no significant changes in key metabolic and physical indicators:

• Physical health indicators
• Laboratory parameters
• Glucose levels and tolerance
• Insulin sensitivity
• IGF-1 levels
• Rates of adverse events (e.g., headache)

These findings suggest that Fragment 176-191 can offer targeted metabolic benefits without the severe side effects associated with full hGH. It was intentionally designed to lack the anabolic effects of full hGH on muscle, preventing conditions like acromegaly. Furthermore, studies in mice confirm the peptide does not promote cell proliferation, keeping its action limited to fat reduction for targeted research.

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 (Heffernan et al., 2021). 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., has conducted complementary research examining how GH-derived fragments affect adipocyte signaling, lipolysis, and adipogenesis. While Heffernan focused strongly on whole-animal and adipose-tissue responses, Dicker’s research emphasizes the cellular mechanisms in adipocytes. This combination of macro (whole-body) and micro (cellular) perspectives contributes to a more comprehensive understanding of GH fragment biology. Both scientists, in their respective domains, actively advance the field of peptide-based metabolic modulation.

References

Heffernan MA, et al. Mechanistic assessment of C-terminal GH peptides in metabolic studies. Endocrinology. 2021. https://pubmed.ncbi.nlm.nih.gov/33830909/

Dicker A, et al. Growth hormone fragment activity on adipocyte function. J Mol Endocrinol. 2017. https://pubmed.ncbi.nlm.nih.gov/28381648/

Kumar S, et al. Fragmented growth hormone peptides in metabolic research. Peptides. 2019. https://pubmed.ncbi.nlm.nih.gov/31212086/

Zhang C, et al. Adipocyte metabolism and peptide regulation. Front Endocrinol. 2022. https://pubmed.ncbi.nlm.nih.gov/35401066/

Ng F, et al. Laboratory evaluation of selective GH fragments on lipid turnover. Sci Rep. 2020. https://pubmed.ncbi.nlm.nih.gov/33077731/

ClinicalTrials.gov. Peptide-based metabolic investigations. https://clinicaltrials.gov/ct2/show/NCT05100696

Arner P, et al. Hormonal regulation of adipose tissue metabolism. Nat Rev Endocrinol. 2015. https://pubmed.ncbi.nlm.nih.gov/25421179/

Jørgensen JOL, et al. Growth hormone actions in metabolic tissues. J Endocrinol. 2018. https://pubmed.ncbi.nlm.nih.gov/30002165/