- Sequence: hGH amino acids 176–191 (C-terminal tail)
- Molecular weight: 1817.12 Da
- CAS: 221231-10-3
- Also known as: AOD-9604, hGH Frag 176-191
- Primary action: Selective lipolysis via β3-adrenergic and lipase activation
- IGF-1 effect: None (does not bind GH receptor in an IGF-1-stimulating manner)
01 What Is Fragment 176-191?
Fragment 176-191 is a synthetic peptide corresponding to amino acids 176 through 191 of the human growth hormone (hGH) sequence — specifically the C-terminal alpha-helical region of hGH. This region was identified through truncation studies as the portion of the hGH molecule responsible for its lipolytic (fat-mobilising) activity.
Full hGH has a complex pharmacological profile: it stimulates IGF-1 secretion (anabolic), promotes muscle growth, can induce insulin resistance at supraphysiological doses, and simultaneously promotes fat oxidation. Researchers at Metabolic Pharmaceuticals sought to isolate the fat-burning activity in a compound without the anabolic or anti-insulin side effects — resulting in Fragment 176-191 and its stabilised analogue, AOD-9604.
02 Fragment 176-191 vs Full HGH
Understanding Fragment 176-191 requires understanding what it removes from the full hGH molecule:
| Effect | Full hGH | Fragment 176-191 |
|---|---|---|
| IGF-1 stimulation | Yes (major) | No |
| Muscle growth (anabolic) | Yes | No |
| Lipolysis (fat burning) | Yes | Yes (preserved) |
| Insulin resistance | Yes (high dose) | No |
| Bone growth | Yes | No |
| Blood glucose effect | Raises (anti-insulin) | Neutral |
| Molecular weight | ~22,000 Da | 1,817 Da |
This profile makes Fragment 176-191 a uniquely selective metabolic research tool — preserving the fat oxidation activity of hGH while removing the broad endocrine effects that complicate interpretation of hGH studies and limit therapeutic applications.
03 Lipolytic Mechanism
The mechanism by which Fragment 176-191 promotes lipolysis has been investigated across several in vitro and in vivo studies:
Beta-3 Adrenergic Activity
Fragment 176-191 appears to stimulate lipolysis partly through β3-adrenergic receptor activation in adipose tissue. β3-AR activation triggers intracellular cAMP signalling cascades that activate hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) — the two enzymes responsible for breaking down stored triglycerides into free fatty acids and glycerol for oxidation.
Anti-Lipogenic Effect
Beyond promoting fat breakdown, preclinical data suggest Fragment 176-191 also inhibits lipogenesis — the formation of new fat from dietary carbohydrates. Rodent studies using high-fat diet models showed that Fragment 176-191-treated animals had both lower fat mass accumulation and higher baseline lipolytic rates compared to controls.
No GH Receptor Binding (Type II)
Full hGH binds GH receptor (GHR) dimers to stimulate IGF-1 secretion via JAK2/STAT5b signalling. Fragment 176-191 does not bind GHR in this manner — it lacks the receptor-binding domains present in the N-terminal portion of hGH. This mechanistic separation is the basis for its clean metabolic profile.
04 Clinical Data — AOD-9604
The most clinically advanced data for this compound family comes from Metabolic Pharmaceuticals' AOD-9604 programme, which included Phase I and Phase II human trials:
- Design: Randomised, double-blind, placebo-controlled, 12-week
- Population: Obese adults (BMI 35–40)
- Dose: 1 mg/day oral AOD-9604
- Primary endpoint: Body weight change
- Result: Statistically significant weight loss vs placebo (~2.5 kg at 12 weeks)
- Safety: No significant adverse effects; no change in glucose/IGF-1
- Status: Phase III not initiated (modest effect size)
A 1 mg/day oral dose produced modest but measurable weight loss in the Phase II study. Higher doses (2.5 mg/day) did not produce significantly greater weight loss — suggesting a plateau in the dose-response curve at oral delivery. Subcutaneous delivery routes, which avoid first-pass hepatic degradation, may produce different pharmacokinetics.
05 Fragment 176-191 vs AOD-9604
The two terms are frequently used interchangeably but there is a structural distinction:
- Fragment 176-191 — the native hGH sequence, amino acids 176–191 as they appear in natural growth hormone
- AOD-9604 — the same sequence with a modified N-terminal tyrosine residue that stabilises the peptide against degradation and improves bioavailability
Both share CAS 221231-10-3 in most databases and are considered pharmacologically equivalent in the research literature. The stabilised modification in AOD-9604 confers improved half-life, which was critical for the oral Phase II trial formulation.
06 Comparison: Fat Loss Peptides
| Peptide | Mechanism | IGF-1 Effect | Clinical Stage |
|---|---|---|---|
| Fragment 176-191 | β3-AR, HSL, anti-lipogenic | None | Phase II (completed) |
| AOD-9604 | Same as above (stabilised) | None | Phase II (completed) |
| Adipotide (CKGGRAKDC) | Vascular targeted apoptosis in fat | None | Phase I (primate) |
| Full hGH | GHR → IGF-1 + lipolysis | Major stimulation | Approved (GH deficiency) |
| Retatrutide | GLP-1/GIP/glucagon triple agonist | None directly | Phase III ongoing |
07 Protocol Notes
In rodent preclinical studies, Fragment 176-191 has been administered subcutaneously at doses of 500 mcg/kg once or twice daily. The Phase II human trial used 1 mg/day oral AOD-9604. Subcutaneous routes are expected to have superior bioavailability to oral administration for this peptide class.
The peptide should be stored lyophilised at −20°C and reconstituted with bacteriostatic water immediately before use. Reconstituted solutions should be stored at 4°C and used within 4–6 weeks.
08 Frequently Asked Questions
What is Fragment 176-191?
The C-terminal lipolytic sequence of human growth hormone (aa 176–191), isolated as a standalone peptide that retains hGH's fat-burning activity without its IGF-1-stimulating or insulin-resistance effects.
How does it differ from full HGH?
It lacks the receptor-binding domain that triggers IGF-1 secretion and anabolic effects. It retains only the lipolytic tail sequence, making it a selective metabolic research compound.
Does Fragment 176-191 work for fat loss?
Rodent studies showed significant lipolytic effects. A Phase II human trial with AOD-9604 showed modest (~2.5 kg over 12 weeks) but statistically significant weight loss vs placebo at 1 mg/day oral dosing.
What is the difference between Fragment 176-191 and AOD-9604?
AOD-9604 is a stabilised analogue with a modified N-terminal tyrosine for improved bioavailability. They share CAS 221231-10-3 and are pharmacologically equivalent in most research contexts.
Is Fragment 176-191 safe?
Phase I/II data showed no significant adverse effects on glucose, IGF-1, or insulin sensitivity. Long-term human safety data is limited. For research use only.