HGH Fragment 176-191

also known as: HGH Frag 176-191, AOD-9401 (related), Lipolytic fragment of GH, Frag 176-191

The lipolytic fragment that inspired AOD-9604 — binds a hypothesized non-GHR receptor to drive fat oxidation without growth-promoting effects, though human efficacy data are weak.

A synthetic 16-residue peptide reproducing the C-terminal fragment of human growth hormone (residues 176–191), the region proposed by Ng and Bornstein in the 1980s to mediate GH's lipolytic effects independently of its growth-promoting effects, and the direct predecessor to Metabolic Pharmaceuticals' AOD-9604.

Mechanism of action

Proposed to act through a non-GH-receptor mechanism to stimulate lipolysis and fat oxidation in adipose tissue. Unlike full-length GH, the 176–191 fragment does not stimulate IGF-1 production, does not cause the insulin resistance associated with GH excess, and does not produce growth effects in GH-deficient animal models. The specific receptor mediating these fat-burning effects has never been definitively identified, and the mechanism remains partly hypothetical.

Primary uses

Fat-loss research (preclinical)
Community bodybuilding / body-recomposition use (unapproved, weak human efficacy)

Typical dosing

250–500 µg daily or twice daily (subcutaneous)

Community dosing; no clinical validation. AOD-9604 (the analog) failed to show statistically significant weight loss vs placebo at 1 mg/day in a 12-week Phase 2b trial in 534 obese adults.

Regulatory status

Not approved for any indication. AOD-9604 (a tyrosine-modified analog of this fragment) was developed by Metabolic Pharmaceuticals for obesity but failed Phase 2b efficacy in 2007. The unmodified Frag 176-191 has no clinical development program and is sold purely as a research chemical.

References

[pubmed] Ng FM, Bornstein J. "Hyperglycemic action of synthetic C-terminal fragments of human growth hormone." Am J Physiol, 1978;234:E521-526.
[pubmed] Heffernan M, et al. "The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice." Endocrinology, 2001;142:5182-5189.
[news-release] Metabolic Pharmaceuticals. "AOD9604 Phase 2b obesity trial results." 2007. (Trial failed primary efficacy endpoint.)

Related peptides

AOD-9604

A short GH fragment marketed heavily as a "fat-loss peptide" — but with a clinical record that has not supported meaningful weight loss in humans.

Somatropin (HGH)

FDA-approved recombinant human growth hormone — the direct hormone replacement, with multiple clinical indications, prescription-only status, and specific federal criminal provisions against off-label distribution.

Adipotide

A preclinical concept that killed white adipose tissue by inducing vasculature apoptosis in obese rhesus monkeys — dramatic weight loss, but also nephrotoxicity that stopped it from advancing to humans.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.