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FAT LOSSResearch OnlyFAT LOSSLIPOLYSISHGH FRAGMENT

AOD-9604

Also known as: Anti-Obesity Drug 9604 · hGH Fragment 177-191 · Tyr-hGH Frag 177-191

21.3k views/week 184 citations 18 edits Updated 4/6/2026

AOD-9604 is a modified fragment of human growth hormone (hGH residues 177–191) with an added N-terminal tyrosine residue. Unlike full HGH, it stimulates lipolysis and inhibits lipogenesis without affecting growth, IGF-1 levels, insulin sensitivity, or blood glucose — making it a targeted fat-loss agent. FDA GRAS status granted in 2014.

STRUCTURE

Molecular Composition

FORMULA
C₇₈H₁₂₃N₂₃O₂₃S₂
MOL. WEIGHT
1815.12 Da
SEQUENCE LENGTH
16 amino acids
ORIGIN
HGH fragment 176–191
IGF-1 EFFECT
None (selective lipolysis)
DEVELOPMENT
Metabolin (terminated 2007)
AMINO ACID CHAIN VISUALIZATION
Y
Tyr
N-terminal (modified Phe→Tyr)
NH-CO
L
Leu
hydrophobic core
NH-CO
R
Arg
charge, receptor interaction
NH-CO
I
Ile
hydrophobic stability
NH-CO
V
Val
beta-adrenergic upregulation
NH-CO
Q
Gln
lipolysis signalling
NH-CO
L
Leu
C-terminal region
SEQUENCEY-L-R-I-V-Q-L
MECHANISMS

How It Works

🔥
β-3 Adrenergic Receptor Upregulation
AOD-9604 stimulates lipolysis primarily through upregulation of beta-3 adrenergic receptors on adipocytes. β3-AR activation increases cAMP, which activates hormone-sensitive lipase (HSL) to hydrolyse stored triglycerides. Unlike full HGH, this lipolytic effect does not require IGF-1 signalling.
🧬
Lipogenesis Inhibition
Beyond stimulating fat breakdown, AOD-9604 inhibits de novo lipogenesis — the synthesis of new fatty acids from glucose. In vitro studies using isolated adipocytes show simultaneous increases in fat oxidation and reductions in fat synthesis, creating a dual anti-obesity mechanism at the cellular level.
🛡
No IGF-1 or Glucose Effects
The critical safety differentiator from full HGH: AOD-9604 does not stimulate IGF-1 production and does not cause glucose intolerance or insulin resistance. Human trials confirmed absence of IGF-1 elevation and normal glucose tolerance, making it safer for metabolic research than HGH itself.
🔬
Cartilage & Joint Benefits (Emerging)
Emerging preclinical data suggests AOD-9604 may have cartilage-regenerative properties beyond its metabolic effects. Studies show it stimulates chondrocyte differentiation and proteoglycan synthesis. This unexpected benefit is being investigated for osteoarthritis — a separate research direction from its original fat-loss development.
OVERVIEW

Research Overview

AOD-9604 was developed at Monash University, Australia, by researchers who identified that the lipolytic properties of growth hormone resided in its C-terminal region (residues 177–191). This selective profile is its key differentiator from HGH: it does not elevate IGF-1, it does not affect insulin signaling, and the FDA has granted it GRAS (Generally Recognized as Safe) status as a food ingredient in 2014.

Mechanism of Action

// SELECTIVE LIPOLYSIS via β3-AR PATHWAY

AOD-9604 stimulates lipolysis in adipocytes through a beta-3 adrenergic receptor-like mechanism — independent of the IGF-1 pathway used by full HGH. It activates hormone-sensitive lipase, triggering triglyceride hydrolysis.

// LIPOGENESIS INHIBITION

Inhibits fatty acid synthase (FAS) expression in adipose tissue, reducing de novo lipogenesis. This dual action creates a net negative fat balance.

// CARTILAGE REPAIR

Independently stimulates proteoglycan synthesis in cartilage and has been investigated for osteoarthritis treatment via intra-articular injection.

SEQUENCE

Amino Acid Sequence

Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe
DOSAGE

Dosage & Administration

INJECTABLE (SUBCUTANEOUS)
DOSE
300–500 mcg/day
FREQUENCY
Once daily, fasted (morning or pre-workout)
NOTES
Most studied route. Administer fasted — food blunts lipolytic response. Inject near fat-dense areas (abdomen) in some protocols, though systemic effect is likely dominant. Reconstitute in bacteriostatic water.
ORAL
DOSE
1 mg/day (nutraceutical dose)
FREQUENCY
Once daily
NOTES
AOD-9604 received Generally Recognised As Safe (GRAS) status in the US as a nutraceutical. Oral bioavailability is lower than injection but demonstrated in human trials. Used in supplement formulations at this dose.

AOD-9604 is the C-terminal fragment (residues 176–191) of human growth hormone, with tyrosine replacing phenylalanine at the N-terminal. It retains HGH's lipolytic properties without stimulating IGF-1 production or causing glucose intolerance — a key safety advantage over full HGH. Phase 2b human trials demonstrated weight loss, but Phase 3 failed to show sufficient effect for drug approval.

CYCLING

Cycle Duration Guide

ON CYCLE
12–16 weeks on
OFF CYCLE
4–8 weeks off

Longer cycles are common given the modest effect size and lack of receptor desensitisation concerns. AOD-9604 does not appear to downregulate beta-3 adrenergic receptors with chronic use. Best results reported when combined with caloric deficit and exercise. As a nutraceutical ingredient it has been used continuously at lower oral doses.

NOTES

Research Notes

Phase 2b/3 clinical trials in Australia showed dose-dependent fat mass reduction without changes in lean mass, IGF-1, or glucose metabolism. FDA GRAS status granted 2014. Cartilage repair Phase 2 showed significant WOMAC improvements in knee OA patients.

Quick Reference
FORMULAC₇₈H₁₂₃N₂₃O₂₃S₂
MOL. WEIGHT1,817.12 Da
LENGTH16 amino acids
ORIGINSynthetic fragment of human growth hormone (hGH residues 177–191); Monash University
HALF-LIFE~30 minutes (subcutaneous injection)
SOLUBILITYReconstitute with bacteriostatic water; stable in solution for 30 days at 4°C
CAS NO.221231-10-3
STATUSResearch Only
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TAGS
fat losslipolysisHGH fragmentanti-obesitycartilage repair