Key findings
- Analytical work identified the peptide as the C-terminal fragment of human growth hormone from residues 177 to 191 with an additional tyrosine at the N-terminus, and resolved six metabolites after incubation in serum and urine. [1]
- In isolated rat adipose tissue the related 177 to 191 domain stimulated hormone-sensitive lipase and inhibited acetyl coenzyme A carboxylase, in the same manner the authors observed for intact growth hormone. [2]
- In beta-3 adrenergic receptor knockout mice the body weight and lipolysis changes seen in wild-type mice did not occur, although both the fragment and intact growth hormone raised beta-3 adrenergic receptor transcript levels. [3]
- Unlike intact growth hormone, neither the 177 to 191 domain designated AOD9401 nor the tyrosine-extended peptide changed insulin resistance or glucose tolerance in the chronic experiments in obese Zucker rats. [2][4]
Identity and structure
- Sequence region
- The carboxyl-terminal fragment of human growth hormone spanning residues 177 to 191, with an additional tyrosine residue at the N-terminus [1]
- Related construct
- AOD9401 is the same 177 to 191 lipolytic domain prepared by solid-phase peptide synthesis, reported without the added N-terminal tyrosine; it is a distinct material from the one this profile is named for [2][1]
- Stable metabolite
- A metabolite of the sequence CRSVEGSCG was quantified in serum and reported as significantly more stable than the other metabolites or the parent peptide [1]
- Form as supplied
- Sterile lyophilized powder
Mechanism as studied
The earliest work frames the fragment as a lipolytic domain rather than a growth hormone substitute. In isolated rat adipose tissue the synthesized 177 to 191 domain stimulated hormone-sensitive lipase, inhibited acetyl coenzyme A carboxylase and mimicked the effect of intact growth hormone on diacylglycerol release in adipocytes. [2]
The knockout work then separates two things that had been conflated. Both the fragment and intact growth hormone raised the repressed beta-3 adrenergic receptor transcript levels of obese mice toward the levels of lean mice, yet in mice lacking that receptor the weight and lipolysis changes did not appear, while in an acute experiment the fragment still raised energy expenditure and fat oxidation in those same knockout mice. The authors conclude the lipolytic action is not mediated directly through the beta-3 adrenergic receptor. [3]
Analytical work supplies the identity rather than a mechanism, resolving the peptide against a urine method and characterizing its degradation in serum and urine, which is the basis for distinguishing parent peptide from metabolite in a supplied material. [1]
Research findings
- System
- Isolated rat adipose tissues and adipocytes; the material is the synthesized 177 to 191 domain designated AOD9401, not the tyrosine-extended peptide
- Measured
- Hormone-sensitive lipase activity, acetyl coenzyme A carboxylase activity and diacylglycerol release
- Reported
- Lipase activity was stimulated and acetyl coenzyme A carboxylase inhibited in a manner similar to intact growth hormone, and the effect on diacylglycerol release was mimicked. [2]
- System
- Obese Zucker rats over 20 days; the material is the synthesized 177 to 191 domain designated AOD9401
- Measured
- Body weight gain, adipocyte diameter, insulin resistance and glucose tolerance
- Reported
- Body weight gain was reduced and average adipocyte diameter decreased from 110 to 80 micrometres; unlike intact growth hormone the domain did not induce insulin resistance or glucose intolerance. [2]
- System
- Obese Zucker rats over 19 days, with euglycemic clamp measurements
- Measured
- Body weight gain, lipolytic activity in adipose tissue and insulin sensitivity
- Reported
- Body weight gain was reduced by more than half relative to control, adipose lipolytic activity was increased, and the clamp showed no adverse change in insulin sensitivity, in contrast to intact growth hormone. [4]
- System
- Obese mice and beta-3 adrenergic receptor knockout mice, with wild-type controls, over a 14 day chronic study
- Measured
- Body weight, body fat, beta-3 adrenergic receptor transcript levels, lipolysis, energy expenditure and fat oxidation
- Reported
- Body weight and body fat fell in obese mice and the repressed receptor transcript levels rose toward lean levels; in knockout mice the weight and lipolysis changes did not occur, while an acute experiment still raised energy expenditure and fat oxidation. [3]
- System
- Solid-phase extraction method validated in urine, with incubation of the peptide in serum and in urine
- Measured
- Limit of detection, linearity, precision, specificity and recovery, and the identity of degradation products
- Reported
- The method reached a limit of detection of 50 pg per millilitre with recovery of 62 percent and precision below 20 percent; six metabolites were identified, of which CRSVEGSCG was the single stable one quantified in serum. [1]
Handling for in-vitro work
- Solvent in the cited work
- The lipolytic domain was prepared by solid-phase peptide synthesis and applied to isolated adipose tissue preparations in the assay medium [2]
- Stability
- The parent peptide degraded in serum and in urine in the cited analytical work, so a stability check belongs in the method record for any incubation longer than the assay [1]
- Storage
- Lyophilized at −20 °C, dark and dry; reconstituted aliquots kept cold and used promptly
Open questions
- Two of the rodent reports used AOD9401, the 177 to 191 domain without the added N-terminal tyrosine, so the cited work does not establish that the two constructs behave identically.
- A fragment does not inherit the properties of the intact protein, and the cited work does not report a receptor through which the fragment acts.
- The cited work does not establish a composition standard for material identified only by a trade name, and the analytical report describes vials of uncertain provenance rather than a characterized reference lot.
Lot records
Check the record for the exact material you order. A published paper and a batch certificate answer different questions.
No published lot is available for this exact compound name.
Read a certificate of analysis ↗References
- Cox HD, Smeal SJ, Hughes CM, et al. Detection and in vitro metabolism of AOD9604. Drug testing and analysis. 2015.
- Ng FM, Jiang WJ, Gianello R, et al. Molecular and cellular actions of a structural domain of human growth hormone (AOD9401) on lipid metabolism in Zucker fatty rats. Journal of molecular endocrinology. 2000.
- Heffernan M, Summers RJ, Thorburn A, et al. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology. 2001.
- Ng FM, Sun J, Sharma L, et al. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Hormone research. 2000.
Publication records fetched from PubMed on 2026-09-20. Profile text reviewed 2026-09-20.