Lipolysis, GH secretagogues, and adipose tissue modulation in obesity models
Weight loss peptide research focuses primarily on compounds that either directly promote lipolysis (fat breakdown) or stimulate growth hormone (GH) secretion, which secondarily drives fat oxidation. AOD-9604 is a modified fragment of the C-terminal portion of human growth hormone (hGH 176–191) that retains the lipolytic activity of GH without its proliferative or diabetogenic effects. CJC-1295 with DAC (Drug Affinity Complex) is a GHRH (growth hormone-releasing hormone) analogue with extended half-life due to albumin binding. Ipamorelin is a selective GH secretagogue that stimulates pulsatile GH release without the cortisol/prolactin side-effects of first-generation GHRPs. A separate, pharmaceutical class — the incretin analogues semaglutide, tirzepatide and retatrutide and the amylin analogue cagrilintide — acts on GLP-1, GIP, glucagon and amylin receptors to regulate appetite and glucose handling; semaglutide and tirzepatide are approved prescription medicines, while research-labelled vials of any of the four are unapproved products sold outside that regulated supply chain and are covered on their own compound pages.
AOD-9604 activates β3-adrenergic receptors in adipose tissue, stimulating lipolysis via cAMP/PKA-mediated phosphorylation of hormone-sensitive lipase (HSL), without binding the IGF-1 receptor. CJC-1295 DAC binds GHRH receptors on pituitary somatotrophs, driving GH synthesis and release; DAC modification enables albumin binding that extends half-life to 6–8 days. Ipamorelin mimics ghrelin at the GHS-R1a receptor, producing selective, pulsatile GH release with minimal effect on ACTH, cortisol, or prolactin.
Модифицированный C-концевой фрагмент гормона роста человека (гГР 177–191). Исследуется по механизмам жировой ткани; не одобрен для терапевтического применения у человека.
Синтетический пентапептид, описанный в 1998 году исследователями Novo Nordisk как селективный агонист рецептора грелина/GH-секретагога. Исследуется в контексте высвобождения гормона роста; не одобрен для терапевтического применения у человека.
Синтетический аналог GHRH(1-29), разработанный ConjuChem; форма с DAC связывается с альбумином и действует несколько дней, форма без DAC (Mod GRF 1-29) — короткого действия. Исследуется для стимуляции оси GH/IGF-1; не одобрен для терапевтического применения у человека.
Агонист рецептора GLP-1, одобренный FDA и EMA как Ozempic, Wegovy и Rybelsus. Семаглутид из исследовательских флаконов — иной, неодобренный продукт, не производимый и не проверяемый как эти препараты, не предназначенный для человека.
Двойной агонист рецепторов GIP/GLP-1, одобренный FDA и EMA как Mounjaro и Zepbound. Тирзепатид из исследовательских флаконов — иной, неодобренный продукт, не производимый и не проверяемый как эти препараты, не предназначенный для человека.
Исследуемый тройной агонист рецепторов GIP/GLP-1/глюкагона (LY3437943) компании Eli Lilly, изучаемый в исследованиях фазы 3; нигде не одобрен как лекарственный препарат и не предназначен для терапевтического применения у человека.
Длительно действующий агонист рецептора амилина (AM833 / NNC0174-0833) компании Novo Nordisk, изучаемый в монотерапии и в комбинации CagriSema; нигде не одобрен как препарат и не предназначен для терапевтического применения у человека.
| Протокол | Пептиды | Длительность | Дозировка | Конечная точка |
|---|---|---|---|---|
| Diet-Induced Obesity Model (DIO) | AOD-9604 | 42 days | 250 µg/kg (rodent) · Once daily SC injection | Body weight (twice weekly), fat mass % (DXA or MRI), adipose tissue lipolysis (glycerol release from explants), serum lipid profile (triglycerides, FFA) |
| GH Secretion Pulse Study | CJC-1295 DAC, Ipamorelin | 28 days | CJC-1295: 300 µg/kg; Ipamorelin: 100 µg/kg · CJC-1295 DAC once weekly; Ipamorelin once daily | GH serum pulsatility (serial sampling every 20 min over 4 hours), IGF-1 serum (ELISA), body composition by DXA at days 0 and 28 |
AOD9604 stimulated lipolysis in adipocytes exclusively via β3-adrenergic receptors without detectable IGF-1 receptor binding, demonstrating a cleaner metabolic profile than full-length hGH in DIO rat models.
PMID 9497040A single injection of CJC-1295 produced GH secretion lasting 6 days and dose-dependent increases in serum IGF-1 of 2–3×, demonstrating the utility of albumin-binding for sustained GHRH-receptor agonism.
PMID 16352683✓Плюсы
- AOD-9604 received FDA GRAS (Generally Recognised As Safe) status for oral use — favourable regulatory safety signal
- CJC-1295 DAC requires only once-weekly dosing due to its 6–8 day half-life — highly convenient vs. daily protocols
- Ipamorelin is the most selective GH secretagogue available: no cortisol, prolactin, or ACTH elevation at standard doses
- CJC-1295 has published Phase I and II human trial data with well-characterised GH/IGF-1 pharmacokinetics
- AOD-9604 selectively activates β3 receptors in fat cells without binding IGF-1 receptors — no anabolic side-effects
- Combination of CJC-1295 + Ipamorelin produces 2–5× greater GH pulse than either compound alone
×Минусы
- All three compounds require subcutaneous injection — no oral route with established human bioavailability
- CJC-1295 substantially raises IGF-1 levels: blood glucose monitoring is advisable, especially for pre-diabetic individuals
- AOD-9604 Phase III obesity trials showed limited efficacy at the doses tested orally — systemic injectable effects differ
- Body composition improvements require consistent use over weeks to months — not a rapid intervention
- EU availability is currently limited: only Particle Peptides consistently stocks all three in 2026
- GH elevation during sleep can disrupt sleep architecture if dosed too close to bedtime
Does AOD-9604 affect blood glucose like GH?
No. AOD-9604 was specifically engineered to lack the diabetogenic and anabolic effects of full-length GH. It does not bind the IGF-1 receptor or significantly alter fasting glucose in published studies, which is a key safety advantage in obesity research.
Why combine CJC-1295 with Ipamorelin rather than use either alone?
CJC-1295 (GHRH analogue) and Ipamorelin (GHS-R agonist) act via distinct receptor pathways that converge on somatotroph GH release. Their combination produces synergistic GH secretion (2–5× AUC vs. monotherapy) while Ipamorelin's selectivity keeps cortisol and prolactin elevations minimal.
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