AOD-9604

Fat Metabolism & Lipolysis

• Stimulates the breakdown of stored fat (lipolysis) in white adipose tissue.
• Inhibits lipogenesis, reducing the formation of new fat cells.
• Promotes release of free fatty acids from adipocytes for energy utilization.
• Demonstrated fat-reducing effects in obese animal models and human adipose tissue samples.

Energy Expenditure & Fat Oxidation

• Increases basal metabolic rate and total energy expenditure in preclinical studies.
• Enhances fat oxidation, shifting metabolism toward fat-burning over carbohydrate use.
• Improves mitochondrial efficiency in fatty acid utilization for energy production.
• Demonstrated metabolic enhancement even in β3-adrenergic receptor-deficient models.

Adrenergic Receptor Modulation

• Upregulates β3-adrenergic receptors in adipose tissue, improving responsiveness to fat-burning signals.
• Restores β3-receptor expression in obese models to levels found in lean subjects.
• May amplify lipolytic signaling pathways without central nervous system stimulation.

Body Composition & Weight Regulation

• Reduces body fat and supports body weight loss in diet-independent animal studies.
• Modest weight loss effect confirmed in short-term human obesity trials.
• Fat loss observed in absence of muscle wasting or growth hormone-like tissue hypertrophy.

Cartilage & Connective Tissue Repair

• Enhances proteoglycan and collagen production in chondrocytes.
• Promotes regeneration of cartilage matrix in osteoarthritis models.
• Improves joint histology and functional recovery in preclinical orthopedic research.
• Often studied for its potential in supporting cartilage health and slowing degeneration.

Growth Hormone Independence & Safety

• Mimics hGH’s lipolytic activity without stimulating IGF-1 or growth-related pathways.
• Does not bind to GH receptors or induce mitogenic or diabetogenic effects.
• Avoids side effects associated with full-length growth hormone (e.g., insulin resistance, edema).
• Confirmed to have no effect on glucose tolerance or insulin sensitivity in human trials.

Clinical Safety & Tolerability

• Tested in over 900 human subjects across multiple placebo-controlled studies.
• Exhibited excellent safety profile with no adverse metabolic or immune effects.
• No anti-peptide antibodies detected in human trials, indicating low immunogenicity.
• Well tolerated across dose ranges; no significant side effect differences from placebo.

To maximize the utility of AOD-9604 in experimental models, researchers often combine it with compounds that enhance fat metabolism, support cartilage regeneration, or complement energy expenditure pathways. These combinations are commonly used in obesity research, metabolic health studies, and tissue regeneration investigations.

Below is a summary of notable AOD-9604 synergies validated in preclinical and early clinical research:

AOD-9604 Synergistic Compounds

Potential Research Use Cases for AOD-9604 Combinations

• Fat Loss & Lipid Metabolism Models:
  AOD-9604 + CJC-1295 (No DAC) / Ipamorelin / 5-Amino-1MQ
  
• Metabolic Health & Insulin Sensitivity:
  AOD-9604 + MOTS-C / Glutathione / NAD⁺
  
• Muscle Preservation & Recovery:
  AOD-9604 + BPC-157 / TB-500
  
• Skin & Body Composition Research:
  AOD-9604 + GHK-Cu / CJC-1295 (No DAC)
  
• Anti-Inflammatory & Regenerative Studies:
  AOD-9604 + Thymosin Alpha-1 / BPC-157
  
  

Stimulates Fat Breakdown (Lipolysis)
AOD-9604 significantly increases the breakdown of stored fat in adipocytes. In both animal studies and adipose tissue assays, this peptide boosted lipolytic activity – leading to the release of fatty acids from fat cells (Ref. 1) (Ref. 3). Notably, human adipose tissue samples exposed to AOD-9604 ex vivo also showed increased lipolysis, indicating a direct fat-burning effect relevant across species (Ref. 1).

Inhibits Fat Formation (Antilipogenic Effects)Alongside stimulating fat breakdown, AOD-9604 reduces lipogenesis, the process by which the body creates and stores fat. Research in obese rodent models demonstrated that AOD-9604 treatment significantly lowered the incorporation of nutrients into new fat in adipose tissue (Ref. 1) (Ref. 10). This dual action – more fat being burned and less fat being made – underlies its potential as an anti-obesity research agent (Ref. 2) (Ref. 3).

Improved Metabolic Health & Insulin Sensitivity: By remodeling adipose tissue and boosting NAD⁺, 5-Amino-1MQ helps normalize metabolic function. Studies report that NNMT inhibition reversed obesity-linked insulin resistance – treated obese mice had improved insulin sensitivity and normalized blood-glucose tolerance to levels of lean healthy mice (Ref. 4) (Ref. 5). These effects were absent in NNMT-knockout animals, confirming the specificity of the mechanism (Ref. 10). In essence, 5-Amino-1MQ enhances glucose uptake and reduces insulin resistance, which may benefit research into type 2 diabetes and metabolic syndrome (Ref. 2) (Ref. 4).

Promotes Weight Loss in Obese Models
Multiple preclinical studies have shown that AOD-9604 can reduce body weight and body fat in obesity models. In obese mice, chronic administration of AOD-9604 led to significantly lower weight gain compared to controls (despite equal food intake) over the course of treatment (Ref. 2) (Ref. 3). After 14 days of injections, treated obese mice had reduced body weight and fat mass, correlating with enhanced fat-metabolism markers (Ref. 2). These results suggest that AOD-9604 can produce weight-loss effects independent of diet changes, making it a compelling tool for obesity research (Ref. 6).

Increases Metabolic Rate & Fat Oxidation
AOD-9604 has been shown to elevate energy expenditure and shift metabolism toward greater fat burning. In acute and sub-chronic tests, AOD-9604 administration increased whole-body energy expenditure and elevated oxidation of fats (and glucose) for fuel in obese models (Ref. 2) (Ref. 3). By enhancing basal metabolic rate and promoting fatty-acid oxidation, AOD-9604 helps the body utilize stored fat as energy, supporting overall fat reduction (Ref. 2).

Beta-3 Adrenergic Pathway Modulation
Research indicates AOD-9604 works, in part, by affecting the adrenergic receptors involved in fat burning. Chronic AOD-9604 treatment was associated with increased β3-adrenergic pathway signaling in white fat tissue and restoration of β3-receptor–linked lipolytic responsiveness in obese mice (Ref. 2). β3-adrenergic receptors are primary mediators of lipolysis in adipocytes; by enhancing β3-linked signaling, AOD-9604 appears to make fat cells more responsive to catecholamine signals that trigger fat breakdown (Ref. 2). In β3-receptor knockout mice, the long-term weight-reducing effect of AOD-9604 was blunted, confirming the importance of this pathway, while some acute oxidation effects suggest additional mechanisms contribute to its action (Ref. 2).

No hGH-Like Side Effects (No IGF-1 Elevation or Cell Proliferation)
AOD-9604 was designed to separate the fat-loss properties of hGH from its growth/trophic effects. Studies have reported that AOD-9604 does not stimulate IGF-1 production and does not exhibit growth-promoting effects associated with full-length hGH (Ref. 4) (Ref. 5). In other words, while it mimics GH’s beneficial fat-metabolism effects, AOD-9604 does not induce cell proliferation, organ growth, or changes in IGF-1 levels seen with hGH therapy (Ref. 4) (Ref. 5).

No Impact on Blood Glucose or Insulin Levels
Unlike hGH, which can antagonize insulin and raise blood sugar, AOD-9604 has shown no negative effect on carbohydrate metabolism in clinical metabolic testing; blood glucose and insulin responses remained unchanged versus placebo (Ref. 4) (Ref. 5). This suggests the peptide promotes fat loss without impairing insulin sensitivity or glycemic control – a crucial distinction for metabolic research, especially in obesity or diabetes contexts (Ref. 4).

Demonstrated Safety in Human Trials
AOD-9604 has undergone testing in humans and exhibited an excellent safety and tolerability profile. A pooled analysis of six randomized, placebo-controlled trials (roughly 900 total subjects) found AOD-9604 was indistinguishable from placebo in terms of adverse effects (Ref. 4). No serious side effects were attributed to the peptide at various doses. Importantly, no anti-AOD-9604 antibodies were detected (Ref. 4). Clinical chemistry panels also showed no deleterious changes in organs or metabolic parameters relative to placebo (Ref. 5). Overall, researchers concluded that AOD-9604 displays a very good safety profile, with none of the typical side effects of full-length hGH (e.g., joint pain, edema, insulin resistance) (Ref. 4) (Ref. 5).

Efficacy in Human Weight-Loss Studies
While primarily documented in animal models, AOD-9604 has also been examined in human obesity trials. In a 12-week randomized clinical trial, overweight subjects receiving AOD-9604 lost more body weight on average than those on placebo (Ref. 6). However, in a subsequent 24-week study, the weight-loss differences were not statistically significant (Ref. 6). Due to this modest efficacy, development as an obesity drug was halted in 2007. Nonetheless, the human trials confirmed AOD-9604’s biological activity (fat loss) and safety in people, supporting its ongoing use in research settings to further explore dosing, delivery, and combinatorial strategies (Ref. 4) (Ref. 5) (Ref. 6).

Cartilage Repair and Regeneration
Beyond fat metabolism, emerging research shows AOD-9604 may play a role in connective tissue repair. Preclinical studies in osteoarthritis models demonstrated that intra-articular AOD-9604 can enhance cartilage regeneration; treated joints had better histological scores and improved function compared to controls, with additional benefit when combined with hyaluronic acid (Ref. 9). Reviews of chondrogenic peptides also summarize these findings and dosing details (Ref. 9).