The Fat Loss Stack: AOD-9604 + Tesamorelin + MOTS-c
Last updated: 2026-02-20
The AOD-9604, Tesamorelin, and MOTS-c fat loss stack combines three peptides that attack fat metabolism from distinct angles: direct lipolysis, growth hormone-mediated visceral fat mobilization, and mitochondrial metabolic activation. This multi-pathway approach targets fat loss without the significant appetite suppression associated with GLP-1 agonists, making it suitable for individuals who want to maintain normal eating patterns while optimizing fat metabolism.
Research suggests that AOD-9604 (the fat-burning fragment of human growth hormone) stimulates lipolysis and inhibits lipogenesis without the diabetogenic or growth-promoting effects of full GH.[1] Tesamorelin, an FDA-approved GHRH analog, specifically targets visceral adipose tissue through endogenous GH elevation.[2] MOTS-c, a mitochondrial-derived peptide, enhances metabolic function by activating AMPK and improving glucose utilization and fatty acid oxidation.[3]
This guide details the evidence-based rationale, complete dosing protocol, synergy mechanisms, expected timeline, and safety information for this triple fat-loss stack. All information is for educational purposes only. Consult a qualified healthcare professional before beginning any peptide protocol.
Compounds in This Stack
AOD-9604
Lipolysis stimulation, lipogenesis inhibition, HGH fat-burning fragment
AOD-9604 (Advanced Obesity Drug) is a synthetic peptide fragment corresponding to amino acids 177–191 of the C-terminal end of human growth hormone, with an added tyrosine at the N-terminus. It was specifically developed to isolate the fat-reducing properties of GH without the growth-promoting, diabetogenic, or IGF-1-elevating effects of full-length growth hormone.[1]
Mechanism in this stack: AOD-9604 stimulates the beta-3 adrenergic receptor pathway to promote lipolysis (breakdown of stored fat into free fatty acids) and simultaneously inhibits lipogenesis (the creation of new fat). Importantly, it does not affect blood glucose levels, IGF-1 levels, or insulin sensitivity—making it metabolically neutral beyond its fat-specific effects. It serves as the direct fat-mobilization agent in this stack.
| Parameter | Detail |
|---|---|
| Research Dosage | 250–500 mcg per day |
| Timing | Morning, fasted state (before breakfast) |
| Administration | Subcutaneous injection (abdominal area) |
| Half-Life | Short-acting; effects mediated through receptor activation |
| IGF-1 Impact | None (does not elevate IGF-1 or affect glucose) |
Tesamorelin
GHRH analog, visceral fat targeting, endogenous GH elevation
Tesamorelin is a synthetic 44-amino-acid GHRH analog that stimulates pulsatile growth hormone release from the anterior pituitary. It is FDA-approved (Egrifta) for reducing visceral adipose tissue in HIV-associated lipodystrophy—the only peptide with direct regulatory approval for targeted fat reduction.[2]
Mechanism in this stack: While AOD-9604 provides direct lipolysis stimulation, tesamorelin addresses fat loss through a different pathway: endogenous GH elevation. The resulting growth hormone promotes visceral fat mobilization specifically, as visceral fat deposits have a higher density of GH receptors compared to subcutaneous fat. Tesamorelin also improves lipid profiles, reduces triglycerides, and may improve liver fat content (hepatic steatosis). It provides the visceral-fat-specific component of this triple stack.
| Parameter | Detail |
|---|---|
| Research Dosage | 1–2 mg per day |
| Timing | Evening, fasted (30–60 min before bed) |
| Administration | Subcutaneous injection (abdominal area) |
| Half-Life | 26–38 minutes |
| Key Trial Data | 15–18% reduction in visceral adipose tissue in Phase III trials |
MOTS-c
Mitochondrial metabolic activator, AMPK signaling, glucose regulation
MOTS-c (Mitochondrial Open Reading Frame of the Twelve S rRNA Type-c) is a 16-amino-acid mitochondrial-derived peptide (MDP) that functions as a metabolic regulator. Discovered by Dr. Changhan Lee in 2015, MOTS-c is encoded in the mitochondrial genome and has been shown to regulate metabolic homeostasis by activating AMP-activated protein kinase (AMPK), a master metabolic switch.[3]
Mechanism in this stack: MOTS-c serves as the metabolic enhancer in this fat-loss stack. By activating AMPK, it shifts cellular metabolism toward fat oxidation and glucose utilization, mimicking some of the metabolic benefits of exercise. MOTS-c improves insulin sensitivity, enhances fatty acid oxidation in skeletal muscle, and promotes metabolic flexibility—the ability to switch between fuel sources efficiently. In animal studies, MOTS-c prevented diet-induced obesity and improved glucose tolerance. It provides the metabolic optimization layer that complements the direct lipolysis (AOD-9604) and visceral fat targeting (tesamorelin).
| Parameter | Detail |
|---|---|
| Research Dosage | 5–10 mg per injection |
| Frequency | 3x per week (e.g., Monday, Wednesday, Friday) |
| Administration | Subcutaneous injection |
| Half-Life | Research data limited; effects mediated through AMPK activation |
| Key Research | Lee et al. 2015: prevented diet-induced obesity in mice |
How They Work Together
The AOD-9604, Tesamorelin, and MOTS-c fat loss stack targets fat metabolism through three distinct and complementary pathways, creating a comprehensive approach to body fat reduction that does not rely on appetite suppression.
Three Pathways to Fat Loss
- AOD-9604 → Direct lipolysis: Stimulates beta-3 adrenergic receptors to break down stored fat into free fatty acids, and inhibits new fat formation (lipogenesis). Does not affect GH, IGF-1, or glucose metabolism.[1]
- Tesamorelin → GH-mediated visceral fat mobilization: Elevates endogenous GH to preferentially mobilize visceral (deep abdominal) fat, the most metabolically dangerous fat depot.[2]
- MOTS-c → Metabolic activation: Activates AMPK to enhance fatty acid oxidation, improve glucose utilization, and increase metabolic flexibility—effectively improving the body’s ability to burn the fat that AOD-9604 and tesamorelin have mobilized.[3]
Mobilization + Oxidation Synergy
A critical concept in fat metabolism is that mobilizing fat (lipolysis) and burning fat (oxidation) are separate processes. AOD-9604 and tesamorelin excel at mobilizing fat from adipose stores into the bloodstream as free fatty acids. However, if those fatty acids are not oxidized (burned for energy), they can be re-esterified and stored again. MOTS-c addresses this bottleneck by activating AMPK—the enzyme that upregulates fatty acid oxidation in skeletal muscle and other tissues. This mobilization + oxidation combination is why the three-compound stack may be more effective than any two of these peptides alone.
No Appetite Suppression Approach
Unlike the weight loss stack (semaglutide + tesamorelin), which relies heavily on appetite suppression via GLP-1 receptor activation, this fat-loss stack works through metabolic mechanisms that do not significantly reduce appetite. This is a key distinction for individuals who want to maintain normal eating patterns (including adequate protein intake for muscle preservation) while targeting fat stores. The fat-loss stack is better suited for people who are already eating well but want to accelerate fat metabolism, while the weight-loss stack is more appropriate for those who need help controlling caloric intake.
Metabolic Health Beyond Fat Loss
All three compounds offer metabolic benefits beyond direct fat reduction. Tesamorelin improves lipid profiles and reduces triglycerides. MOTS-c improves insulin sensitivity and glucose metabolism. AOD-9604 reduces fat stores without adversely affecting glucose homeostasis. The combined metabolic improvement may reduce cardiovascular risk factors and improve overall metabolic health independently of the scale weight changes.
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Protocol & Dosage Schedule
Dosage Schedule
| Compound | Dosage | Timing | Frequency |
|---|---|---|---|
| AOD-9604 | 250–500 mcg/day | Morning, fasted (before breakfast) | Daily |
| Tesamorelin | 1–2 mg/day | Evening, fasted (30–60 min before bed) | Daily |
| MOTS-c | 5–10 mg/injection | Morning (any time) | 3x per week (e.g., Mon/Wed/Fri) |
Cycle Length
8–12 weeks is the recommended cycle for this fat-loss stack. AOD-9604 is commonly run for 8–12 weeks. Tesamorelin can be run for 12–26 weeks based on FDA-trial protocols. MOTS-c cycling data is more limited, but 8–12 week cycles with 4-week breaks are a reasonable approach. A minimum 4-week off period between full cycles is recommended. Blood work (metabolic panel, IGF-1, fasting glucose) should guide cycle duration.
Timing & Administration
AOD-9604 timing: Administer subcutaneously first thing in the morning on an empty stomach (fasted state). Fasting is important because elevated insulin from food intake can inhibit the lipolytic effects. Wait at least 30 minutes before eating breakfast. Inject in the abdominal area for convenience.
Tesamorelin timing: Administer subcutaneously in the evening, on an empty stomach (at least 2 hours after the last meal). Evening dosing aligns with the natural nocturnal GH pulse. Inject in the abdominal area. The AM/PM split between AOD-9604 and tesamorelin creates a nearly continuous fat-mobilizing stimulus throughout the 24-hour period.
MOTS-c timing: Administer subcutaneously on designated days (e.g., Monday, Wednesday, Friday). Morning administration is preferred to align with the body’s peak metabolic activity period. Can be taken at the same time as AOD-9604 but as a separate injection. MOTS-c does not require fasted-state administration.
Sample daily schedule (MOTS-c day):
- 6:30 AM – Wake up (fasted)
- 6:45 AM – AOD-9604 300–500 mcg subcutaneous (abdomen)
- 6:45 AM – MOTS-c 5–10 mg subcutaneous (separate site; on M/W/F only)
- 7:15 AM – Breakfast (30+ min after AOD-9604)
- 9:00 PM – Last food
- 10:30 PM – Tesamorelin 1–2 mg subcutaneous (fasted)
- 11:00 PM – Sleep
What to Expect
Fat loss from this metabolic stack is more gradual than from appetite-suppressing approaches (like semaglutide) because it does not create a large caloric deficit through appetite reduction. Instead, it enhances the body’s fat-burning machinery. Exercise and a moderate caloric deficit will significantly amplify results.
| Timeframe | Expected Observations |
|---|---|
| Weeks 1–2 | Improved energy levels from MOTS-c metabolic activation. Subtle changes in body temperature or perspiration from enhanced fat oxidation. Improved sleep quality from tesamorelin’s GH effects. Minimal visible fat loss at this stage. |
| Weeks 3–4 | Early body composition changes becoming noticeable. Improved exercise performance and endurance from MOTS-c. Beginning of waist circumference reduction. Improved fasting glucose readings. Enhanced recovery from workouts. |
| Weeks 5–8 | Measurable fat loss, particularly in the abdominal region. Improved lipid panel markers. Visible body composition improvement. Enhanced metabolic flexibility. Continued improvements in exercise capacity and energy. |
| Weeks 8–12 | Significant reduction in visceral fat (measurable on imaging). Sustained body composition improvement. Improved metabolic health markers on blood work. End-of-cycle assessment and blood work. Total fat loss of 4–10 lbs typical when combined with exercise and moderate caloric deficit. |
Safety & Contraindications
Known Side Effects
AOD-9604 reported side effects:
- Generally well-tolerated in clinical studies
- Mild injection site reactions (redness, irritation)
- Headache (infrequent)
- Chest tightness (rare, resolve spontaneously)
- Notably does NOT affect blood glucose, IGF-1, or cause the side effects associated with full-length GH[1]
Tesamorelin reported side effects:
- Injection site reactions (erythema, pruritus, pain)
- Arthralgia (joint pain) from GH elevation
- Peripheral edema (mild water retention)
- Paresthesia (tingling in extremities)
- Potential elevation of fasting glucose (GH is counter-regulatory to insulin)
MOTS-c reported side effects:
- Limited human side effect data (relatively new research compound)
- Injection site reactions
- Preclinical studies have not identified significant adverse effects
- As a naturally occurring mitochondrial peptide, it is expected to have a favorable safety profile, but long-term human data is lacking[3]
Contraindications and Cautions
- Cancer history: Tesamorelin elevates GH and IGF-1, which promote cell proliferation. Avoid in individuals with active cancer or GH-dependent tumors.
- Diabetes: Tesamorelin may elevate blood glucose through GH’s counter-regulatory effects. While AOD-9604 and MOTS-c do not adversely affect glucose (MOTS-c may actually improve it), monitor fasting glucose and HbA1c regularly, especially in diabetic or prediabetic individuals.
- Pregnancy and breastfeeding: No safety data exists. Avoid use entirely.
- Under 25 years old: GH-axis stimulation (tesamorelin) is unnecessary in young adults with naturally high GH levels.
- Pituitary disorders: Tesamorelin acts on the pituitary. Individuals with pituitary tumors or other pituitary conditions should consult an endocrinologist before use.
Monitoring Recommendations
- Blood work every 8–12 weeks: Fasting glucose, HbA1c, IGF-1, lipid panel, liver enzymes, complete metabolic panel
- Body composition: DEXA scan or waist circumference measurements at baseline and every 4–6 weeks to track fat loss objectively
- Blood pressure: Regular monitoring as metabolic changes can affect cardiovascular parameters
Important: Tesamorelin (Egrifta) is FDA-approved for HIV-associated lipodystrophy. AOD-9604 has TGA (Australian) approval for general sale but is not FDA-approved. MOTS-c is a research compound with no regulatory approval. This information is for educational purposes only. Always consult a qualified healthcare professional before beginning any peptide protocol.
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Frequently Asked Questions
References
- Heffernan MA, Thorburn AW, Fam B, et al.. Increase of fat oxidation and weight loss in obese mice by chronic treatment with human growth hormone or a modified C-terminal fragment. International Journal of Obesity, 2001.
- Falutz J, Allas S, Blot K, et al.. Metabolic effects of a growth hormone-releasing factor in patients with HIV. New England Journal of Medicine, 2007.
- Lee C, Zeng J, Drew BG, et al.. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism, 2015.
- Stanley TL, Feldpausch MN, Oh J, et al.. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation. JAMA, 2014.
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Our content is reviewed for accuracy and grounded in peer-reviewed research where available. We do not provide medical advice. Always consult a qualified healthcare professional.