5-Amino-1MQ vs MOTS-c
5-Amino-1MQ is a small molecule that blocks the enzyme NNMT, mainly studied in fat tissue, while MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA that acts mainly on skeletal muscle through AMPK. Both have reversed diet-induced obesity in mice and both improved ageing muscle in old mice, but they start from different tissues and different pathways. MOTS-c also has human data on the body’s own levels; 5-Amino-1MQ has none yet. Here is how they compare.
Findings
- 5-Amino-1MQ inhibits nicotinamide N-methyltransferase (NNMT). In fat cells it raised NAD+ and SAM and suppressed fat formation; in diet-induced obese mice it cut body weight, fat mass and adipocyte size over 11 days without changing food intake (2018).
- MOTS-c is encoded within the mitochondrial 12S rRNA gene. It inhibits the folate cycle, activating AMPK, and prevented diet-induced obesity and insulin resistance in mice (2015).
- In sedentary young men, exercise raised MOTS-c in skeletal muscle 11.9-fold and in blood 1.6-fold during the session (2021).
- Both have aged-mouse data: 5-amino-1MQ raised grip strength about 40% in 22-to-24-month-old mice (2024); MOTS-c helped 22-month-old mice run about twice as long (2021).
What is 5-Amino-1MQ?
5-Amino-1MQ (5-amino-1-methylquinolinium) is a small aromatic molecule, not a peptide. Its target, NNMT, transfers a methyl group from S-adenosylmethionine (SAM) to nicotinamide, consuming an NAD+ precursor and the cell’s main methyl donor. NNMT is raised in the fat and liver of obese and diabetic mice, and knocking it down protected against diet-induced obesity by increasing energy expenditure (Kraus et al., Nature, 2014). In people, fat-tissue NNMT expression tracked insulin resistance in a surgical cohort of 199 patients and fell with exercise and bariatric surgery (Kannt et al., Diabetologia, 2015). The compound’s background is in 5-Amino-1MQ: What the NNMT Research Actually Covers.
The research
In its 2018 characterisation, 5-amino-1MQ crossed cell membranes readily, spared related methyltransferases and NAD+ salvage enzymes, and in cultured fat cells raised NAD+ and SAM while suppressing lipogenesis. Diet-induced obese mice treated for 11 days lost weight progressively, with lower white fat mass, adipocytes more than 30% smaller and total cholesterol about 30% lower; food intake did not change and no adverse effects were seen (Neelakantan et al., Biochem Pharmacol, 2018).
In 24-month-old mice recovering from a muscle injury, 5-amino-1MQ activated muscle stem cells, nearly doubled regenerating fibre size and raised peak torque by about 70% (Neelakantan et al., Biochem Pharmacol, 2019). Given from 22 to 24 months of age, it raised grip strength about 40% over sedentary controls, against 20% for exercise alone and 60% for the two combined (Dimet-Wiley et al., Sci Rep, 2024). No human trial has been published.
What is MOTS-c?
MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) is a 16-amino-acid peptide coded by a short reading frame inside mitochondrial DNA, a rare case of the mitochondrial genome sending a hormone-like signal. Its main target appears to be skeletal muscle. In cells it inhibits the folate cycle and the de novo purine synthesis tied to it, building up the metabolite AICAR and activating AMPK, the cell’s energy sensor (Lee et al., Cell Metab, 2015). Under stress it moves into the nucleus and regulates nuclear genes (Reynolds et al., Nat Commun, 2021). The basics are in What Is MOTS-c?
The research
In mice, MOTS-c treatment prevented both age-dependent and high-fat-diet-induced insulin resistance and diet-induced obesity, and raised AMPK activation and GLUT4 expression in muscle (Lee et al., 2015). In 2021, two weeks of MOTS-c improved treadmill performance in middle-aged and old mice, with 22-month-old mice running about twice as long; treatment started late in life, at around 24 months, improved physical capacity and healthspan (Reynolds et al., 2021).
The human work measures the body’s own MOTS-c rather than giving it. In sedentary young men cycling, muscle MOTS-c rose 11.9-fold after exercise and blood levels 1.6-fold during it (Reynolds et al., 2021). Circulating MOTS-c is lower in older men, although muscle MOTS-c was about 1.5-fold higher in middle-aged and older men than in young men (D’Souza et al., Aging, 2020). In 125 adults without diabetes, plasma MOTS-c was higher in those with metabolic syndrome and tracked liver fat (Sequeira et al., Biochim Biophys Acta Gen Subj, 2021). More is in MOTS-c: Exercise, Heat and the Mitochondrial Signal.
How do 5-Amino-1MQ and MOTS-c compare side by side?
| Question | 5-Amino-1MQ | MOTS-c |
|---|---|---|
| What is it? | Synthetic small molecule (methylquinolinium) | Mitochondrial-derived peptide |
| Size | Not a peptide | 16 amino acids |
| Main research area | Fat tissue, obesity, aged muscle repair | Insulin sensitivity, exercise capacity, ageing |
| Mechanism | Blocks NNMT; spares NAD+ precursor and SAM | Folate cycle, AICAR, AMPK; nuclear gene regulation |
| Primary tissue | White fat (plus liver, aged muscle) | Skeletal muscle |
| Human evidence | None published | Endogenous levels only (exercise, age, liver fat) |
| Forms we supply | 50 mg vial | 10 mg and 40 mg vials |
Which one fits which research question?
- Fat-cell metabolism, adipocyte size and methyl-donor balance: 5-Amino-1MQ, which acts on the enzyme most raised in obese fat tissue.
- Muscle glucose uptake, AMPK signalling and exercise capacity: MOTS-c, whose effects centre on skeletal muscle and which the body itself releases during exercise.
- Ageing muscle: both. 5-Amino-1MQ has the regeneration-after-injury and grip-strength data; MOTS-c has running capacity and late-life healthspan data.
Can 5-Amino-1MQ and MOTS-c be studied together?
Yes. The two arrive at metabolism from separate tissues and separate pathways, NNMT in fat for one and the folate cycle and AMPK in muscle for the other, so a design using both keeps two distinguishable variables. A shared thread is that both research groups paired their compound with exercise in old mice. That rationale is drawn from each compound’s own literature; we found no published study of the combination. MOTS-c is also part of the Mitochondrial Energy stack with SS-31 and glutathione, and is compared with its stack partners in MOTS-c vs SS-31 and NAD+ vs MOTS-c. See also NAD+ vs 5-Amino-1MQ.
How are 5-Amino-1MQ and MOTS-c supplied?
5-Amino-1MQ comes as a 50 mg lyophilised vial and MOTS-c as 10 mg and 40 mg lyophilised vials. Both are reconstituted with bacteriostatic water: see the 5-Amino-1MQ reconstitution guide and the MOTS-c reconstitution guide. Certificates of analysis are on the lab reports page, and every order ships from within Canada by Canada Post Xpresspost.
5-Amino-1MQ and MOTS-c are supplied for laboratory research use only. The treatment studies above were done in cells and mice; the human MOTS-c studies measured naturally occurring levels.
Frequently asked questions
What is the difference between 5-Amino-1MQ and MOTS-c?
5-Amino-1MQ is a small molecule that inhibits NNMT, an enzyme raised in obese fat tissue. MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA that acts mainly on skeletal muscle by activating AMPK through the folate cycle.
Is 5-Amino-1MQ stronger than MOTS-c?
They have not been compared head to head. Each reversed diet-induced obesity in mice by a different route, and each improved ageing muscle in old mice. Neither has a published human treatment trial.
Is 5-Amino-1MQ a peptide?
No. 5-Amino-1MQ is a methylquinolinium, a small aromatic molecule. MOTS-c is a peptide of 16 amino acids.
Can 5-Amino-1MQ and MOTS-c be studied together?
Yes. One acts on NNMT in fat tissue and the other on the folate cycle and AMPK in muscle, so a study using both keeps two distinguishable variables. No published study has tested the combination.
Where can I buy 5-Amino-1MQ and MOTS-c in Canada?
Vistara Labs supplies 5-Amino-1MQ as a 50 mg vial and MOTS-c as 10 mg and 40 mg vials, plus the Mitochondrial Energy stack, shipped from within Canada by Canada Post Xpresspost.
Product details from vistaralabs.ca, October 2026. Sources: Kraus D et al. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature. 2014. PMID 24717514. Kannt A et al. Association of nicotinamide-N-methyltransferase mRNA expression in human adipose tissue and the plasma concentration of its product, 1-methylnicotinamide, with insulin resistance. Diabetologia. 2015. PMID 25596852. Neelakantan H et al. Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice. Biochem Pharmacol. 2018. PMID 29155147. Neelakantan H et al. Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle. Biochem Pharmacol. 2019. PMID 30753815. Dimet-Wiley AL et al. Nicotinamide N-methyltransferase inhibition mimics and boosts exercise-mediated improvements in muscle function in aged mice. Sci Rep. 2024. PMID 38969654. Lee C et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015. PMID 25738459. Reynolds JC et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021. PMID 33473109. D’Souza RF et al. Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition. Aging (Albany NY). 2020. PMID 32182209. Sequeira IR et al. Plasma mitochondrial derived peptides MOTS-c and SHLP2 positively associate with android and liver fat in people without diabetes. Biochim Biophys Acta Gen Subj. 2021. PMID 34419510.
More on this: Weight Loss & Metabolism Research.
All products supplied by Vistara Labs are intended for laboratory research use only. They are not drugs, are not approved for human or veterinary use, and are not intended to diagnose, treat, cure or prevent any condition. Nothing on this page constitutes medical advice or guidance for use in humans.
