Best Peptides for Metabolic Research

Metabolic research covers several distinct control points in energy homeostasis: incretin and glucagon receptor signaling, mitochondrial signaling, nuclear-receptor control of oxidative metabolism, amylin-mediated satiety and adipocyte lipolysis. Each compound below acts on a different control point, so choosing the right tool depends on the question your study is asking.

This guide summarizes the published mechanisms and preclinical findings for five compounds BioSim supplies for metabolic research. All are sold for laboratory research only; they are not medicines, are not for human or veterinary use, and nothing here describes administration to people.

Top Metabolic Research Peptides

1. Retatrutide: GIP, GLP-1 and Glucagon Receptor Triple Agonist

Retatrutide (LY3437943) is a single peptide with agonist activity at the glucagon, GIP and GLP-1 receptors. In vitro it showed balanced glucagon and GLP-1 receptor activity with greater GIP receptor activity. In obese mice it decreased body weight and improved glycemic control, and the authors attributed the effect to reduced calorie intake (GIP and GLP-1 receptors) combined with increased energy expenditure (glucagon receptor) (Coskun et al., 2022). That makes it a useful comparator for single and dual incretin agonists. Our retatrutide research guide covers the receptor pharmacology in detail and compares it with semaglutide and tirzepatide.

Research Retatrutide 30mg → | Retatrutide 60mg →

2. MOTS-c: A Mitochondrial-Derived Peptide

MOTS-c is a 16-amino-acid peptide encoded by a short open reading frame in the mitochondrial 12S rRNA gene. In the original report, its main target organ appeared to be skeletal muscle; its cellular actions inhibited the folate cycle and de novo purine biosynthesis, leading to AMPK activation, and MOTS-c prevented diet-induced obesity and insulin resistance in mice (Lee et al., 2015). Later work showed that MOTS-c translocates to the nucleus under metabolic stress in an AMPK-dependent manner and regulates nuclear genes, including those with antioxidant response elements (Kim et al., 2018).

MOTS-c has also been studied in aging mice. It enhanced physical performance in young, middle-aged and old mice, and in humans exercise increased endogenous MOTS-c levels in skeletal muscle and circulation (Reynolds et al., 2021). For a comparison with NAD+ in mitochondrial research, see our NAD+ vs MOTS-c comparison.

Research MOTS-c 40mg →

3. SLU-PP-332: A Synthetic ERR Agonist

SLU-PP-332 is a synthetic small molecule, not a peptide. It is an agonist at all three estrogen-related receptors (ERRα, β and γ), with the highest potency at ERRα. In a skeletal muscle cell line it increased mitochondrial function and cellular respiration, and in mice it increased type IIa oxidative muscle fibers and exercise endurance through an ERRα-dependent acute aerobic exercise gene program (Billon et al., 2023). In diet-induced obese and ob/ob mice, it increased energy expenditure and fatty acid oxidation, decreased fat mass accumulation and improved insulin sensitivity (Billon et al., 2024).

Research SLU-PP-332 5mg →

4. Cagrilintide: A Long-Acting Amylin Analog

Amylin is a 37-amino-acid pancreatic β-cell hormone. Its receptors are multisubunit G protein-coupled receptors formed when a core receptor protein is co-expressed with receptor activity-modifying proteins, producing several receptor subtypes. Amylin acts mainly in the circumventricular organs of the brain and interacts with other metabolic hormones such as cholecystokinin and leptin (Hay et al., 2015). Native amylin readily forms amyloid fibrils, which complicates analog design. Cagrilintide was developed as a stable, lipidated, long-acting amylin analog through structure-activity work aimed at that problem (Kruse et al., 2021). It offers a non-incretin route into satiety signaling and is often studied alongside GLP-1 receptor agonists.

Research Cagrilintide 10mg →

5. AOD-9604: A Lipolytic Fragment of Human Growth Hormone

AOD-9604 is a synthetic peptide derived from the C-terminal lipolytic domain of human growth hormone (hGH). Researchers searching for AOD-9604 as a fat-loss peptide will find that the published data are preclinical. In obese mice, both hGH and AOD-9604 reduced body weight gain, increased fat oxidation and increased plasma glycerol, an index of lipolysis. Unlike hGH, AOD-9604 did not induce hyperglycemia or reduce insulin secretion, did not compete for the hGH receptor and did not induce cell proliferation in hGH receptor-expressing cells (Heffernan et al., 2001b).

A companion study found that both compounds increased β3-adrenergic receptor RNA in fat of obese mice. Long-term effects were lost in β3-adrenergic receptor knockout mice, yet AOD-9604 still increased energy expenditure and fat oxidation acutely in those animals, so the authors concluded that its lipolytic action is not mediated directly through that receptor (Heffernan et al., 2001a). In obese Zucker rats, AOD-9604 reduced body weight gain and increased adipose lipolytic activity without an adverse effect on insulin sensitivity (Ng et al., 2000).

Research AOD-9604 5mg →

Building a Metabolic Research Pipeline

These compounds act at different levels, which makes multi-arm designs possible:

• Receptor-level incretin and glucagon signaling: retatrutide, compared against single or dual agonists.
• Mitochondrial signaling: MOTS-c, with AMPK activation and nuclear gene regulation as measurable endpoints.
• Nuclear-receptor control of oxidative metabolism: SLU-PP-332, with ERRα dependence testable in knockout or knockdown models.
• Amylin-mediated satiety: cagrilintide, as a mechanism separate from the incretin receptors.
• Adipocyte lipolysis: AOD-9604, with glycerol release and fat oxidation as endpoints.

Most of the in vivo data above come from mice and rats, so translating findings needs care. Our guide to mitochondrial function and energy metabolism covers related bioenergetics assays. Every lot is third-party tested, with identity confirmed by mass spectrometry, and the certificates are published on our COA page.

Browse all Metabolic Research peptides →

References

1. Billon C, Sitaula S, Banerjee S, et al. (2023). Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity. ACS chemical biology, 18(4), 756-771. PMID: 36988910 · DOI: 10.1021/acschembio.2c00720
2. Billon C, Schoepke E, Avdagic A, et al. (2024). A Synthetic ERR Agonist Alleviates Metabolic Syndrome. The Journal of pharmacology and experimental therapeutics, 388(2), 232-240. PMID: 37739806 · DOI: 10.1124/jpet.123.001733
3. Coskun T, Urva S, Roell WC, et al. (2022). LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell metabolism, 34(9), 1234-1247.e9. PMID: 35985340 · DOI: 10.1016/j.cmet.2022.07.013
4. Hay DL, Chen S, Lutz TA, et al. (2015). Amylin: Pharmacology, Physiology, and Clinical Potential. Pharmacological reviews, 67(3), 564-600. PMID: 26071095 · DOI: 10.1124/pr.115.010629
5. Heffernan M, Summers RJ, Thorburn A, et al. (2001a). 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, 142(12), 5182-9. PMID: 11713213 · DOI: 10.1210/endo.142.12.8522
6. Heffernan MA, Thorburn AW, Fam B, et al. (2001b). Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 25(10), 1442-9. PMID: 11673763 · DOI: 10.1038/sj.ijo.0801740
7. Kim KH, Son JM, Benayoun BA, et al. (2018). The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. Cell metabolism, 28(3), 516-524.e7. PMID: 29983246 · DOI: 10.1016/j.cmet.2018.06.008
8. Kruse T, Hansen JL, Dahl K, et al. (2021). Development of Cagrilintide, a Long-Acting Amylin Analogue. Journal of medicinal chemistry, 64(15), 11183-11194. PMID: 34288673 · DOI: 10.1021/acs.jmedchem.1c00565
9. Lee C, Zeng J, Drew BG, et al. (2015). The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell metabolism, 21(3), 443-54. PMID: 25738459 · DOI: 10.1016/j.cmet.2015.02.009
10. Ng FM, Sun J, Sharma L, et al. (2000). Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Hormone research, 53(6), 274-8. PMID: 11146367 · DOI: 10.1159/000053183
11. Reynolds JC, Lai RW, Woodhead JST, et al. (2021). MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature communications, 12(1), 470. PMID: 33473109 · DOI: 10.1038/s41467-020-20790-0

Research These Compounds: High-purity research peptides available from BioSim: Retatrutide 30mg, AOD-9604, MOTS-c, SLU-PP-332. All 99%+ purity by HPLC; available certificates are published on our COA page.