TLQP-21
A 21-amino-acid VGF peptide that burns fat and curbs weight gain — acting through a complement receptor. A research neuropeptide, not a drug
TLQP-21 is a 21-amino-acid neuropeptide, one of several active pieces cut from a larger precursor called VGF — a granin-like protein packaged in the secretory granules of nerve and endocrine cells. Its name comes from its first residues. Among the many VGF peptides, TLQP-21 is the most studied, and its headline role is metabolic: it is a 'catabolic' peptide that tips the body toward burning energy rather than storing it. Given into the brain of mice it prevents the weight gain of a high-fat diet even when the animals keep overeating, and it drives fat breakdown (lipolysis) directly in fat cells. Remarkably, the receptor it uses for this is the complement C3a receptor (C3aR1) — a receptor better known from the immune system — with a second binding partner, gC1qR, also reported. TLQP-21 does more than manage weight: it sharpens the release of insulin when blood sugar rises, contributes to inflammatory and nerve-injury pain in the spinal cord, protects the stomach lining, and stimulates the pancreas. A catch for drug developers is that the human version of TLQP-21 is a far weaker activator of C3aR than the mouse version, so findings do not translate straight across species. TLQP-21 is studied as a research neuropeptide and a promising obesity target; it is not an approved medicine and has not been given to people as a treatment.
No established human dose Details ↓
Recommended Dosing
No established human dose
TLQP-21 is an endogenous VGF-derived peptide that has never been given to people as a treatment. The work is in animals and cells (including human cells in the dish), where TLQP-21 is given at experimental amounts that do not carry over to people.
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What is it?
VGF is a granin-like protein — a pro-peptide stored in the regulated secretory granules of nerve and neuroendocrine cells and cut into a set of smaller active peptides. TLQP-21, a 21-amino-acid peptide from the C-terminal region of VGF (around residues 556-576), is the most studied of them. It is found throughout the nervous system, the gut and neuroendocrine glands, and it is best known as a catabolic, energy-expending peptide.
The clearest demonstration is in body-weight control. When TLQP-21 is infused chronically into the brain of mice prone to fast weight gain, it selectively blocks the weight gain and the expansion of white fat caused by a high-fat diet — even though the animals eat just as much — while normalising leptin and ghrelin, raising adrenaline and switching on fat-burning (catabolic) pathways in white fat, including the beta-3 adrenergic receptor. A selective knockout mouse, engineered to lose only TLQP-21 while keeping the other VGF peptides intact, is resistant to diet-induced obesity in a temperature-dependent way and activates brown fat — confirming that TLQP-21 itself has a distinct role in energy homeostasis.
How TLQP-21 works at the cell became clear with the identification of its receptor: the complement C3a receptor (C3aR1), a G-protein-coupled receptor more familiar from the immune system. Acting through C3aR1, TLQP-21 drives lipolysis in fat cells, and a study of peptide/receptor co-evolution showed that the mouse peptide binds and activates the receptor far more strongly than the human peptide does, tracing the difference to a handful of mutations in the rodent receptor's binding pocket. A separate binding partner, gC1qR, has also been reported, and in human macrophages human TLQP-21 only weakly and partially activates C3aR — raising the possibility that, in people, some of its actions use a different receptor.
Beyond fat and weight, TLQP-21 is a multifunctional peptide. It is released from pancreatic islet cells when blood glucose rises and potentiates glucose-stimulated insulin secretion. In the spinal cord it contributes to persistent pain: giving it produces hyperalgesia, and neutralising the body's own TLQP-21 reduces the hypersensitivity of inflammation and nerve injury. It also protects the stomach lining against alcohol injury and stimulates the exocrine pancreas. These varied roles mark it, like other granin peptides, as a broadly acting neuroendocrine regulator.
TLQP-21 is an endogenous VGF-derived research neuropeptide. No published study has given TLQP-21 to people as a treatment — the work is in animals and cells, including human cells in the dish — it is approved nowhere, and material sold online as 'TLQP-21' is an unregulated research chemical. Nothing here is a dose or a therapy; this page records what the published science says about the peptide.
Mechanism of Action
TLQP-21 is a 21-amino-acid peptide cut from the C-terminal region of the granin-like VGF precursor. It is a catabolic, anti-obesity neuropeptide that drives lipolysis through the complement C3a receptor (C3aR1; gC1qR also reported), potentiates glucose-stimulated insulin secretion, and contributes to spinal pain — with a marked human-versus-mouse difference in receptor potency.
VGF processing and receptors
TLQP-21 is processed from the VGF granin-like precursor and signals through the complement C3a receptor (C3aR1), with gC1qR also reported; human TLQP-21 activates C3aR far more weakly than the mouse peptide (PMIDs 31484069, 36776827).
Catabolic energy expenditure / lipolysis
Central TLQP-21 prevents diet-induced weight gain and activates fat-burning pathways (PMID 19247701); via C3aR1 it drives lipolysis in adipocytes, and its selective loss confers obesity resistance (PMIDs 31484069, 37482186).
Insulin secretion and pain
TLQP-21 is released from islets on a glucose load to potentiate insulin secretion (PMID 33348234) and contributes to inflammatory and nerve-injury pain in the spinal cord (PMID 24657450).
Published Research
These are studies of TLQP-21 read from their PubMed abstracts on November 6, 2026. They include animal studies of its prevention of diet-induced weight gain and its role in energy homeostasis (a selective knockout), its contribution to inflammatory and nerve-injury pain, and its release on a glucose load, plus cell/mechanistic studies of its lipolytic action through the complement C3a receptor and its weak partial activation of that receptor in human cells. TLQP-21 has not been given to people as a treatment; the evidence is animal and cell work.
Central TLQP-21 prevents diet-induced weight gain
Chronic intracerebroventricular TLQP-21 in fast-weight-gaining mice on a high-fat diet selectively blocked the increase in body weight and white fat despite equal overeating, normalised leptin and ghrelin, raised adrenaline, and upregulated catabolic genes in white fat (beta-3 adrenergic receptor, PPAR-delta, hormone-sensitive lipase) — supporting TLQP-21 as a catabolic neuropeptide that prevents the early phase of diet-induced obesity (a preclinical result).
TLQP-21 drives lipolysis through the C3a receptor
A structure-function and co-evolution study characterised the lipolytic mechanism of TLQP-21 through the complement C3a receptor (C3aR1) and mapped the peptide's binding motif. Mouse TLQP-21 bound and activated human C3aR1 more strongly than the human peptide and, unlike human TLQP-21, potentiated lipolysis in human adipocytes; five mutations in the rodent receptor's binding pocket accounted for the enhanced potency — relevant to developing TLQP-21-based obesity therapies (a mechanistic study).
TLQP-21 contributes to inflammatory and nerve-injury pain
In mice, spinal TLQP-21 produced dose-dependent thermal hyperalgesia (blocked by inhibitors of p38 MAP kinase, cyclooxygenase and lipoxygenase), and immunoneutralising the body's own TLQP-21 in the spinal cord reduced the tactile hypersensitivity and thermal hyperalgesia of complete-Freund-adjuvant inflammation and of spared-nerve-injury neuropathic pain — showing endogenous TLQP-21 contributes to spinal mechanisms of persistent pain (a preclinical result).
TLQP-21 is released on a glucose load
In mice, TLQP-21 immunoreactivity was present in insulin-, glucagon- and somatostatin-secreting pancreatic cells along with its receptors (C3aR1 and gC1qR). An intraperitoneal glucose load lowered pancreatic TLQP-21 at 30 minutes while raising it in plasma (peaking at 120 minutes), consistent with release of TLQP-21 from islets to enhance insulin secretion when blood glucose rises (a preclinical result).
Human TLQP-21 is a weak partial C3aR activator
In cells, TLQP-21 induced ERK signalling through human C3aR (not C5aR1 or C5aR2), but the potency of human TLQP-21 on primary human macrophages was about 135,000-fold lower than the natural ligand C3a and only reached 45% activation at the highest dose, whereas mouse TLQP-21 nearly fully activated mouse macrophages. The marked species difference suggests that in humans the actions of TLQP-21 on immune cells may not be mediated by C3aR (a cell study).
A selective TLQP-21 knockout mouse reveals its role in energy homeostasis
Using a knowledge-based point mutation of the C-terminal arginine (the pharmacophore and cleavage site), researchers created a mouse that selectively lacks TLQP-21 while keeping the other VGF peptides. These mice were grossly normal and fertile but showed a unique metabolic phenotype: a temperature-dependent resistance to diet-induced obesity and activation of brown adipose tissue — confirming a distinct, necessary role for TLQP-21 in energy homeostasis (a preclinical result).
No Established Human Dose
TLQP-21 is an endogenous VGF-derived peptide that has never been given to people as a treatment. The work is in animals and cells (including human cells in the dish), where TLQP-21 is given at experimental amounts that do not carry over to people. No regulator has approved any dose, and no published human dose exists, so no amount is printed here.
What this rests on: PMID 19247701, PMID 24657450, PMID 37482186.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes TLQP-21 is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of TLQP-21 has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store TLQP-21, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long TLQP-21 stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking TLQP-21. What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
How long it stays in the body: a half-life of not established for humans as a drug; an endogenous VGF-derived peptide. After about five half-lives almost none is left.
When effects appear: unknown; no source on this page gives a time to effect for TLQP-21. Results reported in the studies are under Published Research.
Source: half-life: PMID 31484069.
Side effects, and when to stop or get help
From the Side Effects section: No human adverse-event data exist: no published study has administered TLQP-21 to people; In animals it prevents diet-induced weight gain and drives lipolysis (PMIDs 19247701, 31484069), but it also contributes to inflammatory and nerve-injury pain (PMID 24657450) — preclinical signals, not a human safety profile; Human TLQP-21 activates its proposed receptor (C3aR) far more weakly than the mouse peptide, so animal findings may not translate (PMID 36776827); Material sold online as 'TLQP-21' is an unregulated research chemical of unverified content. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping TLQP-21. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“TLQP-21 is a research neuropeptide that has not been given to people as a drug, so there is no human safety profile; the points below reflect that research status”).
Interactions
Unknown: a PubMed search for human interaction studies of TLQP-21 (reviewed 2026-11-06) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of TLQP-21 products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a drug: Drugs@FDA and the openFDA label endpoint hold no record, and FDA GSRS and ChEMBL hold no substance record for TLQP-21 (searched November 6, 2026)). Sport: Not on the 2026 List.
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
TLQP-21 is a research neuropeptide that has not been given to people as a drug, so there is no human safety profile; the points below reflect that research status.
Contraindications & Cautions
TLQP-21 has no approved use and no label. These points reflect its research status.
Legal Status
TLQP-21 is an endogenous VGF-derived peptide studied as a research compound; it is not a drug and is not approved in any country.
Frequently Asked Questions
?What is TLQP-21?
A 21-amino-acid neuropeptide cut from the C-terminal region of the VGF precursor, a granin-like protein. It is the most studied of the VGF-derived peptides.
?What does it do?
It is a catabolic, anti-obesity peptide: given centrally it prevents diet-induced weight gain and activates fat-burning (PMID 19247701), and it drives lipolysis through the complement C3a receptor (PMID 31484069). It also potentiates insulin secretion (PMID 33348234) and contributes to pain (PMID 24657450).
?Why do mouse and human results differ?
Human TLQP-21 is a far weaker (partial) activator of its proposed receptor C3aR than the mouse peptide — about 135,000-fold less potent on human macrophages — so some of its actions in people may work through a different receptor, and animal findings may not translate directly (PMID 36776827).
?Is it approved or available to buy?
No. TLQP-21 is not a medicine, has no FDA application or label, and is approved nowhere. Material sold online as TLQP-21 is an unregulated research chemical. Grey Peptides lists no sellers and recommends no source; this page records the published science.
References
- [animal] Bartolomucci A, et al. "Chronic intracerebroventricular injection of TLQP-21 prevents high fat diet induced weight gain in fast weight-gaining mice." Genes Nutr, 2009;4(1):49-57. PMID: 19247701.
- [mechanism] Sahu BS, et al. "Peptide/Receptor Co-evolution Explains the Lipolytic Function of the Neuropeptide TLQP-21." Cell Rep, 2019;28(10):2567-2580.e6. PMID: 31484069.
- [animal] Fairbanks CA, et al. "The VGF-derived peptide TLQP-21 contributes to inflammatory and nerve injury-induced hypersensitivity." Pain, 2014;155(7):1229-1237. PMID: 24657450.
- [animal] Corda G, et al. "TLQP-21 changes in response to a glucose load." Tissue Cell, 2021;68:101471. PMID: 33348234.
- [mechanism] Li XX, et al. "TLQP-21 is a low potency partial C3aR activator on human primary macrophages." Front Immunol, 2023;14:1086673. PMID: 36776827.
- [animal] Sahu BS, et al. "Targeted and selective knockout of the TLQP-21 neuropeptide unmasks its unique role in energy homeostasis." Mol Metab, 2023;76:101781. PMID: 37482186.
- [other] UniProt O15240 (VGF neurosecretory protein, VGF gene), read November 6, 2026: TLQP-21 is a 21-amino-acid peptide processed from the C-terminal region of the VGF pro-peptide (approximately VGF residues 556-576); VGF is a granin-like protein of the regulated secretory pathway. https://www.uniprot.org/uniprotkb/O15240/entry
- [other] TLQP-21 was identified among the peptides generated from the VGF precursor and named from its N-terminal residues; its catabolic/anti-obesity, lipolytic, insulin-secretory and pain-related actions, and its signalling through the complement C3a receptor (C3aR1) and gC1qR, are from the studies carded on this page (read November 6, 2026).
- [other] US FDA, Drugs@FDA and the drug label endpoint (openFDA), searched November 6, 2026: no application and no label record for TLQP-21. It is an endogenous VGF-derived peptide, not a registered drug; FDA GSRS and ChEMBL hold no substance record for it.
Sources & Citations
The six studies carded above were read from their PubMed records on November 6, 2026. Identity comes from UniProt (O15240, VGF): TLQP-21 is a 21-residue peptide from the C-terminal region of the VGF precursor. Its catabolic/anti-obesity action, its lipolysis through the complement C3a receptor (and the human-versus-mouse potency difference), its potentiation of glucose-stimulated insulin secretion, its contribution to spinal pain, and the selective-knockout energy-homeostasis phenotype are from the studies carded on this page; the absence of US approval and of a drug substance record from Drugs@FDA, openFDA, FDA GSRS and ChEMBL was checked the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.