Adipotide
Also known as: CKGGRAKDC-GG-(D)(KLAKLAK)2, proapoptotic peptide (PP), peptidomimetic adipotide
Peptidomimetic / Pro-apoptotic vascular-targeting peptide
What it is
Adipotide (CKGGRAKDC-GG-(D)(KLAKLAK)2) is a ligand-directed peptidomimetic that targets prohibitin, a vascular marker expressed on the endothelium of white adipose tissue (WAT). Upon binding, it induces targeted apoptosis within blood vessels surrounding white adipose tissue, leading to reductions in WAT mass. A comparative study also demonstrated that the pro-apoptotic peptide component [(D)(KLAKLAK)2, KLA] delivered via prohibitin-targeted nanoparticles achieves similar adipose vascular targeting, suggesting prohibitin engagement is key to adipose tissue selectivity. In obese mice, the peptide rapidly and potently improved glucose tolerance in a weight- and food intake-independent manner, with associated decreases in serum insulin and triglycerides; microarray analysis revealed reversal of HFD-induced changes in mitochondrial dysfunction, oxidative phosphorylation, and branched-chain amino acid degradation pathways in adipose tissue. A comment on the primary primate study raised the alternative hypothesis that observed weight loss may partly reflect a direct effect of adipotide on food consumption rather than solely apoptosis of adipose vasculature.
Class: Peptidomimetic / Pro-apoptotic vascular-targeting peptide
What it's studied for
- Obesity treatment / weight loss Mixed
- Treatment of obese Old World monkeys with adipotide induced targeted apoptosis in white adipose tissue vasculature, resulting in rapid weight loss confirmed by MRI and DXA. Reversible renal proximal tubule function changes were observed at experimentally determined optimal doses across three primate species. PMID 22072637 Barnhart KF et al. Science Translational Medicine (2011)
- In diet-induced obese (DIO) mice, systemic injection of prohibitin-targeted nanoparticles encapsulating KLA (the pro-apoptotic component of adipotide) reduced body weight and serum leptin levels. Adipotide bioconjugate was used as a comparator; KLA-PTNP outperformed bioconjugate on several metabolic endpoints at a lowe PMID 23871959 Hossen N et al. Journal of Controlled Release (2013)
- Commentary proposing that weight loss observed in obese monkeys treated with adipotide may reflect a direct effect on food consumption rather than solely adipose vascular apoptosis. PMID 22539771 Criscione L. Science Translational Medicine (2012)
- Improvement of insulin resistance / glucose tolerance Mixed
- Adipotide treatment in obese primates improved insulin resistance alongside weight loss and reduction in white adipose tissue volume. PMID 22072637 Barnhart KF et al. Science Translational Medicine (2011)
- In obese high-fat-diet mice, the pro-apoptotic peptide rapidly and potently improved glucose tolerance within 2–3 days of treatment, independent of changes in body weight or food intake. Serum insulin and triglycerides were decreased. Microarray analysis showed reversal of HFD-induced mitochondrial and metabolic pathwa PMID 22733798 Kim DH et al. Diabetes (2012)
- Reduction of white adipose tissue / dysfunctional adipose tissue Animal studies only
- The pro-apoptotic peptide targeting WAT endothelium reduced adiposity and altered serum fatty acid and acylcarnitine profiles in obese mice on a high-fat diet. PMID 22733798 Kim DH et al. Diabetes (2012)
- KLA-PTNP (comparator to adipotide bioconjugate) reduced ectopic fat deposition in liver and muscle and elevated serum adiponectin with lipolytic action in DIO C57BL/6 mice, with no detectable hepatotoxicity. PMID 23871959 Hossen N et al. Journal of Controlled Release (2013)
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| Not specified in abstract | Experimentally determined optimal doses (specific numerical dose not stated in abstract) | Not specified in abstract | animal | Research PMID 22072637 |
| Not specified in abstract | Not specified numerically in abstract | Treatment assessed at days 2 and 3 | animal | Research PMID 22733798 |
| Systemic injection | Low dose (specific numerical dose not stated in abstract) of KLA-PTNP; adipotide bioconjugate used as comparator | Not specified in abstract | animal | Research PMID 23871959 |
Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.
Safety signals
- Reversible renal proximal tubule function changes observed in obese monkeys from three different species at experimentally determined optimal doses of adipotide. PMID 22072637
- Possible effect on food consumption in treated primates, complicating interpretation of weight loss as purely mechanism-driven (i.e., adipose vascular apoptosis vs. appetite suppression). PMID 22539771
Contraindications
- No explicit contraindications stated in the reviewed literature. Renal impairment may represent a concern given observed proximal tubule function changes in primate studies, but this is not explicitly stated as a contraindication in any abstract. PMID 22072637
Frequently asked
What is adipotide and how does it work?
Adipotide (CKGGRAKDC-GG-(D)(KLAKLAK)2) is a ligand-directed peptidomimetic that targets prohibitin on the endothelium of white adipose tissue blood vessels and induces apoptosis in those vessels, reducing white adipose tissue mass. In obese primates it produced rapid weight loss and improved insulin resistance. In obese mice, it also rapidly improved glucose tolerance independently of weight or food intake changes, with reversal of HFD-induced metabolic pathway dysregulation in adipose tissue.
Has adipotide been tested in humans?
Based on the reviewed literature, adipotide has been studied in obese Old World monkeys and obese mice. No human clinical trial data are reported in the reviewed abstracts. The primate study described adipotide as 'a prototype in a new class of candidate drugs that may be useful for treating obesity in humans', but this does not confirm human trials have been conducted.
What dose of adipotide should I take?
I'm not a medical professional and can't recommend a protocol for you specifically. What research has shown: all available dosing information comes from animal studies (non-human primates and mice), and the reviewed abstracts do not report specific numerical doses — only 'experimentally determined optimal doses' in primates and unspecified doses in mice. No human dosing data exist in the reviewed literature.
Is adipotide safe?
The reviewed literature identified one notable safety signal: reversible renal proximal tubule function changes in obese monkeys across three species treated with adipotide at experimentally determined optimal doses. A commentary also raised uncertainty about whether weight loss reflects adipose vascular apoptosis or a direct effect on food consumption. No human safety data are available in the reviewed abstracts. Please consult a licensed healthcare provider before considering use of any experimental compound.
Does adipotide affect the kidneys?
Yes — the primate study reported predictable and reversible changes in renal proximal tubule function at experimentally determined optimal doses, observed across three different monkey species. The abstract describes these changes as reversible, but no long-term renal follow-up data or human kidney safety data are available in the reviewed literature.
Can adipotide improve insulin resistance or blood sugar?
In obese primates, adipotide treatment was associated with improved insulin resistance alongside weight loss. In obese mice, the pro-apoptotic peptide rapidly and potently improved glucose tolerance within 2–3 days, independently of body weight or food intake changes, with decreases in serum insulin and triglycerides. These findings are from animal studies only; no human data are available in the reviewed literature.
Can I stack adipotide with other peptides or weight loss drugs?
I can't recommend combining compounds — that's a prescribing decision. Here's what has been studied individually: adipotide has been studied alone in obese monkeys and mice. No combination or stacking studies are reported in the reviewed abstracts.
Where can I buy adipotide?
I don't recommend vendors or sources. Please consult a licensed provider.
How is adipotide different from semaglutide or other GLP-1 drugs?
I don't have reliable study data on that specific question. I won't guess — please consult a licensed provider or peer-reviewed literature directly. What the reviewed abstracts do state is that adipotide works by inducing apoptosis in white adipose tissue blood vessels via prohibitin targeting, a mechanism distinct from GLP-1 receptor agonism; however, no head-to-head comparison studies are included in the reviewed literature.
Can adipotide be used to treat a medical condition I have?
I can't suggest treatments for medical conditions. Please speak with a licensed healthcare provider. For context, adipotide has only been studied in animal models (non-human primates and mice) in the reviewed literature, and no human clinical data are available.
References
- [1] PMID 22072637 — Treatment of obese Old World monkeys with adipotide induced targeted apoptosis in white adipose tissue vasculature, resulting in rapid weight loss confirmed by
- [2] PMID 23871959 — In diet-induced obese (DIO) mice, systemic injection of prohibitin-targeted nanoparticles encapsulating KLA (the pro-apoptotic component of adipotide) reduced b
- [3] PMID 22539771 — Commentary proposing that weight loss observed in obese monkeys treated with adipotide may reflect a direct effect on food consumption rather than solely adipos
- [4] PMID 22733798 — In obese high-fat-diet mice, the pro-apoptotic peptide rapidly and potently improved glucose tolerance within 2–3 days of treatment, independent of changes in b