Adipotide (CKGGRAKDC) is a cyclic pro-apoptotic peptide that targets white adipose tissue vasculature by binding PROHIBITIN — a mitochondrial chaperone protein expressed on the luminal surface of adipose blood vessel endothelium but not on vessels supplying other tissues. Upon PROHIBITIN binding, adipotide is internalised, disrupts mitochondrial function in adipose endothelial cells, and triggers apoptosis — causing adipose vascular regression and secondary adipocyte death. In obese rhesus macaques, adipotide produced significant fat mass reduction. It is the primary research tool for studying adipose tissue vasculature biology and targeted proapoptotic approaches to fat reduction.
Adipotide mechanism is unique — tissue targeting via receptor-mediated vascular apoptosis:
PROHIBITIN binding: CKGGRAKDC binds PROHIBITIN expressed on luminal surface of white adipose blood vessel endothelium — selective due to adipose-specific surface expression pattern
Internalisation: Peptide-PROHIBITIN complex is endocytosed into vascular endothelial cells
PROHIBITIN is normally an intramitochondrial chaperone. In adipose vascular endothelium specifically, it is expressed on the cell surface — accessible to circulating peptides. This aberrant surface expression pattern (not found on muscle, cardiac, or hepatic vasculature) gives adipotide its fat selectivity. Understanding what drives this selective surface expression is an open research question.
Key Research Studies & Data
Study
Model
Finding
Kolonin et al. 2004 (Nat Med)
DIO mouse model — adipotide IP
Selective fat mass reduction; adipose vascular regression confirmed by IHC; liver/muscle/heart unaffected
Bhatt et al. 2011 (Sci Trans Med)
Obese rhesus macaques — adipotide SC daily × 28 days
Flow cytometry: anti-PROHIBITIN in non-permeabilised primary endothelial cells from adipose, muscle, cardiac, hepatic, and pulmonary tissue. Confocal IF — cell surface PROHIBITIN. Defines tissue selectivity basis.
Protocol 3: Vascular apoptosis mechanism
Adipotide 1-10 µM in primary adipose vs muscle endothelial cells. TUNEL/Annexin V/PI flow (24hr), caspase-3 activity, JC-1 mitochondrial membrane potential, cytochrome c release (WB). Confirm selectivity in cell-based assay.
Protocol 4: NHP-equivalent dose finding
Dose escalation 0.5-8 mg/kg SC × 7 days in DIO rats. Body weight, organ weights, plasma metabolic panel (ALT/AST/BUN/creatinine/LDH), adipose IHC (CD31/TUNEL). Safety window characterisation.
❓
Frequently Asked Questions
What is adipotide?
Adipotide is a cyclic pro-apoptotic peptide (CKGGRAKDC) that selectively targets white adipose tissue vasculature by binding PROHIBITIN on adipose endothelial cell surfaces, triggering vascular apoptosis → adipose vascular regression → fat mass reduction.
Why is adipotide selective for fat tissue?
PROHIBITIN is normally intramitochondrial but is expressed on the cell surface specifically in white adipose vascular endothelium — not found on muscle, cardiac, or hepatic vessel endothelium. This selective surface expression gives adipotide its tissue targeting.
What did the rhesus macaque study show?
Bhatt et al. 2011 (Sci Trans Med) showed adipotide SC daily for 28 days in obese macaques reduced body weight 11% and visceral fat 39%, with improved insulin sensitivity. High-dose renal toxicity resolved on cessation.
How does adipotide differ from GLP-1R agonists for fat reduction?
GLP-1R agonists reduce fat via CNS appetite suppression and metabolic effects. Adipotide acts directly on adipose vasculature via apoptosis — no receptor in the GLP-1/GIP/GCGR axis. They can be combined to study complementary fat reduction mechanisms.
What formats does QSC supply adipotide in?
QSC supplies adipotide as lyophilised research vials, ≥99% purity HPLC verified with Janoshik COA. Ships from domestic warehouses in USA, EU, UK, Canada, and Australia.
