Abstract & Overview
Adipotide, also known as FTPP (Fat‑Targeted Proapoptotic Peptide), is a synthetic bifunctional peptide designed to selectively target the blood vessels that supply white adipose tissue. It operates through a dual‑domain structure that recognizes prohibitin (PHB) and annexin A2 (ANX2) expressed on adipose vasculature, initiating mitochondrial apoptosis within endothelial cells. By disrupting adipose‑specific vasculature, Adipotide reduces local blood flow to adipocytes, leading to apoptosis and resorption of fat tissue. This compound has been widely used in research exploring adipose remodeling, vascular targeting, and metabolic reprogramming mechanisms.
Molecular Pharmacology
Adipotide’s design integrates a targeting sequence and an effector sequence connected by a glycine‑glycine linker. Its structure, CKGGRAKDC‑GG‑D[KLAKLAK]₂, enables tissue specificity and mitochondrial disruption in targeted cells. The N‑terminal CKGGRAKDC motif binds to prohibitin and annexin A2 on adipose endothelial cells, while the C‑terminal D[KLAKLAK]₂ motif penetrates mitochondria, causing membrane depolarization and apoptosis. This dual‑action architecture distinguishes Adipotide from non‑specific apoptotic peptides by providing precise localization and reduced systemic toxicity in experimental models.
Mechanism of Action
The pharmacodynamic activity of Adipotide begins with its selective binding to prohibitin‑rich adipose vasculature. Following receptor engagement, the mitochondrial‑disrupting domain translocates into endothelial cells, compromising mitochondrial membrane potential and inducing caspase‑dependent apoptosis. This process leads to vascular rarefaction—reducing adipose tissue perfusion—and subsequent adipocyte atrophy and apoptosis. The result is a decrease in total white adipose mass accompanied by improved systemic metabolic parameters, including enhanced insulin sensitivity and lipid oxidation.
Metabolic and Endocrine Research Findings
In non‑human primate studies, Adipotide has demonstrated significant reductions in body fat percentage and improvements in glucose homeostasis without stimulating β‑adrenergic receptors. This mechanism differentiates it from traditional lipolytic agents by avoiding central nervous system activation. Research also indicates normalization of fasting insulin, reduced hepatic lipid accumulation, and improved AMPK‑related signaling in adipose and skeletal muscle tissues. These findings position Adipotide as an experimental model for dissecting adipose‑vascular‑metabolic interactions in obesity and metabolic syndrome.
Mitochondrial Pathway and Cellular Remodeling
Adipotide’s downstream effects are mediated through mitochondrial depolarization, release of cytochrome c, and activation of caspase‑3 and ‑9. This pathway results in targeted apoptosis and subsequent tissue remodeling via macrophage‑driven clearance of apoptotic adipocytes. Furthermore, Adipotide alters local oxidative stress balance, transiently increasing reactive oxygen species (ROS) to activate adaptive mitochondrial biogenesis in non‑adipose tissues. These combined effects contribute to improved metabolic flexibility and cellular adaptation under energy‑restricted conditions.
Comparative Mechanistic Insights
Compared to other fat‑modulating compounds such as AOD‑9604 and 5‑Amino‑1MQ, Adipotide exerts its effects through vascular apoptosis rather than hormone receptor or enzyme modulation. Where AOD‑9604 enhances lipolysis and 5‑Amino‑1MQ modulates NAD⁺ metabolism, Adipotide focuses on angiogenesis inhibition and mitochondrial disruption. This unique approach provides a complementary research model for studying energy balance, adipose signaling, and vascular integrity in metabolic disease pathways.
Summary
Adipotide represents a novel vascular‑targeted research compound that integrates tissue selectivity with mitochondrial‑mediated apoptosis. Its targeted mechanism allows researchers to explore the relationships between adipose vasculature, energy metabolism, and cellular remodeling. As studies expand into mitochondrial and angiogenic signaling, Adipotide continues to serve as a foundational tool in understanding metabolic adaptation and fat mass regulation at the molecular level.
Educational & Research Disclaimer
This article is for educational and scientific research purposes only. No therapeutic claims or usage recommendations are provided. Compounds referenced are not approved for human use and are intended solely for controlled laboratory experimentation.
Adipotide is a synthetic bifunctional research peptide designed to selectively target adipose tissue vasculature. It combines a prohibitin-binding motif with a mitochondrial-disrupting sequence to study adipose-specific vascular and metabolic mechanisms.
Adipotide binds to prohibitin (PHB) and annexin A2, proteins enriched on endothelial cells of adipose tissue vasculature. This targeting enables localized mitochondrial disruption within adipose-associated blood vessels.
Once bound to adipose vasculature, Adipotide’s effector domain induces mitochondrial membrane destabilization, triggering apoptosis in targeted endothelial cells. This mechanism is used in research to study adipose tissue remodeling and vascular dependency.
Adipotide is primarily studied in:
Adipose tissue biology
Angiogenesis inhibition mechanisms
Mitochondrial apoptosis pathways
Metabolic remodeling and fat vasculature targeting
It is used as a tool compound for mechanistic and pathway research.
No. Adipotide is not a hormone and does not directly regulate endocrine signaling. Its effects in research models are mediated through vascular targeting and mitochondrial apoptosis, not hormonal modulation.
No. Adipotide has been evaluated in experimental and early clinical research contexts but is not approved for therapeutic or clinical use. Current interest remains within laboratory and translational research.
Mazdutide : Dual GLP‑1 and Glucagon Receptor Activation in Metabolic and Lipid Regulation Research
AICAR : AMPK Activation, Cellular Energy Sensing, and Exercise‑Mimetic Signaling in Research Models
Apelin : APJ Receptor Signaling, Cardiovascular Regulation, and Metabolic Research Pathways
