Adipotide

Adipotide does not aim at the fat cell itself but at its supply line: the peptide, listed in the literature as Prohibitin-TP01 or as FTPP, short for Fat-Targeted Pro-apoptotic Peptide, homes in on the blood vessels that run through white adipose tissue.

How the molecule is built:

• 21 amino acids with a defined fold, as a conjugate of two functional parts.
• Part one recognizes prohibitin, a protein found in the vessel lining of white fat, and docks there.
• Part two carries a pro-apoptotic sequence that starts programmed cell death in the target cell.

What follows from that in preclinical studies: the endothelial cells of the fat tissue's microvessels are hit selectively, the metabolic supply of the tissue drops, and over several weeks adipocyte volume changes. Much of this work comes from the Arap and Pasqualini laboratory at MD Anderson Cancer Center.

Findings from the animal models:

• Obese Old World monkeys: targeted apoptosis in the vessels of white fat, rapid weight loss, better insulin resistance, plus predictable and reversible changes in renal tubule function.
• Rodents (mice and rats) fed a high-fat diet: lower body weight through reduced food intake at unchanged energy expenditure, with no sign of sickness in a taste aversion test.
• Obese mice: better glucose tolerance within two to three days, regardless of weight or food intake, alongside lower insulin and triglyceride levels.

Mechanistically, adipotide thus stands apart from GLP-1 and mitochondrial approaches; for an experimental tool the data are considerable, but they include safety concerns at higher doses.

Adipotide is an experimental tool with an unusually targeted mechanism acting on vessels; unlike the mild lipotropic blends, earlier investigations explicitly raised safety concerns at higher doses.

• Kidney: in the primate studies, higher doses produced reversible effects on kidney function, which clearly sets adipotide apart from the mild substances in this area.
• Dose: the safety profile worsens in the literature as the dose rises, and the data argue for narrow dose windows.
• Injection site: mild redness, pressure or brief irritation is documented.
• Human data: there are no robust human studies; what exists comes from rodents and primates, and those models produced safety signals.

This summary is no substitute for medical advice.

• Reversal of obesity by targeted ablation of adipose tissue - the first description from 2004.
• A peptidomimetic targeting white fat in obese monkeys - the primate study with weight loss, insulin resistance and the reversible kidney findings.
• Peptide eliciting apoptosis in adipose tissue endothelium reduces food intake and body weight - the rodent study on a high-fat diet, taste aversion test included.
• Weight-independent improvement of glucose tolerance by an adipose endothelium-targeting peptide - the mouse study on glucose tolerance within a few days.