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Adp3.2

Adipotide (FTPP) Research

Mostly mechanism / observational

5 peer-reviewed studies

What the evidence says

Mostly mechanism / observational

Most Adipotide (FTPP) studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.

Most evidence is from mixed-quality studies published 2004–2013.

Based on 5 studies

Confidence

Low confidence

By outcome

Weight & fat loss (preclinical)Rapid fat loss in mice and monkeys via fat-vasculature apoptosis, but no human data of any kind and dose-limiting kidney toxicity in monkeys. · Not established (no human data)
Mostly mechanism / observational5 studies
Glucose & insulin resistance (preclinical)
Too few graded studies2 studies
Safety profile
Too few graded studies2 studies
Kidney toxicity (dose-limiting)
Too few graded studies1 study

Older research base

Newest study from 2013

20042013

1Animal2011

In plain English: Treatment with adipotide induced targeted apoptosis within blood vessels of white adipose tissue and resulted in rapid weight loss and improved insulin resistance in obese monkeys ... monkeys from three different species displayed predictable and reversible changes in renal proximal tubule function.

Barnhart KF, Christianson DR, Hanley PW, Driessen WH, Bernacky BJ, Baze WB, et al. · Sci Transl Med (2011)

The pivotal translation step: the ligand-directed peptidomimetic CKGGRAKDC-GG-(D)(KLAKLAK)2 ('adipotide') tested in obese Old World monkeys
Induced targeted apoptosis in white-fat blood vessels with rapid weight loss and improved insulin resistance, confirmed by MRI and DXA
MANDATORY COUNTER-EVIDENCE: at effective doses, monkeys of three species showed predictable, reversible changes in renal proximal-tubule function — the dose-limiting toxicity

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2Animal2004

In plain English: Targeting a proapoptotic peptide to prohibitin in the adipose vasculature caused ablation of white fat. Resorption of established white adipose tissue and normalization of metabolism resulted in rapid obesity reversal without detectable adverse effects.

Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W. · Nat Med (2004)

Foundational proof-of-concept: in vivo phage display isolated the CKGGRAKDC peptide that homes to white-fat vasculature and binds prohibitin
Fusing a proapoptotic peptide to that homing motif ablated white adipose tissue in obese mice
Resorption of established white fat normalized metabolism and rapidly reversed obesity

3Animal2012

In plain English: PP rapidly and potently improved glucose tolerance of obese mice in a weight- and food intake-independent manner.

Kim DH, Sartor MA, Bain JR, Sandoval D, Stevens RD, Medvedovic M, et al. · Diabetes (2012)

Treated obese high-fat-diet mice with the same proapoptotic peptide that ablates white-adipose-tissue endothelium
Glucose tolerance improved rapidly and potently, independent of weight loss and food intake
Serum insulin and triglycerides fell; fatty-acid and acylcarnitine profiles shifted relative to vehicle and pair-fed controls

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4Review2011

In plain English: Approaches in which the mature WAT vasculature is disrupted have been sought with the aim of combating obesity after its onset ... This review discusses recent advances in WAT vascular targeting and implications for the development of new anti-obesity therapeutics.

Daquinag AC, Zhang Y, Kolonin MG. · Trends Pharmacol Sci (2011)

Review from the Kolonin lab framing the vascular-targeting anti-obesity strategy that adipotide embodies
Explains that white-adipose-tissue expansion depends on angiogenesis, so disrupting or ablating the mature WAT vasculature can combat established obesity
Discusses adipose stromal cells and other WAT vascular targets as candidates for combinatorial treatment

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5Animal2013

In plain English: The systemic injection of DIO mice with a low dose of KLA-PTNP, rather than a bioconjugate composed of the same targeting peptide and KLA (Adipotide) resulted in a reduction in body weight.

Hossen MN, Kajimoto K, Akita H, Hyodo M, Harashima H. · J Control Release (2013)

Compared a prohibitin-targeted nanoparticle carrying the KLA proapoptotic peptide against the adipotide bioconjugate itself in diet-induced-obese mice
Both target the same prohibitin marker on adipose vasculature; the nanoparticle achieved weight reduction at a low dose with reduced serum leptin
Reported reduced ectopic fat in liver and muscle and raised adiponectin, with no detectable hepatotoxicity in the nanoparticle arm

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View in Research Library

Adipotide (FTPP) Research

Mostly mechanism / observational

A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys.

Reversal of obesity by targeted ablation of adipose tissue.

Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium.

Vascular targeting of adipose tissue as an anti-obesity approach.

A comparative study between nanoparticle-targeted therapeutics and bioconjugates as obesity medication.