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Adp3.2

Adipotide (FTPP) – Forschung

Überwiegend Mechanismus / Beobachtung

5 begutachtete Studien

Was die Evidenz sagt

Überwiegend Mechanismus / Beobachtung

Die meisten Studien zu Adipotide (FTPP) sind mechanistisch oder beobachtend statt RCTs, die einen klinischen Effekt messen — betrachte die Ergebnisse als vorläufig.

Die meiste Evidenz stammt aus gemischt-qualitativen Studien, veröffentlicht 2004–2013.

Basierend auf 5 Studien

Konfidenz

Geringe Konfidenz

Nach Outcome

Weight & fat loss (preclinical)Rascher Fettabbau bei Mäusen und Affen durch Apoptose der Fettgewebe-Gefäße, jedoch keinerlei Humandaten und dosislimitierende Nierentoxizität bei Affen. · Nicht etabliert (keine Humandaten)
Überwiegend Mechanismus / Beobachtung5 Studien
Glucose & insulin resistance (preclinical)
Zu wenige bewertete Studien2 Studien
Safety profile
Zu wenige bewertete Studien2 Studien
Kidney toxicity (dose-limiting)
Zu wenige bewertete Studien1 Studie

Ältere Forschungsbasis

Neueste Studie von 2013

20042013

1Tierstudie2004

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

2Tierstudie2011

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

Quelle ansehen

3Tierstudie2012

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

Quelle ansehen

4Tierstudie2013

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

Quelle ansehen

5Übersicht2011

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

Quelle ansehen

In der Forschungsbibliothek ansehen

Adipotide (FTPP) – Forschung

Überwiegend Mechanismus / Beobachtung

Reversal of obesity by targeted ablation of adipose tissue.

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

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

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

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