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Mixed-Chirality Prohibitin Peptide: D-(RLARLAR)2 Enhances Stability and In Vivo Effects on Obesity
Lai Yue Chan1, Benjamin D Weger2, Meltem Weger2
1Institute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, Queensland 4072, Australia.
Journal of the American Chemical Society
|July 1, 2025
Summary
New prohibitin peptides target white adipose tissue to reduce body weight and adipocyte expansion. This obesity treatment approach induces mitochondrial uncoupling, showing promise for metabolic syndrome therapies.
Area of Science:
- Biochemistry
- Metabolic Science
- Pharmacology
Background:
- Obesity is a global epidemic and a major risk factor for type 2 diabetes.
- Pharmacotherapies offer a supplementary approach to lifestyle changes for sustained weight loss.
Purpose of the Study:
- To design and engineer a new generation of prohibitin peptide-based therapeutics targeting white adipose tissues.
- To evaluate the efficacy of these novel peptides in reducing body weight and adipocyte expansion.
Main Methods:
- Development of prohibitin peptide-based therapeutics.
- Administration of peptides in a high-fat diet-induced obesity mouse model.
- Assessment of body weight reduction and adipocyte function.
Main Results:
- Engineered prohibitin peptides significantly reduced body weight in an obesity mouse model.
- The compound PTP-r (prohibitin-TP01 substituted with d-arginine) demonstrated potent efficacy.
- The treatment induced mitochondrial uncoupling in adipose tissue.
Conclusions:
- Next-generation adipose-targeting prohibitin peptides show promise for obesity treatment.
- These peptides effectively curb adipocyte expansion and body weight.
- Favorable preclinical safety profiles suggest potential for treating obesity and metabolic syndrome.
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