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Intermittent MTII application evokes repeated anorexia and robust fat and weight loss
Yi Zhang1, Renata Collazo, Yongxin Gao
1Research Department, Malcom Randall Veterans Affairs Medical Center-NF/SG HSC, Rm E585-1, 1601 SW Archer Road, Gainesville, FL 32608, USA. yizhang@ufl.edu
Peptides
|December 26, 2009
Summary
Intermittent melanotan II (MTII) therapy preserves anorectic responses but does not prevent tachyphylaxis. Constant MTII blunts further food response, yet both methods significantly reduce weight and adiposity.
Area of Science:
- Neuroendocrinology
- Metabolic Regulation
- Pharmacology
Background:
- Central melanocortins (MC) induce potent but short-lived appetite suppression.
- Tachyphylaxis, a rapid decrease in drug effectiveness, develops within days of MC treatment.
- Melanotan II (MTII) is an MC analog with potential therapeutic applications.
Purpose of the Study:
- To investigate if intermittent melanotan II (MTII) therapy minimizes tachyphylaxis and enhances long-term efficacy.
- To compare the effects of intermittent versus continuous MTII administration on food intake and body weight.
- To explore the molecular mechanisms underlying MTII's effects on appetite and metabolism.
Main Methods:
- F344/BN rats received intracerebroventricular infusions of MTII or vehicle via mini-pump for 14 days.
- Rats were then divided into intermittent (MTII-On/Off) and continuous (MTII-On) treatment groups for 10 days.
- A final 6-day period involved fresh MTII administration in both groups, followed by assessments of food intake, body weight, gene expression, and adiposity.
Main Results:
- Initial MTII infusion caused a 30% food reduction, which attenuated within 5 days.
- Intermittent MTII re-administration elicited a robust anorectic response, while continuous MTII did not further suppress food intake.
- Both treatment regimens significantly reduced body weight and adiposity by 80%, with elevated acetyl-CoA carboxylase 1 phosphorylation in adipose tissue.
Conclusions:
- Intermittent MTII treatment preserves anorectic responses but does not overcome tachyphylaxis.
- Continuous MTII administration blunts further appetite suppression after initial tachyphylaxis.
- Both intermittent and continuous MTII lead to substantial weight and fat reduction, potentially via enhanced fatty acid oxidation.
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