title: Activation of the central melanocortin system chronically reduces body mass without the necessity of long-term caloric restriction.
abstract: Melanotan II (MTII) is a potent appetite suppressor that rapidly reduces body mass. Given the rapid loss of anorexic response upon chronic MTII treatment, most investigations have focused on the initial physiological adaptations. However, other evidence supports MTII as a long-term modulator of energy balance that remains to be established. Therefore, we examined the chronic effects of MTII on energy homeostasis. MTII (high or low dose) or artificial cerebrospinal fluid (aCSF) was infused into the lateral ventricle of the brain of 6-month-old F344BN rats (6-7/group) over 40 days. MTII suppressed appetite in a dose-dependent manner (P < 0.05). Although food intake promptly rose back to control level, body mass was persistently reduced in both MTII groups (P < 0.01). At day 40, both MTII groups displayed lower adiposity than the aCSF animals (P < 0.01). These results show that MTII chronically reduces body mass without the requirement of long-term caloric restriction. Our study proposes that food restriction helps initiate mass loss; however, combined with a secondary pharmacological approach preserving a negative energy balance state over time may help combat obesity.
authors.affiliation: a Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA.
authors.forename: I
authors.initials: I
authors.lastname: Côté
authors.affiliation: a Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA.|b Geriatric Research, Education, and Clinical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Sakarya
authors.affiliation: a Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA.|b Geriatric Research, Education, and Clinical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, USA.
authors.forename: N
authors.initials: N
authors.lastname: Kirichenko
authors.affiliation: c Department of Psychiatry, University of Florida, Gainesville, FL, USA.
authors.forename: D
authors.initials: D
authors.lastname: Morgan
authors.affiliation: d Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Carter
authors.affiliation: a Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA.|b Geriatric Research, Education, and Clinical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, USA.
authors.forename: N
authors.initials: N
authors.lastname: Tümer
authors.affiliation: a Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Scarpace
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D031204:Caloric Restriction; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D018737:Hand Strength; D057967:Infusions, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D010456:Peptides, Cyclic; C079282:melanotan-II; D000521:alpha-MSH
keywords: MTII; apport alimentaire; body mass; central melanocortin system; food intake; lean body mass; masse corporelle; masse corporelle maigre; système de la mélanocortine central