Melanocortin activity in the amygdala controls appetite for dietary fat.
The amygdala is rich in melanocortin 4 receptors. Because the reduction in dietary fat intake after enterostatin is injected in the central nucleus of the amygdala (CeA) is blocked by a melanocortin 4 receptor antagonist, we investigated the role of melanocortin activity in the CeA in regulating food intake and macronutrient choice. Sprague-Dawley rats, fitted with CeA cannulas, were fed either chow, a high-fat (HF) diet, or adapted to a two-choice HF or low-fat (LF) diet. Injections of the MC4R agonist melanotan II (MTII) in the CeA had a dose-dependent inhibitory effect on food intake that lasted for at least 24 h. This response was greater in rats fed a HF diet. The inverse agonist agouti-related protein (AgRP) and antagonist SHU-9119 increased food intake in a dose-dependent manner, with the hyperphagia lasting for 60 h. In rats adapted to a two-choice HF/LF diet, MTII decreased HF consumption but had no effect on LF consumption, resulting in a long-lasting decrease in total calorie intake (-35.5% after 24 h, P < 0.05). Total calorie intake increased in both AgRP- and SHU-9119-treated rats (32 and 109% after 24 h, respectively) as the result of increased intake of HF diet. There was no modification of LF consumption with AgRP treatment and a transient nonsignificant decrease with SHU-9119 treatment. Amygdala brain-derived neurotrophic factor expression was increased by AgRP in fed rats. These results identify the amygdala as a site of action for the melanocortin system to control food intake and dietary preferences.
Boghossian
Stéphane
S
Center for Advanced Nutrition, Utah State Univ., 4715 Old Main Hill, Logan, UT 84322, USA.
Park
MieJung
M
York
David A
DA
D054369:Agouti-Related Protein / Q000494:pharmacology; D000679:Amygdala / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001069:Appetite Regulation / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D004041:Dietary Fats; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005518:Food Preferences / Q000187:drug effects; D008297:Male; D053486:Melanocortins / Q000494:pharmacology / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044101:Receptors, Melanocortin / Q000819:agonists / Q000037:antagonists & inhibitors; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000494:pharmacology
D054369:Agouti-Related Protein; D019208:Brain-Derived Neurotrophic Factor; D004041:Dietary Fats; D053486:Melanocortins; D010456:Peptides, Cyclic; D044101:Receptors, Melanocortin; C079282:melanotan-II; D000521:alpha-MSH