Inhibitory Effect of the Melanocortin Receptor Agonist Melanotan-II (MTII) on Feeding Depends on Dietary Fat Content and not Obesity in Rats on Free-Choice Diets.

van den Heuvel JK, Eggels L, van Rozen AJ, Fliers E, Kalsbeek A, Adan RA, la Fleur SE

Frontiers in behavioral neuroscience24 Dec 2015Cited by 2 (Europe PMC)

PMID26733840PMCIDPMC4689860DOI10.3389/fnbeh.2015.00358PepBankPUB-26733840

Summary

IntroductionConflicting data exist on sensitivity changes of the melanocortin system during diet-induced obesity. We hypothesized that melanocortin sensitivity depends on diet composition, in particular on the fat content rather than the level of obesity. The aim of this study was to determine the influence of diet composition on feeding responses to a melanocortin receptor agonist, using free-choice diets that differ in food components.MethodsMale Wistar rats were subjected to a chow (CHOW) diet or a free-choice (fc) diet of either chow, saturated fat and liquid sugar (fcHFHS), chow and saturated fat (fcHF), or chow and liquid sugar (fcHS) for 4 weeks. Melanocortin sensitivity was tested by measuring food intake following administration of the melanocortin 3/4 receptor agonist melanotan II (MTII) or vehicle in the lateral ventricle. In a separate experiment, proopiomelanocortin (POMC) and agouti-related protein (AgRP) mRNA levels were determined in the arcuate nucleus with in situ hybridization in rats subjected to the free-choice diets for 4 weeks.ResultsRats on the fcHFHS diet for 4 weeks show increased caloric intake and body weight gain compared to rats on the CHOW, fcHS and fcHF diet. Caloric intake and body weight gain was comparable between rats on the fcHF, fcHS, and CHOW diet. After 4 weeks diet, POMC and AgRP mRNA levels were not different between diet groups. MTII inhibited caloric intake to a larger extent in rats on the fcHF diet compared to rats on the CHOW, fcHFHS or fcHS diet. Moreover, the fat component was the most inhibited by MTII, and the sugar component the least.ConclusionRats on the fcHF diet show stronger food intake inhibition to the melanocortin receptor agonist MTII than rats on the CHOW, fcHS, and fcHFHS diet, which is independent of caloric intake and body weight gain. Our data point toward an important role for diet composition, particularly the dietary fat content, and not obesity in the sensitivity of the melanocortin system.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In male Wistar rats, MTII inhibited caloric intake more in rats on the free-choice fcHF diet than in rats on the chow, fcHFHS or fcHS diet.
In plain wordsIn rats, melanotan II cut calorie intake more in rats on a fat-choice diet than in rats on the other diets.
Peptide
Melanotan II
Outcome
IncreaseMTII inhibition of caloric intake on fcHF diet versus other diets
Study
ratn: not reported in source
Comparator
CHOW, fcHFHS and fcHS diet rats
Outcome group
Appetite and food intake · Metabolic and weight
Studied dose
Dose not stated · intracerebroventricular (lateral ventricle)As given in this study (rat).
Source sentences
Summary
MTII inhibited caloric intake to a larger extent in rats on the fcHF diet compared to rats on the CHOW, fcHFHS or fcHS diet.
1 context sentence(design, population, supporting numbers)
Summary · context
Male Wistar rats were subjected to a chow (CHOW) diet or a free-choice (fc) diet of either chow, saturated fat and liquid sugar (fcHFHS), chow and saturated fat (fcHF), or chow and liquid sugar (fcHS) for 4 weeks. Melanocortin sensitivity was tested by measuring food intake following administration of the melanocortin 3/4 receptor agonist melanotan II (MTII) or vehicle in the lateral ventricle.
Show in the study text Report a problemFND-2673384001
02AnimalAnimal study (in vivo)Efficacy outcome
In rats on free-choice diets, MTII inhibited intake of the fat component most and the sugar component least.
In plain wordsIn rats, melanotan II reduced intake of dietary fat the most and sugar the least.
Peptide
Melanotan II
Outcome
MixedMTII inhibition by food component
Study
ratn: not reported in source
Comparator
Other food components
Outcome group
Appetite and food intake · Metabolic and weight
Studied dose
Dose not stated · intracerebroventricular (lateral ventricle)As given in this study (rat).
Source sentences
Summary
Moreover, the fat component was the most inhibited by MTII, and the sugar component the least.
1 context sentence(design, population, supporting numbers)
Summary · context
Male Wistar rats were subjected to a chow (CHOW) diet or a free-choice (fc) diet of either chow, saturated fat and liquid sugar (fcHFHS), chow and saturated fat (fcHF), or chow and liquid sugar (fcHS) for 4 weeks. Melanocortin sensitivity was tested by measuring food intake following administration of the melanocortin 3/4 receptor agonist melanotan II (MTII) or vehicle in the lateral ventricle.
Show in the study text Report a problemFND-2673384002

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Version 2Current
10 Oct 2026, 09:43 UTC
Study results updated
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC

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