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Macronutrient diet intake of the lethal yellow agouti (Ay/a) mouse
F H Koegler1, A O Schaffhauser, R L Mynatt
1Pennington Biomedical Research Center, Louisiana State University, Baton Rouge 70808, USA.
Abstract:
To examine the effect of chronic endogenous melanocortin receptor (MC-R) antagonism on macronutrient diet selection, Ay/a mice that ectopically overexpress the MC-R antagonist, agouti, were fed a three-choice macronutrient diet of pure fat, carbohydrate, and protein. Ay/a mice gained more weight and consumed a greater proportion of their daily intake from fat and less from carbohydrate than wild-type littermates did. The increased fat preference was present immediately, and persisted throughout the 7-week long experiment. Protein intake was greater for Ay/a mice; however, the proportion of protein intake to total intake was similar between mouse types. Ovarian fat pads of Ay/a mice comprised a greater percentage of total body weight that that from wild-type littermates. These results suggest that endogenous inhibition of MC-Rs mediate the increased fat intake in growing mice.
Insights
Mice with blocked melanocortin receptors (MC-Rs) showed increased weight gain and a preference for high-fat diets. This suggests MC-R inhibition drives increased fat consumption in developing mice.
Area of Science:
- Endocrinology
- Nutritional Neuroscience
- Obesity Research
Background:
- Melanocortin receptors (MC-Rs) play a crucial role in regulating energy homeostasis and appetite.
- Agouti protein is a known endogenous antagonist of MC-Rs, influencing coat color and metabolic functions.
Purpose of the Study:
- To investigate the impact of chronic endogenous melanocortin receptor (MC-R) antagonism on macronutrient diet selection in mice.
- To determine if MC-R inhibition influences weight gain and specific macronutrient preferences.
Main Methods:
- Ay/a mice, genetically modified to overexpress the MC-R antagonist agouti, were used.
- Mice were provided a three-choice diet consisting of pure fat, carbohydrate, and protein for 7 weeks.
- Body weight, daily food intake, and macronutrient selection were monitored and compared to wild-type littermates.
Main Results:
- Ay/a mice exhibited significantly greater weight gain compared to wild-type littermates.
- A clear preference for fat and reduced carbohydrate consumption was observed in Ay/a mice throughout the experiment.
- While total protein intake was higher in Ay/a mice, its proportion relative to total intake remained similar.
Conclusions:
- Endogenous inhibition of MC-Rs, mediated by agouti overexpression, directly promotes increased fat intake in growing mice.
- These findings highlight the critical role of the melanocortin system in regulating dietary fat preference and body weight regulation.