Macronutrient Diet Intake of the Lethal Yellow Agouti (Ay/a) Mouse

Koegler, Frank H.; Schaffhauser, Andrea O.; Mynatt, Randall L.; York, David A.; Bray, George A.

doi:10.1016/s0031-9384(99)00104-3

Cited by 44 publications

(32 citation statements)

References 11 publications

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“…Increased antagonism at MC4R receptors, either brought about pharmacologically by icv administration of AgRP or as a result of ectopic production of Agouti in the case of obese A y /a mice, results in a preferential consumption of fat (23,24). In contrast, administration of the potent melanocortin agonist MTII can cause a reduction in fat consumption (25).…”

Section: Pomc and Dietary Macronutrients-a Gene-environment Interactionmentioning

confidence: 99%

Pro-opiomelanocortin (POMC)-derived peptides and the regulation of energy homeostasis

Coll

Tung

2009

Molecular and Cellular Endocrinology

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Section: Pomc and Dietary Macronutrients-a Gene-environment Interactionmentioning

confidence: 99%

Pro-opiomelanocortin (POMC)-derived peptides and the regulation of energy homeostasis

Coll

Tung

2009

Molecular and Cellular Endocrinology

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“…Data also suggest that central melanocortin signaling may specifically regulate the consumption of dietary fats. The lethal yellow (A y /a) agouti mouse, in which ectopic expression of the agouti protein is presumed to block the central melanocortin-3 receptor (MC3R) and MC4R, shows a preference for fat consumption that is not seen in wild-type (WT) C57BL/6J mice on a three-choice macronutrient diet of carbohydrate, fat, or protein (7). Intracerebroventricular (ICV) administration of agouti-related protein (AgRP), an endogenous CNS antagonist of the MC3R and MC4R, preferentially increases acute consumption of high-fat chow in a two-choice paradigm providing high-fat and low-fat chow in Long-Evans rats (8).…”

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confidence: 99%

Melanocortin-4 receptor mutations paradoxically reduce preference for palatable foods

Panaro

Cone

2013

Proc. Natl. Acad. Sci. U.S.A.

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Haploinsufficiency of the melanocortin-4 receptor (MC4R) results in melanocortin obesity syndrome, the most common monogenic cause of severe early onset obesity in humans. The syndrome, which produces measurable hyperphagia, has focused attention on the role of MC4R in feeding behavior and macronutrient intake. Studies show that inhibition of MC4R signaling can acutely increase the consumption of high-fat foods. The current study examines the chronic feeding preferences of mice with deletion of one or both alleles of the MC4R to model the human syndrome. Using twochoice diet paradigms with high-fat or high-carbohydrate foods alongside normal chow, we show, paradoxically, that deletion of one allele has no effect, whereas deletion of both alleles of the MC4R actually decreases preference for palatable high-fat and high-sucrose foods, compared with wild-type mice. Nonetheless, we observed hyperphagic behavior from increased consumption of the low-fat standard chow when either heterozygous or homozygous mutant animals were presented with dietary variety. Thus, decreased MC4R signaling in melanocortin obesity syndrome consistently yields hyperphagia irrespective of the foods provided, but the hyperphagia appears driven by variety and/or novelty, rather than by a preference for high-fat or high-carbohydrate foodstuffs.food preference | food intake | reward F ood preference in humans is highly complex, involving cultural, sociological, psychological, and physiological factors. Physiological inputs to food preference include both homeostatic and hedonic drives, with the latter referring to the effects of sensory and reward pathways that control the desire to consume highly palatable energy-dense foods (1). Profound hyperphagia has been demonstrated in several of the monogenic obesity syndromes (2), and it is important to determine the mechanisms that drive hyperphagia, including the relative contributions of homeostatic versus hedonic drives and their impact on food preference.Melanocortin obesity syndrome, resulting from null or hypomorphic mutations in one allele of the melanocortin-4 receptor (MC4R), is the most common monogenic cause of severe early onset obesity in humans (3, 4). The obese phenotype is due in large part to hyperphagia, which has been documented in humans (3) and in mouse (4, 5) and rat (6) models of the syndrome. Data also suggest that central melanocortin signaling may specifically regulate the consumption of dietary fats. The lethal yellow (A y /a) agouti mouse, in which ectopic expression of the agouti protein is presumed to block the central melanocortin-3 receptor (MC3R) and MC4R, shows a preference for fat consumption that is not seen in wild-type (WT) C57BL/6J mice on a three-choice macronutrient diet of carbohydrate, fat, or protein (7). Intracerebroventricular (ICV) administration of agouti-related protein (AgRP), an endogenous CNS antagonist of the MC3R and MC4R, preferentially increases acute consumption of high-fat chow in a two-choice paradigm providing high-fat and low-fat chow in Lo...

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“…First, it was reported that AgRP enhances the intake of specifically high-fat diets in rats [32]. In addition, obese mice with ectopic overexpression of Agouti (which mimics the action of AgRP) have enhanced preference for fat meals thus further supporting the hypothesis of strong MC system involvement in native qualitative composition of individually preferred diet [40].…”

Section: Animal Models Of Agrpmentioning

confidence: 89%

“…The results of Vaughan et al suggest that, while decreased MC4R signaling may be consistent with increased food intake, the expression of that behavioral phenotype is highly dependent on the environment. The author concludes that the conditions under which MC4R knock-out mice are hyperphagic thus remain to be addressed [40].…”

Section: Animal Models Of Agrpmentioning

confidence: 99%

Melanocortin system in cancer-related cachexia

et al. 2011

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AbstractThe melanocortin system plays a pivotal role in the regulation of appetite and energy balance. It was recognized to play an important role in the development of cancer-related cachexia, a debilitating condition characterized by progressive body wasting associated with anorexia, increased resting energy expediture and loss of fat as well as lean body mass that cannot be simply prevented or treated by adequate nutritional support.The recent advances in understanding of mechanisms underlying cancer-related cachexia led to consequent recognition of the melanocortin system as an important potential therapeutic target. Several molecules have been made available for animal experiments, including those with oral bioavailability, that act at various checkpoints of the melanocortin system and that might confer singificant benefits for the patients suffering from cancer-related cachexia. The application of melanocortin 4 receptor antagonists/agouti-related peptide agonists has been however restricted to animal models and more pharmacological data will be necessary to progress to clinical trials on humans. Still, pharmacological targeting of the melanocortin system seem to represent an elegant and promising way of treatment of cancer-related cachexia.

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Macronutrient Diet Intake of the Lethal Yellow Agouti (Ay/a) Mouse

Cited by 44 publications

References 11 publications

Pro-opiomelanocortin (POMC)-derived peptides and the regulation of energy homeostasis

Pro-opiomelanocortin (POMC)-derived peptides and the regulation of energy homeostasis

Melanocortin-4 receptor mutations paradoxically reduce preference for palatable foods

Melanocortin system in cancer-related cachexia

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