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Melanocortin-4 receptor in sheep: a potential site for therapeutic intervention in disease models
J L Sartin1, C G Wagner, D L Marks
1Department Anatomy, Physiology & Pharmacology, Auburn University, AL 36849, USA. sartijl@vetmed.auburn.edu
Abstract:
Reduced appetite combined with increased metabolic rate and decreased lean body mass is a major consequence of disease and other stressors. Studies in rodent species suggest that an understanding of appetite regulation may provide methodologies for intervention to prevent the deterioration of body mass such as observed with cancer or infectious diseases. For example, melanocortin-4 receptor (MC4-R) antagonists have shown a remarkable ability to reverse or prevent cachexia in rodents with sarcoma or treated with endotoxin. Studies in sheep have indicated that a number of peptide neurotransmitters may have a role in regulating appetite in this species. For example, agouti related protein mRNA and protein levels are dramatically altered with fasting in sheep. Moreover, agouti related protein, neuropeptide Y, melanin concentrating hormone and orexin are potent stimuli to increase feed intake in sheep. Recent studies have indicated that one of these neurotransmitters, NPY, can work in principal to improve appetite in endotoxin-treated sheep. Current studies are examining the role that MC4-R antagonists may have in the prevention or correction of body mass wasting diseases as well as practical applications in animal production.
Insights
Appetite regulation research offers new ways to prevent body mass loss during illness. Melanocortin-4 receptor (MC4-R) antagonists show promise in reversing cachexia in animal models.
Area of Science:
- Animal Science
- Neuroscience
- Physiology
Background:
- Reduced appetite, increased metabolism, and lean body mass loss are common in disease and stress.
- Understanding appetite regulation is key to preventing detrimental body mass wasting.
- Rodent studies show melanocortin-4 receptor (MC4-R) antagonists can prevent cachexia.
Purpose of the Study:
- To investigate appetite regulation in sheep, focusing on peptide neurotransmitters.
- To examine the role of neuropeptide Y (NPY) in appetite control in endotoxin-treated sheep.
- To explore the potential of MC4-R antagonists in preventing or correcting body mass wasting diseases and their application in animal production.
Main Methods:
- Studied alterations in agouti related protein mRNA and protein levels during fasting in sheep.
- Investigated the appetite-stimulating effects of various peptide neurotransmitters, including agouti related protein, neuropeptide Y, melanin concentrating hormone, and orexin.
- Examined the effect of NPY on appetite in endotoxin-treated sheep.
Main Results:
- Fasting significantly alters agouti related protein mRNA and protein levels in sheep.
- Several peptide neurotransmitters (agouti related protein, NPY, melanin concentrating hormone, orexin) potently stimulate feed intake in sheep.
- NPY was found to improve appetite in endotoxin-treated sheep.
Conclusions:
- Peptide neurotransmitters play a crucial role in appetite regulation in sheep.
- NPY is a significant factor in appetite stimulation, particularly in disease states.
- MC4-R antagonists represent a promising therapeutic strategy for cachexia and have potential applications in animal agriculture.
