Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 65, Issue 17, Pages 2721-2731Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-008-8104-4
Keywords
hypothalamus; adrenal gland; longevity; polymorphism
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Funding
- NIDDK NIH HHS [P30 DK072476, P30 DK072476-04] Funding Source: Medline
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The Agouti-Related Protein (AgRP) is a powerful orexigenic peptide that increases food intake when ubiquitously overexpressed or when administered centrally. AgRP-deficiency, on the other hand, leads to increased metabolic rate and a longer lifespan when mice consume a high fat diet. In humans, AgRP polymorphisms have been consistently associated with resistance to fatness in Blacks and Whites and resistance to the development of type-2 diabetes in African Blacks. Systemically administered AgRP accumulates in the liver, the adrenal gland and fat tissue while recent findings suggest that AgRP may also have inverse agonist effects, both centrally and peripherally. AgRP could thus modulate energy balance via different actions. Its absence or reduced functionality may offer a benefit both in terms of bringing about negative energy balance in obesigenic environments, as well as leading to an increased lifespan.
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