AgRP-deficiency could lead to increased lifespan.
The Agouti-related protein (AgRP) is a central orexigenic peptide leading to increased food intake when ubiquitously overexpressed. AgRP-deficient (AgRP(-/-)) mice have either no phenotype or present an age-related leanness. In this study, AgRP(-/-) mice were fed alternate high fat or low fat diets in an effort to determine whether AgRP is a mediating factor for the effects of dietary fat on metabolic parameters. There were no striking metabolic differences between AgRP(-/-) and the equally obese wild type littermates but AgRP(-/-) mice displayed a significantly longer lifespan. The point estimate of median survival for the AgRP(-/-) group was 9.8% greater while the significantly low hazard ratio (0.494) suggests that mortality incidence of AgRP(-/-) mice is less than one-half that of the wild type reference population. It is concluded that although AgRP(-/-) mice become morbidly obese consuming a high fat diet (a landmark feature for a shortened lifespan), they seem to overcome obesity- and age-related pathologies and live significantly longer than their metabolically similar wild type littermates.
Redmann
Stephen M
SM
Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
Argyropoulos
George
G
D054369:Agouti-Related Protein; D000818:Animals; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009765:Obesity / Q000235:genetics; D013851:Thinness / Q000235:genetics*
C515198:AGRP protein, human; D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D004041:Dietary Fats; D036341:Intercellular Signaling Peptides and Proteins