Artículo
5-HT obesity medication efficacy via POMC activation is maintained during aging
Burke, Luke K.; Doslikova, Barbora; D'agostino, Giuseppe; Garfield, Alastair S.; Farooq, Gala; Burdakov, Denis; Low, Malcolm J.; Rubinstein, Marcelo
; Evans, Mark L.; Billups, Brian; Heisler, Lora K.
![Icon](/themes/CONICETDigital/images/conicet.png)
Fecha de publicación:
22/07/2014
Editorial:
Endocrine Society
Revista:
Endocrinology
ISSN:
0013-7227
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The phenomenon commonly described as the middle-age spread is the result of elevated adiposity accumulation throughout adulthood until late middle-age. It is a clinical imperative to gain a greater understanding of the underpinnings of age-dependent obesity and, in turn, how these mechanisms may impact the efficacy of obesity treatments. In particular, both obesity and aging are associated with rewiring of a principal brain pathway modulating energy homeostasis, promoting reduced activity of satiety pro-opiomelanocortin (POMC) neurons within the arcuate nucleus of the hypothalamus (ARC). Using a selective ARC-deficient POMC mouse line, here we report that former obesity medications augmenting endogenous 5-hydroxytryptamine (5-HT) activity d-fenfluramine and sibutramine require ARC POMC neurons to elicit therapeutic appetite-suppressive effects. We next investigated whether age-related diminished ARC POMC activity therefore impacts the potency of 5-HT obesity pharmacotherapies, lorcaserin, d-fenfluramine, and sibutramine and report that all compounds reduced food intake to a comparable extent in both chow-fed young lean (3-5 months old) and middle-aged obese (12-14 months old) male and female mice. We provide a mechanism through which 5-HT anorectic potency is maintained with age, via preserved 5-HT-POMC appetitive anatomical machinery. Specifically, the abundance and signaling of the primary 5-HT receptor influencing appetite via POMC activation, the 5-HT2CR, is not perturbed with age. These data reveal that although 5-HT obesity medications require ARC POMC neurons to achieve appetitive effects, the anorectic efficacy is maintained with aging, findings of clinical significance to the global aging obese population.
Palabras clave:
Serotonina
,
Pomc
,
Ratón Transgénico
,
Obesidad
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Colecciones
Articulos(INGEBI)
Articulos de INST.DE INVEST.EN ING.GENETICA Y BIOL.MOLECULAR "DR. HECTOR N TORRES"
Articulos de INST.DE INVEST.EN ING.GENETICA Y BIOL.MOLECULAR "DR. HECTOR N TORRES"
Citación
Burke, Luke K.; Doslikova, Barbora; D'agostino, Giuseppe; Garfield, Alastair S.; Farooq, Gala; et al.; 5-HT obesity medication efficacy via POMC activation is maintained during aging; Endocrine Society; Endocrinology; 155; 10; 22-7-2014; 3732-3738
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