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Preproghrelin expression is a key target for insulin action on adipogenesis.

Gurriarán Rodríguez, Uxía; AL-MASSADI IGLESIAS, OMAR; Crujeiras Martínez, Ana Belén; Seoane Mosteiro, Carlos; Amil-Diz, María; Beiroa Tarrío, Daniel; Nogueiras Pozo, Rubén; Seoane Camino, Luisa Maria; Gallego, Rosalía; Pazos Randulfe, Yolanda; Casanueva Freijo, Felipe; Pérez Camiña, Jesús
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URI: http://hdl.handle.net/20.500.11940/5528
PMID: 21690170
DOI: 10.1530/JOE-11-0233
ISSN: 0022-0795
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Preproghrelin expression is a key target for insulin action on adipogenesis. (253.2Kb)
Acceso a la versión del editor (5.798Kb)
Fecha de publicación
2011
Título de revista
JOURNAL OF ENDOCRINOLOGY
Tipo de contenido
Artigo
MeSH
Male | Animals | Mice | Insulin | 3T3-L1 Cells | RNA, Small Interfering | Adipocytes | Adipogenesis | Peptide Hormones | Protein Precursors
Resumen
This study aimed to investigate the role of preproghrelin-derived peptides in adipogenesis. Immunocytochemical analysis of 3T3-L1 adipocyte cells showed stronger preproghrelin expression compared with that observed in 3T3-L1 preadipocyte cells. Insulin promoted this expression throughout adipogenesis identifying mTORC1 as a critical downstream substrate for this profile. The role of preproghrelin-derived peptides on the differentiation process was supported by preproghrelin knockdown experiments, which revealed its contribution to adipogenesis. Neutralization of endogenous O-acyl ghrelin (acylated ghrelin), unacylated ghrelin, and obestatin by specific antibodies supported their adipogenic potential. Furthermore, a parallel increase in the expression of ghrelin-associated enzymatic machinery, prohormone convertase 1/3 (PC1/3) and membrane-bound O-acyltransferase 4 (MBOAT4), was dependent on the expression of preproghrelin in the course of insulin-induced adipogenesis. The coexpression of preproghrelin system and their receptors, GHSR1a and GPR39, during adipogenesis supports an autocrine/paracrine role for these peptides. Preproghrelin, PC1/3, and MBOAT4 exhibited dissimilar expression depending on the white fat depot, revealing their regulation in a positive energy balance situation in mice. The results underscore a key role for preproghrelin-derived peptides on adipogenesis through an autocrine/paracrine mechanism.

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