Preproghrelin expression is a key target for insulin action on adipogenesis
| Autor: | Luisa M. Seoane, Rubén Nogueiras, Carlos S. Mosteiro, Jesus P. Camiña, Uxía Gurriarán-Rodríguez, María Amil-Diz, Yolanda Pazos, Rosalía Gallego, Ana B. Crujeiras, Omar Al-Massadi, Felipe F. Casanueva, Daniel Beiroa |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Peptide Hormones Endocrinology Diabetes and Metabolism mTORC1 Biology Mice chemistry.chemical_compound Paracrine signalling Endocrinology 3T3-L1 Cells Internal medicine Adipocyte Adipocytes medicine Animals Insulin Protein Precursors RNA Small Interfering Autocrine signalling Gene knockdown Adipogenesis Obestatin chemistry Ghrelin |
| Zdroj: | Journal of Endocrinology. 210:R1-R7 |
| ISSN: | 1479-6805 0022-0795 |
| DOI: | 10.1530/joe-11-0233 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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