title: Preproghrelin expression is a key target for insulin action on adipogenesis.
abstract: 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.
authors.affiliation: Área de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Hospital Clínico Universitario de Santiago, Servicio Gallego de Salud (SERGAS), Santiago de Compostela, Spain.
authors.forename: Uxía
authors.initials: U
authors.lastname: Gurriarán-Rodríguez
authors.forename: Omar
authors.initials: O
authors.lastname: Al-Massadi
authors.forename: Ana Belén
authors.initials: AB
authors.lastname: Crujeiras
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Mosteiro
authors.forename: María
authors.initials: M
authors.lastname: Amil-Diz
authors.forename: Daniel
authors.initials: D
authors.lastname: Beiroa
authors.forename: Rubén
authors.initials: R
authors.lastname: Nogueiras
authors.forename: Luisa María
authors.initials: LM
authors.lastname: Seoane
authors.forename: Rosalía
authors.initials: R
authors.lastname: Gallego
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Pazos
authors.forename: Felipe F
authors.initials: FF
authors.lastname: Casanueva
authors.forename: Jesús P
authors.initials: JP
authors.lastname: Camiña
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D007328:Insulin / Q000378:metabolism*; D008297:Male; D051379:Mice; D036361:Peptide Hormones / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D034741:RNA, Small Interfering
chemical_list: D007328:Insulin; D036361:Peptide Hormones; D011498:Protein Precursors; D034741:RNA, Small Interfering