Rab18 Dynamics in Adipocytes in Relation to Lipogenesis, Lipolysis and Obesity
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Author
Pulido, Marina R.
Díaz-Ruiz, Alberto
Jiménez-Gómez, Yolanda
García-Navarro, Socorro
Gracia-Navarro, F.
Frühbeck, Gema
Vázquez Martínez, Rafael
Tinahones, Francisco J.
Malagón, María M.
López-Miranda, José
Publisher
Public Libray of Science (PLOS)Date
2011Subject
Rab 18Lipid droplets
Lipogenesis
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Show full item recordAbstract
Lipid droplets (LDs) are organelles that coordinate lipid storage and mobilization, both processes being especially important
in cells specialized in managing fat, the adipocytes. Proteomic analyses of LDs have consistently identified the small GTPase
Rab18 as a component of the LD coat. However, the specific contribution of Rab18 to adipocyte function remains to be
elucidated. Herein, we have analyzed Rab18 expression, intracellular localization and function in relation to the metabolic
status of adipocytes. We show that Rab18 production increases during adipogenic differentiation of 3T3-L1 cells. In addition,
our data show that insulin induces, via phosphatidylinositol 3-kinase (PI3K), the recruitment of Rab18 to the surface of LDs.
Furthermore, Rab18 overexpression increased basal lipogenesis and Rab18 silencing impaired the lipogenic response to
insulin, thereby suggesting that this GTPase promotes fat accumulation in adipocytes. On the other hand, studies of the badrenergic
receptor agonist isoproterenol confirmed and extended previous evidence for the participation of Rab18 in
lipolysis. Together, our data support the view that Rab18 is a common mediator of lipolysis and lipogenesis and suggests
that the endoplasmic reticulum (ER) is the link that enables Rab18 action on these two processes. Finally, we describe, for
the first time, the presence of Rab18 in human adipose tissue, wherein the expression of this GTPase exhibits sex- and
depot-specific differences and is correlated to obesity. Taken together, these findings indicate that Rab18 is involved in
insulin-mediated lipogenesis, as well as in b-adrenergic-induced lipolysis, likely facilitating interaction of LDs with ER
membranes and the exchange of lipids between these compartments. A role for Rab18 in the regulation of adipocyte
biology under both normal and pathological conditions is proposed.