The insulin‐PI3K‐Rac1 axis contributes to terminal adipocyte differentiation through regulation of actin cytoskeleton dynamics

Adipocyte differentiation is accompanied by a pronounced change in the actin cytoskeleton characterized by the reorganization of filamentous (F)‐actin stress fibers into cortical F‐actin structures. We previously showed that depolymerization of F‐actin stress fibers induced by inactivation of RhoA–R...

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Bibliographic Details
Published in:Genes to cells : devoted to molecular & cellular mechanisms 2020-03, Vol.25 (3), p.165-174
Main Authors: Kunitomi, Haruko, Oki, Yoshinao, Onishi, Nobuyuki, Kano, Koichiro, Banno, Kouji, Aoki, Daisuke, Saya, Hideyuki, Nobusue, Hiroyuki
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Actin
actin cytoskeleton
Actin Cytoskeleton - metabolism
adipocyte differentiation
Adipocytes
Adipocytes - metabolism
Adipogenesis
Animals
Cell Differentiation
Cells, Cultured
Cortex
Cytoskeleton
Depolymerization
Fibers
Insulin
Insulin - metabolism
Mice
Neuropeptides - metabolism
Phosphatidylinositol 3-Kinase - metabolism
phosphatidylinositol 3‐kinase (PI3K)
Rac1
rac1 GTP-Binding Protein - metabolism
Rac1 protein
RhoA protein
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Summary:Adipocyte differentiation is accompanied by a pronounced change in the actin cytoskeleton characterized by the reorganization of filamentous (F)‐actin stress fibers into cortical F‐actin structures. We previously showed that depolymerization of F‐actin stress fibers induced by inactivation of RhoA–ROCK (Rho‐associated kinase) signaling acts as a trigger for adipocyte differentiation. The relevance and underlying mechanism of the formation of cortical F‐actin structures from depolymerized actin during adipocyte differentiation have remained unclear, however. We have now examined the mechanistic relation between actin dynamics and adipogenic induction. Transient exposure to the actin‐depolymerizing agent latrunculin A (LatA) supported the formation of adipocyte‐associated cortical actin structures and the completion of terminal adipocyte differentiation in the presence of insulin, whereas long‐term exposure to LatA prevented such actin reorganization as well as terminal adipogenesis. Moreover, these effects of insulin were prevented by inhibition of phosphatidylinositol 3‐kinase (PI3K)–Rac1 signaling and the actin‐related protein 2/3 (Arp2/3) complex which is a critical component of the cortical actin networks. Our findings thus suggest that the insulin‐PI3K‐Rac1 axis leads to the formation of adipocyte‐associated cortical actin structures which is essential for the completion of adipocyte differentiation. Inactivation of RhoA‐ROCK signaling induces the expression of PPARγ and the initiation of adipogenesis as a result of depolymerization of F‐actin stress fibers. The insulin‐PI3K‐Rac1 axis then leads to the completion of adipogenesis by regulating the formation of adipocyte‐associated cortical actin structures from depolymerized actin.
ISSN:1356-9597
1365-2443
DOI:10.1111/gtc.12747