During Adipocyte Remodeling, Lipid Droplet Configurations Regulate Insulin Sensitivity through F-Actin and G-Actin Reorganization

ABSTRACT

Adipocytes have unique morphological traits in insulin sensitivity control. However, how the appearance of adipocytes can determine insulin sensitivity has not been understood. Here, we demonstrate that actin cytoskeleton reorganization upon lipid droplet (LD) configurations in adipocytes plays important roles in insulin-dependent glucose uptake by regulating GLUT4 trafficking. Compared to white adipocytes, brown/beige adipocytes with multilocular LDs exhibited well-developed filamentous actin (F-actin) structure and potentiated GLUT4 translocation to the plasma membrane in the presence of insulin. In contrast, LD enlargement and unilocularization in adipocytes downregulated cortical F-actin formation, eventually leading to decreased F-actin-to-globular actin (G-actin) ratio and suppression of insulin-dependent GLUT4 trafficking. Pharmacological inhibition of actin polymerization accompanied with impaired F/G-actin dynamics reduced glucose uptake in adipose tissue and conferred systemic insulin resistance in mice. Thus, our study reveals that adipocyte remodeling with different LD configurations could be an important factor to determine insulin sensitivity by modulating F/G-actin dynamics.

KEYWORDS:

• actin
• adipocytes
• cytoskeleton
• GLUT4
• glucose transport
• insulin sensitivity
• lipid droplet

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SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at https://doi.org/10.1128/MCB.00210-19.

ACKNOWLEDGMENTS

Fluorescent glucose bioprobe (GB-Cy3) was kindly provided by Seung-Bum Park, Department of Chemistry, Seoul National University, Seoul, South Korea. EGFP-N1-gelsolin vector was kindly provided by Jung-Woong Kim, Department of Life Science, Chung Ang University, Seoul, South Korea. Lentiviral vectors (myc-GLUT4-mCherry, HA-GLUT4, and GLUT4-EGFP) were kindly provided by Weiping Han, Singapore BioImaging Consortium, A*STAR, Singapore.

This study was supported by the National Creative Research Initiative Program (2011-0018312), funded by the Ministry of Education, Science, and Technology.

We have no conflicts of interest to declare.