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

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. 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.

• Publication year

  2019

• Venue

  Molecular and Cellular Biology

• Publication date

  2019-07-15

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1128/MCB.00210-19PMID 31308132PMCID PMC6766695
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Perilipin 1 (Plin1) deficiency promotes inflammatory responses in lean adipose tissue through lipid dysregulation

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• Lipolysis Triggers a Systemic Insulin Response Essential for Efficient Energy Replenishment of Activated Brown Adipose Tissue in Mice.

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  2018cited by this paper
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  2018cited by this paper
• Insulin action and resistance in obesity and type 2 diabetes

  2017cited by this paper
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  2017cited by this paper
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  2017cited by this paper
• Thermoneutrality decreases thermogenic program and promotes adiposity in high‐fat diet‐fed mice

  2016cited by this paper
• Zfp423 Maintains White Adipocyte Identity through Suppression of the Beige Cell Thermogenic Gene Program.

  2016cited by this paper
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  2016cited by this paper
• Diet‐induced obesity causes insulin resistance in mouse brown adipose tissue

  2015cited by this paper
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  2015cited by this paper
• Myocardin-related transcription factor A regulates conversion of progenitors to beige adipocytes.

  2015cited by this paper
• Lipid-Overloaded Enlarged Adipocytes Provoke Insulin Resistance Independent of Inflammation

  2015influential reference
• The evolution of compositionally and functionally distinct actin filaments

  2015cited by this paper
• Metabolism: Exercise remodels subcutaneous fat tissue and improves metabolism

  2015cited by this paper
• Brown and Beige Fat: Physiological Roles beyond Heat Generation.

  2015cited by this paper
• Adipose tissue browning and metabolic health

  2014cited by this paper
• Arp2/3 complex regulates adipogenesis by controlling cortical actin remodelling.

  2014cited by this paper
• The browning of white adipose tissue: some burning issues.

  2014cited by this paper
• Fat body, fat pad and adipose tissues in invertebrates and vertebrates: the nexus

  2014cited by this paper
• Brown and beige fat: development, function and therapeutic potential

  2013cited by this paper
• Regulation of glucose transport by insulin: traffic control of GLUT4

  2012cited by this paper
• Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human.

  2012cited by this paper
• MitoNEET-driven alterations in adipocyte mitochondrial activity reveal a crucial adaptive process that preserves insulin sensitivity in obesity

  2012cited by this paper
• GLUT4 exocytosis

  2011cited by this paper
• Different metabolic responses of human brown adipose tissue to activation by cold and insulin.

  2011cited by this paper
• Inflammation Is Necessary for Long-Term but Not Short-Term High-Fat Diet–Induced Insulin Resistance

  2011cited by this paper
• Identification and importance of brown adipose tissue in adult humans.

  2009cited by this paper
• Cold-activated brown adipose tissue in healthy men.

  2009cited by this paper
• Rapid activation of Akt2 is sufficient to stimulate GLUT4 translocation in 3T3-L1 adipocytes.

  2008cited by this paper
• Transcriptional control of brown fat determination by PRDM16.

  2007cited by this paper
• Development of a cy3-labeled glucose bioprobe and its application in bioimaging and screening for anticancer agents.

  2007cited by this paper
• Endocrine functions of adipose tissue.

  2007cited by this paper
• The actin depolymerizing factor n-cofilin is essential for neural tube morphogenesis and neural crest cell migration.

  2005cited by this paper
• AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab GTPase-activating protein domain.

  2005cited by this paper
• Phosphatidylinositol 4,5-Bisphosphate Regulates Adipocyte Actin Dynamics and GLUT4 Vesicle Recycling*

  2004cited by this paper
• Brown adipose tissue: function and physiological significance.

  2004influential reference
• Brown adipose tissue: function and physiological significance.

  2004cited by this paper
• Insulin-stimulated Phosphorylation of a Rab GTPase-activating Protein Regulates GLUT4 Translocation*

  2003cited by this paper
• Insulin Stimulates Actin Comet Tails on Intracellular GLUT4-containing Compartments in Differentiated 3T3L1 Adipocytes* 210

  2001cited by this paper
• Insulin-stimulated GLUT4 Translocation in Adipocytes Is Dependent upon Cortical Actin Remodeling* 210

  2001cited by this paper
• Cytoskeleton: Evolution in bacteria

  2001cited by this paper
• Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver

  2001cited by this paper
• GLUT4 overexpression in db/db mice dose-dependently ameliorates diabetes but is not a lifelong cure.

  2001cited by this paper
• Gelsolin and ADF/cofilin enhance the actin dynamics of motile cells.

  2000cited by this paper
• Specific elevation of transcript levels of particular protein subtypes induced in brown adipose tissue by cold exposure.

  2000cited by this paper
• Diabetes: Insulin resistance and obesity

  1999cited by this paper
• Signaling to the actin cytoskeleton.

  1998cited by this paper
• Hemostatic, inflammatory, and fibroblast responses are blunted in mice lacking gelsolin.

  1995cited by this paper
• Enhanced peripheral glucose utilization in transgenic mice expressing the human GLUT4 gene.

  1994cited by this paper
• Increased expression of glucose transporter GLUT-4 in brown adipose tissue of fasted rats after cold exposure.

  1993cited by this paper
• Cold exposure increases glucose utilization and glucose transporter expression in brown adipose tissue.

  1992cited by this paper
• Fibronectin modulation of cell shape and lipogenic gene expression in 3T3-adipocytes.

  1983cited by this paper
• Decreases in tubulin and actin gene expression prior to morphological differentiation of 3T3 adipocytes.

  1982cited by this paper
• The Insulin Receptor: Its Role in Insulin Resistance of Obesity and Diabetes

  1976cited by this paper

• Modulating cell surface chemistry through mild reduction reinforces extracellular-to-intracellular transmission forces and mechano-signaling.

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  2026cites this paper
• Unraveling the complexities of diet induced obesity and glucolipid dysfunction in metabolic syndrome

  2025cites this paper
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• Proteomic Profiling Reveals Alterations in Metabolic and Cellular Pathways in Severe Obesity and Following Metabolic Bariatric Surgery.

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  2025cites this paper
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