Antiobesity Action of ACAM by Modulating the Dynamics of Cell Adhesion and Actin Polymerization in Adipocytes

Diabetes. 2016 May;65(5):1255-67. doi: 10.2337/db15-1304. Epub 2016 Mar 8.

Abstract

Coxsackie virus and adenovirus receptor-like membrane protein (CLMP) was identified as the tight junction-associated transmembrane protein of epithelial cells with homophilic binding activities. CLMP is also recognized as adipocyte adhesion molecule (ACAM), and it is upregulated in mature adipocytes in rodents and humans with obesity. Here, we present that aP2 promoter-driven ACAM transgenic mice are protected from obesity and diabetes with the prominent reduction of adipose tissue mass and smaller size of adipocytes. ACAM is abundantly expressed on plasma membrane of mature adipocytes and associated with formation of phalloidin-positive polymerized form of cortical actin (F-actin). By electron microscopy, the structure of zonula adherens with an intercellular space of ∼10-20 nm was observed with strict parallelism of the adjoining cell membranes over distances of 1-20 μm, where ACAM and γ-actin are abundantly expressed. The formation of zonula adherens may increase the mechanical strength, inhibit the adipocyte hypertrophy, and improve the insulin sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Actin Cytoskeleton / metabolism*
  • Actin Cytoskeleton / pathology
  • Actin Cytoskeleton / ultrastructure
  • Adherens Junctions / metabolism*
  • Adherens Junctions / pathology
  • Adherens Junctions / ultrastructure
  • Adipocytes, White / cytology
  • Adipocytes, White / metabolism*
  • Adipocytes, White / pathology
  • Adipocytes, White / ultrastructure
  • Adiposity*
  • Animals
  • Cell Adhesion
  • Cell Size
  • Coxsackie and Adenovirus Receptor-Like Membrane Protein / genetics
  • Coxsackie and Adenovirus Receptor-Like Membrane Protein / metabolism*
  • Diabetes Mellitus / etiology
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / pathology
  • Diabetes Mellitus / prevention & control
  • Diet, High-Fat / adverse effects
  • Dietary Sucrose / adverse effects
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Microscopy, Immunoelectron
  • Obesity / etiology
  • Obesity / metabolism
  • Obesity / pathology
  • Obesity / prevention & control*
  • Recombinant Fusion Proteins / metabolism
  • Up-Regulation*

Substances

  • CLMP protein, mouse
  • Coxsackie and Adenovirus Receptor-Like Membrane Protein
  • Dietary Sucrose
  • Recombinant Fusion Proteins