Lipid-overloaded enlarged adipocytes provoke insulin resistance independent of inflammation.

Abstract

In obesity, adipocyte hypertrophy and proinflammatory responses are closely associated with the development of insulin resistance in adipose tissue. However, it is largely unknown whether adipocyte hypertrophy per se might be sufficient to provoke insulin resistance in obese adipose tissue. Here, we demonstrate that lipid-overloaded hypertrophic adipocytes are insulin resistant independent of adipocyte inflammation. Treatment with saturated or monounsaturated fatty acids resulted in adipocyte hypertrophy, but proinflammatory responses were observed only in adipocytes treated with saturated fatty acids. Regardless of adipocyte inflammation, hypertrophic adipocytes with large and unilocular lipid droplets exhibited impaired insulin-dependent glucose uptake, associated with defects in GLUT4 trafficking to the plasma membrane. Moreover, Toll-like receptor 4 mutant mice (C3H/HeJ) with high-fat-diet-induced obesity were not protected against insulin resistance, although they were resistant to adipose tissue inflammation. Together, our in vitro and in vivo data suggest that adipocyte hypertrophy alone may be crucial in causing insulin resistance in obesity.

• Authors: Jong In Kim, Jin Young Huh, Jee Hyung Sohn, Sung Sik Choe, Yun Sok Lee, Chun Yan Lim, Ala Jo, Seung Bum Park, Weiping Han, Jae Bum Kim
• Journal: Molecular and cellular biology (Mol Cell Biol) Vol. 35 Issue 10 Pg. 1686-99 (May 2015) ISSN: 1098-5549 [Electronic] United States
• PMID: 25733684 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• Cytokines
• Dietary Fats
• Fatty Acids, Monounsaturated
• Fatty Acids, Nonesterified
• Glucose Transporter Type 4
• Slc2a4 protein, mouse
• Tlr4 protein, mouse
• Toll-Like Receptor 4

Topics

• 3T3-L1 Cells
• Adipocytes (drug effects, immunology)
• Animals
• Cell Membrane (metabolism)
• Cytokines (metabolism)
• Dietary Fats (administration & dosage)
• Fatty Acids, Monounsaturated (pharmacology)
• Fatty Acids, Nonesterified (pharmacology)
• Glucose Transporter Type 4 (metabolism)
• In Vitro Techniques
• Insulin Resistance
• Lipid Droplets (metabolism)
• Male
• Mice
• Models, Biological
• Molecular Sequence Data
• Obesity (chemically induced, metabolism)
• Toll-Like Receptor 4 (genetics, metabolism)