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Lipid-Overloaded Enlarged Adipocytes Provoke Insulin Resistance Independent of Inflammation

Cited 104 time in Web of Science Cited 103 time in Scopus
Authors
Kim, Jong In; Huh, Jin Young; Sohn, Jee Hyung; Choe, Sung Sik; Lee, Yun Sok; Lim, Chun Yan; Jo, Ala; Park, Seung Bum; Han, Weiping; Kim, Jae Bum
Issue Date
2015
Publisher
American Society for Microbiology
Citation
Molecular and Cellular Biology, vol.35 no.10, pp. 1686-1699
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.
Language
English
URI
https://hdl.handle.net/10371/95472
DOI
https://doi.org/10.1128/MCB.01321-14
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College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
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