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Ectopic Fat Accumulation and Distant Organ-Specific Insulin Resistance in Japanese People with Nonalcoholic Fatty Liver Disease
OBJECTIVE: The aim of this study was to examine the association between ectopic fat and organ-specific insulin resistance (IR) in insulin-target organs in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: Organ-specific IR in the liver (hepatic glucose production (HGP)×fasting plasma...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961287/ https://www.ncbi.nlm.nih.gov/pubmed/24651470 http://dx.doi.org/10.1371/journal.pone.0092170 |
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author | Kato, Ken-ichiro Takamura, Toshinari Takeshita, Yumie Ryu, Yasuji Misu, Hirofumi Ota, Tsuguhito Tokuyama, Kumpei Nagasaka, Shoichiro Matsuhisa, Munehide Matsui, Osamu Kaneko, Shuichi |
author_facet | Kato, Ken-ichiro Takamura, Toshinari Takeshita, Yumie Ryu, Yasuji Misu, Hirofumi Ota, Tsuguhito Tokuyama, Kumpei Nagasaka, Shoichiro Matsuhisa, Munehide Matsui, Osamu Kaneko, Shuichi |
author_sort | Kato, Ken-ichiro |
collection | PubMed |
description | OBJECTIVE: The aim of this study was to examine the association between ectopic fat and organ-specific insulin resistance (IR) in insulin-target organs in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: Organ-specific IR in the liver (hepatic glucose production (HGP)×fasting plasma insulin (FPI) and suppression of HGP by insulin [%HGP]), skeletal muscle (insulin-stimulated glucose disposal [Rd]), and adipose tissue (suppression of FFA by insulin [%FFA]) was measured in 69 patients with NAFLD using a euglycemic hyperinsulinemic clamp with tracer infusion ([6,6-(2)H(2)]glucose). Liver fat, intramyocellular lipid (IMCL), and body composition were measured by liver biopsy, proton magnetic resonance spectroscopy, and bioelectrical impedance analysis, respectively. RESULTS: HGP×FPI was significantly correlated with Rd (r = −0.57, P<0.001), %HGP with %FFA (r = 0.38, P<0.01), and Rd with %FFA (r = 0.27, P<0.05). Liver steatosis score was negatively associated with Rd (r = −0.47, P<0.001) as well as with HGP×FPI (r = 0.43, P<0.001). Similarly, intrahepatic lipid was negatively associated with Rd (r = −0.32, P<0.05). IMCL was not associated with Rd (r = −0.16, P = 0.26). Fat mass and its percentage were associated with HGP×FPI (r = 0.50, P<0.001; r = 0.48, P<0.001, respectively) and Rd (r = −0.59, P<0.001; r = −0.52, P<0.001, respectively), but not with %FFA (r = −0.21, P = 0.10; r = −0.001, P = 0.99, respectively). CONCLUSION: Unexpectedly, fat accumulation in the skeletal muscle and adipose tissue was not associated with organ-specific IR. Instead, liver fat was associated not only with hepatic IR but also with skeletal muscle IR, suggesting a central role of fatty liver in systemic IR and that a network exists between liver and skeletal muscle. |
format | Online Article Text |
id | pubmed-3961287 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39612872014-03-27 Ectopic Fat Accumulation and Distant Organ-Specific Insulin Resistance in Japanese People with Nonalcoholic Fatty Liver Disease Kato, Ken-ichiro Takamura, Toshinari Takeshita, Yumie Ryu, Yasuji Misu, Hirofumi Ota, Tsuguhito Tokuyama, Kumpei Nagasaka, Shoichiro Matsuhisa, Munehide Matsui, Osamu Kaneko, Shuichi PLoS One Research Article OBJECTIVE: The aim of this study was to examine the association between ectopic fat and organ-specific insulin resistance (IR) in insulin-target organs in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: Organ-specific IR in the liver (hepatic glucose production (HGP)×fasting plasma insulin (FPI) and suppression of HGP by insulin [%HGP]), skeletal muscle (insulin-stimulated glucose disposal [Rd]), and adipose tissue (suppression of FFA by insulin [%FFA]) was measured in 69 patients with NAFLD using a euglycemic hyperinsulinemic clamp with tracer infusion ([6,6-(2)H(2)]glucose). Liver fat, intramyocellular lipid (IMCL), and body composition were measured by liver biopsy, proton magnetic resonance spectroscopy, and bioelectrical impedance analysis, respectively. RESULTS: HGP×FPI was significantly correlated with Rd (r = −0.57, P<0.001), %HGP with %FFA (r = 0.38, P<0.01), and Rd with %FFA (r = 0.27, P<0.05). Liver steatosis score was negatively associated with Rd (r = −0.47, P<0.001) as well as with HGP×FPI (r = 0.43, P<0.001). Similarly, intrahepatic lipid was negatively associated with Rd (r = −0.32, P<0.05). IMCL was not associated with Rd (r = −0.16, P = 0.26). Fat mass and its percentage were associated with HGP×FPI (r = 0.50, P<0.001; r = 0.48, P<0.001, respectively) and Rd (r = −0.59, P<0.001; r = −0.52, P<0.001, respectively), but not with %FFA (r = −0.21, P = 0.10; r = −0.001, P = 0.99, respectively). CONCLUSION: Unexpectedly, fat accumulation in the skeletal muscle and adipose tissue was not associated with organ-specific IR. Instead, liver fat was associated not only with hepatic IR but also with skeletal muscle IR, suggesting a central role of fatty liver in systemic IR and that a network exists between liver and skeletal muscle. Public Library of Science 2014-03-20 /pmc/articles/PMC3961287/ /pubmed/24651470 http://dx.doi.org/10.1371/journal.pone.0092170 Text en © 2014 Kato et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Kato, Ken-ichiro Takamura, Toshinari Takeshita, Yumie Ryu, Yasuji Misu, Hirofumi Ota, Tsuguhito Tokuyama, Kumpei Nagasaka, Shoichiro Matsuhisa, Munehide Matsui, Osamu Kaneko, Shuichi Ectopic Fat Accumulation and Distant Organ-Specific Insulin Resistance in Japanese People with Nonalcoholic Fatty Liver Disease |
title | Ectopic Fat Accumulation and Distant Organ-Specific Insulin Resistance in Japanese People with Nonalcoholic Fatty Liver Disease |
title_full | Ectopic Fat Accumulation and Distant Organ-Specific Insulin Resistance in Japanese People with Nonalcoholic Fatty Liver Disease |
title_fullStr | Ectopic Fat Accumulation and Distant Organ-Specific Insulin Resistance in Japanese People with Nonalcoholic Fatty Liver Disease |
title_full_unstemmed | Ectopic Fat Accumulation and Distant Organ-Specific Insulin Resistance in Japanese People with Nonalcoholic Fatty Liver Disease |
title_short | Ectopic Fat Accumulation and Distant Organ-Specific Insulin Resistance in Japanese People with Nonalcoholic Fatty Liver Disease |
title_sort | ectopic fat accumulation and distant organ-specific insulin resistance in japanese people with nonalcoholic fatty liver disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961287/ https://www.ncbi.nlm.nih.gov/pubmed/24651470 http://dx.doi.org/10.1371/journal.pone.0092170 |
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