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Abdominal subcutaneous adipose tissue insulin resistance and lipolysis in patients with non-alcoholic steatohepatitis

BACKGROUND: Systemic insulin resistance (IR) is a primary feature in non-alcoholic steatohepatitis (NASH), however, there remain limited data on tissue-specific insulin sensitivity in vivo. METHODS: We examined tissue-specific (adipose, muscle and liver) insulin sensitivity and inflammation in 16 Eu...

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Autores principales: Armstrong, M J, Hazlehurst, J M, Hull, D, Guo, K, Borrows, S, Yu, J, Gough, S C, Newsome, P N, Tomlinson, J W
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190688/
https://www.ncbi.nlm.nih.gov/pubmed/24962805
http://dx.doi.org/10.1111/dom.12272
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author Armstrong, M J
Hazlehurst, J M
Hull, D
Guo, K
Borrows, S
Yu, J
Gough, S C
Newsome, P N
Tomlinson, J W
author_facet Armstrong, M J
Hazlehurst, J M
Hull, D
Guo, K
Borrows, S
Yu, J
Gough, S C
Newsome, P N
Tomlinson, J W
author_sort Armstrong, M J
collection PubMed
description BACKGROUND: Systemic insulin resistance (IR) is a primary feature in non-alcoholic steatohepatitis (NASH), however, there remain limited data on tissue-specific insulin sensitivity in vivo. METHODS: We examined tissue-specific (adipose, muscle and liver) insulin sensitivity and inflammation in 16 European Caucasian patients with biopsy-confirmed NASH and in 15 healthy controls. All underwent a two-step hyperinsulinaemic euglycaemic clamp incorporating stable isotope measurements of carbohydrate and lipid metabolism with concomitant subcutaneous adipose tissue (SAT) microdialysis. RESULTS: Hepatic and muscle insulin sensitivity were decreased in patients with NASH compared with controls, as demonstrated by reduced suppression of hepatic glucose production and glucose disposal (Gd) rates following insulin infusion. In addition, rates of lipolysis were higher in NASH patients with impaired insulin-mediated suppression of free fatty acid levels. At a tissue specific level, abdominal SAT in patients with NASH was severely insulin resistant, requiring >sixfold more insulin to cause ½-maximal suppression of glycerol release when compared with healthy controls. Furthermore, patients with NASH had significantly higher circulating levels of pro-inflammatory adipocytokines than controls. CONCLUSION: NASH patients have profound IR in the liver, muscle and in particular adipose tissues. This study represents the first in vivo description of dysfunctional SAT in patients with NASH.
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spelling pubmed-41906882014-10-20 Abdominal subcutaneous adipose tissue insulin resistance and lipolysis in patients with non-alcoholic steatohepatitis Armstrong, M J Hazlehurst, J M Hull, D Guo, K Borrows, S Yu, J Gough, S C Newsome, P N Tomlinson, J W Diabetes Obes Metab Original Articles BACKGROUND: Systemic insulin resistance (IR) is a primary feature in non-alcoholic steatohepatitis (NASH), however, there remain limited data on tissue-specific insulin sensitivity in vivo. METHODS: We examined tissue-specific (adipose, muscle and liver) insulin sensitivity and inflammation in 16 European Caucasian patients with biopsy-confirmed NASH and in 15 healthy controls. All underwent a two-step hyperinsulinaemic euglycaemic clamp incorporating stable isotope measurements of carbohydrate and lipid metabolism with concomitant subcutaneous adipose tissue (SAT) microdialysis. RESULTS: Hepatic and muscle insulin sensitivity were decreased in patients with NASH compared with controls, as demonstrated by reduced suppression of hepatic glucose production and glucose disposal (Gd) rates following insulin infusion. In addition, rates of lipolysis were higher in NASH patients with impaired insulin-mediated suppression of free fatty acid levels. At a tissue specific level, abdominal SAT in patients with NASH was severely insulin resistant, requiring >sixfold more insulin to cause ½-maximal suppression of glycerol release when compared with healthy controls. Furthermore, patients with NASH had significantly higher circulating levels of pro-inflammatory adipocytokines than controls. CONCLUSION: NASH patients have profound IR in the liver, muscle and in particular adipose tissues. This study represents the first in vivo description of dysfunctional SAT in patients with NASH. Blackwell Publishing Ltd 2014-07 2014-03-11 /pmc/articles/PMC4190688/ /pubmed/24962805 http://dx.doi.org/10.1111/dom.12272 Text en © 2014 The Authors. Diabetes, Obesity and Metabolism published by JohnWiley & Sons Ltd. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Armstrong, M J
Hazlehurst, J M
Hull, D
Guo, K
Borrows, S
Yu, J
Gough, S C
Newsome, P N
Tomlinson, J W
Abdominal subcutaneous adipose tissue insulin resistance and lipolysis in patients with non-alcoholic steatohepatitis
title Abdominal subcutaneous adipose tissue insulin resistance and lipolysis in patients with non-alcoholic steatohepatitis
title_full Abdominal subcutaneous adipose tissue insulin resistance and lipolysis in patients with non-alcoholic steatohepatitis
title_fullStr Abdominal subcutaneous adipose tissue insulin resistance and lipolysis in patients with non-alcoholic steatohepatitis
title_full_unstemmed Abdominal subcutaneous adipose tissue insulin resistance and lipolysis in patients with non-alcoholic steatohepatitis
title_short Abdominal subcutaneous adipose tissue insulin resistance and lipolysis in patients with non-alcoholic steatohepatitis
title_sort abdominal subcutaneous adipose tissue insulin resistance and lipolysis in patients with non-alcoholic steatohepatitis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190688/
https://www.ncbi.nlm.nih.gov/pubmed/24962805
http://dx.doi.org/10.1111/dom.12272
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