Abdominal subcutaneous adipose tissue insulin resistance and lipolysis in patients with non-alcoholic steatohepatitis
Research output: Contribution to journal › Article › peer-review
Authors
Colleges, School and Institutes
External organisations
- Centre for Endocrinology, Diabetes, and Metabolism (CEDAM); School of Clinical and Experimental Medicine; University of Birmingham; Institute of Biomedical Research; UK
- NIHR/Wellcome Trust Clinical Research Facility; Queen Elizabeth Hospital; Birmingham UK
- School of Sport, Exercise & Rehabilitation Sciences; University of Birmingham; Birmingham UK
- Oxford Centre for Diabetes, Endocrinology and Metabolism, and NIHR Oxford Biomedical Research Centre; Oxford UK
Abstract
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.
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.
Details
Original language | English |
---|---|
Pages (from-to) | 651–660 |
Journal | Diabetes, Obesity and Metabolism |
Volume | 16 |
Issue number | 7 |
Early online date | 11 Mar 2014 |
Publication status | Published - Jul 2014 |
Keywords
- adipose tissue, fatty liver, insulin sensitivity, lipolysis, steatohepatitis