Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1111/dom.12272

Type

Journal article

Journal

Diabetes Obes Metab

Publication Date

07/2014

Volume

16

Pages

651 - 660

Keywords

adipose tissue, fatty liver, insulin sensitivity, lipolysis, steatohepatitis, Adipokines, Adolescent, Adult, Aged, Body Mass Index, Case-Control Studies, Female, Gluconeogenesis, Glucose, Glucose Clamp Technique, Glycerol, Hemoglobin A, Glycosylated, Humans, Hypoglycemic Agents, Inflammation, Insulin, Insulin Resistance, Lipolysis, Liver, Male, Middle Aged, Muscle, Skeletal, Non-alcoholic Fatty Liver Disease, Subcutaneous Fat, Abdominal