title: Intrahepatic insulin exposure, intrahepatocellular lipid and regional body fat in nonalcoholic fatty liver disease.
abstract: BACKGROUND
  Insulin is pivotal in regulating hepatic lipid synthesis, metabolism, and export.
  
  
  OBJECTIVE
  We tested the hypothesis that intrahepatic insulin exposure is an important determinant of intrahepatocellular lipid (IHCL), taking into account regional adiposity and both glucoregulatory and antilipolytic insulin sensitivity.
  
  
  METHODS
  We compared 21 European males with known nonalcoholic fatty liver disease (NAFLD) with 19 healthy male controls. Insulin sensitivity, secretion, and percentage hepatic extraction were derived from iv glucose tolerance test (IVGTT) glucose, insulin, and C-peptide concentrations. Intrahepatic insulin exposure was calculated as percentage hepatic insulin extraction multiplied by basal or IVGTT insulin secretion. IHCL was quantified by proton magnetic resonance spectroscopy. Total and regional adipose tissue was measured using whole body magnetic resonance imaging.
  
  
  RESULTS
  Percentage hepatic extraction of newly secreted insulin differed between cases with NAFLD and controls at borderline significance (median, 76 vs. 83%; P = 0.07). Cases had higher intrahepatic insulin exposure than controls, both in the basal (34 vs. 18 pmol; P = 0.0002) and glucose-stimulated states (58 vs. 24 pmol; P = 0.01). IHCL was significantly related to both basal (r(s) = 0.62; P < 0.0001) and IVGTT intrahepatic insulin exposure (r(s) = 0.47; P = 0.002). As predictors of IHCL, both basal and IVGTT intrahepatic insulin exposure were dependent on the waist-to-hip ratio and homeostasis model assessment insulin resistance, but not on magnetic resonance imaging fat measures or IVGTT insulin sensitivity.
  
  
  CONCLUSIONS
  Men with NAFLD have higher intrahepatic insulin exposure than controls. This correlates with IHCL, but the principal determinants of IHCL were fat distribution and hepatic rather than peripheral insulin resistance.
authors.affiliation: Division of Diabetes Endocrinology and Metabolism, Department of Medicine, Imperial College London, Mary's Hospital, Praed Street, London W2 1NY, United Kingdom. s.mehta@imperial.ac.uk
authors.forename: Sanjeev R
authors.initials: SR
authors.lastname: Mehta
authors.forename: Ian F
authors.initials: IF
authors.lastname: Godsland
authors.forename: E Louise
authors.initials: EL
authors.lastname: Thomas
authors.forename: Darrell V
authors.initials: DV
authors.lastname: Pavitt
authors.forename: Stanislas X
authors.initials: SX
authors.lastname: Morin
authors.forename: Jimmy D
authors.initials: JD
authors.lastname: Bell
authors.forename: Simon D
authors.initials: SD
authors.lastname: Taylor-Robinson
authors.forename: Desmond G
authors.initials: DG
authors.lastname: Johnston
mesh_terms: D000273:Adipose Tissue / Q000502:physiology*; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D015331:Cohort Studies; D005234:Fatty Liver / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin