title: Metabolic inflexibility and insulin resistance in obese adolescents with non-alcoholic fatty liver disease.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) is a comorbidity of childhood obesity.
  
  
  OBJECTIVE
  We examined whole-body substrate metabolism and metabolic characteristics in obese adolescents with vs. without NAFLD.
  
  
  METHODS
  Twelve obese (BMI ≥ 95th percentile) adolescents with and without NAFLD [intrahepatic triglyceride (IHTG) ≥5.0% vs. <5.0%] were pair-matched for race, gender, age and % body fat.
  
  
  METHODS
  Insulin sensitivity (IS) was assessed by a 3-h hyperinsulinemic-euglycemic clamp and whole-body substrate oxidation by indirect calorimetry during fasting and insulin-stimulated conditions.
  
  
  RESULTS
  Adolescents with NAFLD had increased (p < 0.05) abdominal fat, lipids, and liver enzymes compared with those without NAFLD. Fasting glucose concentration was not different between groups, but fasting insulin concentration was higher (p < 0.05) in the NAFLD group compared with those without. Fasting hepatic glucose production and hepatic IS did not differ (p > 0.1) between groups. Adolescents with NAFLD had higher (p < 0.05) fasting glucose oxidation and a tendency for lower fat oxidation. Adolescents with NAFLD had lower (p < 0.05) insulin-stimulated glucose disposal and lower peripheral IS compared with those without NAFLD. Although respiratory quotient (RQ) increased significantly from fasting to insulin-stimulated conditions in both groups (main effect, p < 0.001), the increase in RQ was lower in adolescents with NAFLD vs. those without (interaction, p = 0.037).
  
  
  CONCLUSIONS
  NAFLD in obese adolescents is associated with adverse cardiometabolic profile, peripheral insulin resistance and metabolic inflexibility.
authors.affiliation: Division of Weight Management and Wellness, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: SoJung
authors.initials: S
authors.lastname: Lee
authors.forename: Michelle
authors.initials: M
authors.lastname: Rivera-Vega
authors.forename: Hany Mohamed Abdel Aal
authors.initials: HM
authors.lastname: Alsayed
authors.forename: Chris
authors.initials: C
authors.lastname: Boesch
authors.forename: Ingrid
authors.initials: I
authors.lastname: Libman
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D004734:Energy Metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000378:metabolism*; D009765:Obesity / Q000150:complications*
chemical_list: D005947:Glucose
keywords: childhood obesity; insulin sensitivity; non-alcoholic fatty liver disease; visceral fat
references.citation: Diabetes Care. 1995 Feb;18(2):245-50
references.pmid: 7729306
references.citation: J Obes. 2011;2011:159373
references.pmid: 21772999
references.citation: N Engl J Med. 1990 Jan 25;322(4):223-8
references.pmid: 2403659
references.citation: Liver Int. 2009 Oct;29(9):1439-46
references.pmid: 19602132
references.citation: Pediatrics. 2006 Oct;118(4):1388-93
references.pmid: 17015527
references.citation: Diabetes Care. 2003 Jan;26 Suppl 1:S5-20
references.pmid: 12502614
references.citation: Am J Physiol Endocrinol Metab. 2013 Nov 15;305(10):E1222-9
references.pmid: 24045865
references.citation: J Pediatr. 2012 Jul;161(1):51-7
references.pmid: 22325254
references.citation: Adv Pediatr. 2010;57(1):85-140
references.pmid: 21056736
references.citation: Am J Physiol. 1990 Nov;259(5 Pt 1):E650-7
references.pmid: 2240203
references.citation: MAGMA. 2001 May;12(2-3):141-52
references.pmid: 11390270
references.citation: Diabetes. 2000 May;49(5):677-83
references.pmid: 10905472
references.citation: Gastroenterology. 2001 Apr;120(5):1183-92
references.pmid: 11266382
references.citation: Diabetes. 2012 Nov;61(11):2787-95
references.pmid: 22751691
references.citation: Hepatology. 2009 Jun;49(6):1896-903
references.pmid: 19434725
references.citation: Hepatology. 2004 Dec;40(6):1387-95
references.pmid: 15565570
references.citation: J Clin Invest. 1994 Dec;94(6):2349-56
references.pmid: 7989591
references.citation: Am J Physiol. 1999 Dec;277(6):E1130-41
references.pmid: 10600804
references.citation: J Clin Invest. 1976 Aug;58(2):421-31
references.pmid: 956375
references.citation: Diabetes. 2003 Sep;52(9):2191-7
references.pmid: 12941756
references.citation: Gut. 2013 Nov;62(11):1625-33
references.pmid: 23077135
references.citation: Obesity (Silver Spring). 2012 Feb;20(2):371-5
references.pmid: 21869763
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12587-94
references.pmid: 17640906
references.citation: Nutrition. 2012 Jul;28(7-8):722-6
references.pmid: 22464551
references.citation: Diabetes Care. 2012 Apr;35(4):905-10
references.pmid: 22357180
references.citation: J Appl Physiol Respir Environ Exerc Physiol. 1983 Aug;55(2):628-34
references.pmid: 6618956
references.citation: Obesity (Silver Spring). 2012 May;20(5):1034-40
references.pmid: 22222927
references.citation: Diabetologia. 2005 Apr;48(4):634-42
references.pmid: 15747110
references.citation: Hepatology. 2003 Apr;37(4):917-23
references.pmid: 12668987
references.citation: Am J Physiol Endocrinol Metab. 2006 Oct;291(4):E697-703
references.pmid: 16684857
references.citation: Diabetes Care. 2004 Feb;27(2):547-52
references.pmid: 14747242
references.citation: Obesity (Silver Spring). 2009 Sep;17(9):1744-8
references.pmid: 19498349
references.citation: Am J Clin Nutr. 2008 Aug;88(2):257-62
references.pmid: 18689359