title: Time course of postprandial hepatic phosphorus metabolites in lean, obese, and type 2 diabetes patients.
abstract: BACKGROUND
  Impaired energy metabolism is a possible mechanism that contributes to insulin resistance and ectopic fat storage.
  
  
  OBJECTIVE
  We examined whether meal ingestion differently affects hepatic phosphorus metabolites in insulin-sensitive and insulin-resistant humans.
  
  
  METHODS
  Young, lean, insulin-sensitive humans (CONs) [mean ± SD body mass index (BMI; in kg/m(2)): 23.2 ± 1.5]; insulin-resistant, glucose-tolerant, obese humans (OBEs) (BMI: 34.3 ± 1.7); and type 2 diabetes patients (T2Ds) (BMI: 32.0 ± 2.4) were studied (n = 10/group). T2Ds (61 ± 7 y old) were older (P < 0.001) than were OBEs (31 ± 7 y old) and CONs (28 ± 3 y old). We quantified hepatic γATP, inorganic phosphate (Pi), and the fat content [hepatocellular lipids (HCLs)] with the use of (31)P/(1)H magnetic resonance spectroscopy before and at 160 and 240 min after a high-caloric mixed meal. In a subset of volunteers, we measured the skeletal muscle oxidative capacity with the use of high-resolution respirometry. Whole-body insulin sensitivity (M value) was assessed with the use of hyperinsulinemic-euglycemic clamps.
  
  
  RESULTS
  OBEs and T2Ds were similarly insulin resistant (M value: 3.5 ± 1.4 and 1.9 ± 2.5 mg · kg(-1) · min(-1), respectively; P = 0.9) and had 12-fold (P = 0.01) and 17-fold (P = 0.002) higher HCLs, respectively, than those of lean persons. Despite comparable fasting hepatic γATP concentrations, the maximum postprandial increase of γATP was 6-fold higher in OBEs (0.7 ± 0.2 mmol/L; P = 0.03) but only tended to be higher in T2Ds (0.6 ± 0.2 mmol/L; P = 0.09) than in CONs (0.1 ± 0.1 mmol/L). However, in the fasted state, muscle complex I activity was 53% lower (P = 0.01) in T2Ds but not in OBEs (P = 0.15) than in CONs.
  
  
  CONCLUSIONS
  Young, obese, nondiabetic humans exhibit augmented postprandial hepatic energy metabolism, whereas elderly T2Ds have impaired fasting muscle energy metabolism. These findings support the concept of a differential and tissue-specific regulation of energy metabolism, which can occur independently of insulin resistance. This trial was registered at clinicaltrials.gov as NCT01229059.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Department of Pediatric and Adolescent Medicine, Medical University of Vienna, Vienna, Austria; and.
authors.forename: Maria
authors.initials: M
authors.lastname: Fritsch
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Department of Endocrinology and Diabetology, Medical Faculty, and German Center of Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Chrysi
authors.initials: C
authors.lastname: Koliaki
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research.
authors.forename: Roshan
authors.initials: R
authors.lastname: Livingstone
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research.
authors.forename: Esther
authors.initials: E
authors.lastname: Phielix
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, German Center of Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bierwagen
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research.
authors.forename: Markus
authors.initials: M
authors.lastname: Meisinger
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, German Center of Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Tomas
authors.initials: T
authors.lastname: Jelenik
authors.affiliation: Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany, German Center of Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Strassburger
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, German Center of Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Zimmermann
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, German Center of Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Brockmann
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, German Center of Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Wolff
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, German Center of Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Jong-Hee
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Department of Endocrinology and Diabetology, Medical Faculty, and German Center of Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Szendroedi
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Department of Endocrinology and Diabetology, Medical Faculty, and German Center of Diabetes Research, Partner Düsseldorf, Germany michael.roden@ddz.uni-duesseldorf.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D000368:Aged; D052636:Allostasis; D001706:Biopsy; D015992:Body Mass Index; D002153:Calorimetry, Indirect; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D042967:Electron Transport Complex I / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D019518:Postprandial Period; D052097:Quadriceps Muscle / Q000201:enzymology / Q000378:metabolism / Q000473:pathology
chemical_list: D000255:Adenosine Triphosphate; D042967:Electron Transport Complex I
keywords: hepatic steatosis; mitochondrial function; mixed-meal test; phosphorus magnetic resonance spectroscopy; type 2 diabetes