title: Lower fasting muscle mitochondrial activity relates to hepatic steatosis in humans.
abstract: OBJECTIVE
  Muscle insulin resistance has been implicated in the development of steatosis and dyslipidemia by changing the partitioning of postprandial substrate fluxes. Also, insulin resistance may be due to reduced mitochondrial function. We examined the association between mitochondrial activity, insulin sensitivity, and steatosis in a larger human population.
  
  
  METHODS
  We analyzed muscle mitochondrial activity from ATP synthase flux (fATP) and ectopic lipids by multinuclei magnetic resonance spectroscopy from 113 volunteers with and without diabetes. Insulin sensitivity was assessed from M values using euglycemic-hyperinsulinemic clamps and/or from oral glucose insulin sensitivity (OGIS) using oral glucose tolerance tests.
  
  
  RESULTS
  Muscle fATP correlated negatively with hepatic lipid content and HbA1c. After model adjustment for study effects and other confounders, fATP showed a strong negative correlation with hepatic lipid content and a positive correlation with insulin sensitivity and fasting C-peptide. The negative correlation of muscle fATP with age, HbA1c, and plasma free fatty acids was weakened after adjustment. Body mass, muscle lipid contents, plasma lipoproteins, and triglycerides did not associate with fATP.
  
  
  CONCLUSIONS
  The association of impaired muscle mitochondrial activity with hepatic steatosis supports the concept of a close link between altered muscle and liver energy metabolism as early abnormalities promoting insulin resistance.
authors.affiliation: Corresponding author: Michael Roden, michael.roden@ddz.uni-duesseldorf.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Szendroedi
authors.forename: Kirti
authors.initials: K
authors.lastname: Kaul
authors.forename: Lisa
authors.initials: L
authors.lastname: Kloock
authors.forename: Klaus
authors.initials: K
authors.lastname: Straßburger
authors.forename: Albrecht Ingo
authors.initials: AI
authors.lastname: Schmid
authors.forename: Marek
authors.initials: M
authors.lastname: Chmelik
authors.forename: Michaela
authors.initials: M
authors.lastname: Kacerovsky
authors.forename: Gertrud
authors.initials: G
authors.lastname: Kacerovsky-Bielesz
authors.forename: Thomas
authors.initials: T
authors.lastname: Prikoszovich
authors.forename: Attila
authors.initials: A
authors.lastname: Brehm
authors.forename: Martin
authors.initials: M
authors.lastname: Krssák
authors.forename: Stephan
authors.initials: S
authors.lastname: Gruber
authors.forename: Michael
authors.initials: M
authors.lastname: Krebs
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kautzky-Willer
authors.forename: Ewald
authors.initials: E
authors.lastname: Moser
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D000328:Adult; D005215:Fasting; D005234:Fatty Liver / Q000378:metabolism*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*; D055815:Young Adult
chemical_list: D025261:Mitochondrial Proton-Translocating ATPases