title: Relationship between adipose tissue lipolytic activity and skeletal muscle insulin resistance in nondiabetic women.
abstract: BACKGROUND
  Increased adipose tissue lipolytic activity is considered an important factor in the pathogenesis of skeletal muscle insulin resistance associated with obesity.
  
  
  OBJECTIVE
  The objective of the study was to evaluate the relationship between the rate of release of free fatty acids (FFA) into plasma and skeletal muscle insulin sensitivity in human subjects.
  
  
  METHODS
  We determined the palmitate rate of appearance (Ra) per kilogram fat-free mass (an index of FFA availability to lean tissues) during basal conditions and during insulin infusion (to simulate postprandial insulin concentrations) and skeletal muscle insulin sensitivity, defined as the percent increase in the glucose rate of disappearance, in 110 nondiabetic women (body mass index 20.6-46.4 kg/m(2)) by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope tracer methods.
  
  
  RESULTS
  Basal (r(s) = -0.379, P < 0.001) and insulin-suppressed (r(s) = -0.631, P < 0.001) palmitate Ra correlated negatively with skeletal muscle insulin sensitivity. However, the strength of the correlation was greater for palmitate Ra during insulin infusion than palmitate Ra during basal conditions (P = 0.0007) when lipolytic rates and FFA availability were reduced to less than 20% of basal values. The relative suppression of palmitate Ra correlated directly with the relative stimulation of glucose rate of disappearance during insulin infusion (r(s) = 0.530, P < 0.001).
  
  
  CONCLUSIONS
  These data suggest that the correlation between FFA kinetics and muscle glucose metabolism is due to multiorgan insulin resistance rather than a direct effect of FFA itself on skeletal muscle insulin action and challenge the view that increased adipose tissue lipolytic rate is an important cause of insulin resistance.
authors.affiliation: Center for Human Nutrition, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8031, St. Louis, Missouri 63110, USA.
authors.forename: Faidon
authors.initials: F
authors.lastname: Magkos
authors.forename: Elisa
authors.initials: E
authors.lastname: Fabbrini
authors.forename: Caterina
authors.initials: C
authors.lastname: Conte
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Patterson
authors.forename: Samuel
authors.initials: S
authors.lastname: Klein
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D000368:Aged; D003920:Diabetes Mellitus / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D019308:Palmitic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D011849:Radioactive Tracers; D055815:Young Adult
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D011849:Radioactive Tracers; D019308:Palmitic Acid