title: Relationship between plasma free fatty acids and uncoupling protein-3 gene expression in skeletal muscle of obese subjects: in vitro evidence of a causal link.
abstract: OBJECTIVE
  To investigate whether skeletal muscle uncoupling protein-2 (UCP2) and uncoupling protein-3 (UCP3) gene expression is altered in massive obesity and whether it correlates with in vivo insulin sensitivity and with metabolic and hormonal status.
  
  
  METHODS
  Quantification of UCP2 and UCP3 gene expression in skeletal muscle of obese and lean subjects displaying different degrees of insulin sensitivity.
  
  
  METHODS
  Fourteen obese and 10 age- and sex-matched healthy control subjects with a mean body mass index (BMI) of 43.6 +/- 1.4 and 22.8 +/- 1.8 (+/- SEM), respectively.
  
  
  METHODS
  Insulin sensitivity by glucose clamp, body composition by bio-impedance, fasting plasma glucose, insulin, leptin and free fatty acids (FFA). Skeletal muscle UCP2 and UCP3 mRNA levels by quantitative reverse transcription polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  No significant differences in UCP2 or UCP3 mRNA levels were found between obese and control subjects. No significant correlation was observed, in both groups, between UCP2 or UCP3 mRNA levels and both anthropometrical and metabolic parameters. In contrast, a highly significant correlation was observed between skeletal muscle UCP3, but not UCP2, mRNA levels and plasma FFA in the obese, but not in the lean, group. Furthermore, exposure of human myocytes to FFA for 24 h strongly induced both UCP3 and peroxisome proliferator-activated receptor-gamma (PPARgamma) but not UCP2 gene expression.
  
  
  CONCLUSIONS
  FFA levels correlate strongly with skeletal muscle UCP3 mRNA levels in obese, but not in lean, subjects; in addition, in human myocytes, high FFA concentrations promote UCP3 expression. Our studies therefore provide evidence that supports a role for increased plasma FFA concentrations in the regulation of human skeletal muscle UCP3 gene expression.
authors.affiliation: Loboratory of Molecular Medicine, Department of Internal Medicine, University of Rome 'Tor Vergata', Italy. sbraccia@med.uniroma2.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Sbraccia
authors.forename: Monica
authors.initials: M
authors.lastname: D'Adamo
authors.forename: Frida
authors.initials: F
authors.lastname: Leonetti
authors.forename: Angela
authors.initials: A
authors.lastname: Buongiorno
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Silecchia
authors.forename: Maria Sole
authors.initials: MS
authors.lastname: Basso
authors.forename: Guido
authors.initials: G
authors.lastname: Tamburrano
authors.forename: Davide
authors.initials: D
authors.lastname: Lauro
authors.forename: Massimo
authors.initials: M
authors.lastname: Federici
authors.forename: Nicola
authors.initials: N
authors.lastname: Di Daniele
authors.forename: Renato
authors.initials: R
authors.lastname: Lauro
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002478:Cells, Cultured; D005230:Fatty Acids, Nonesterified / Q000097:blood* / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood; D007473:Ion Channels; D020738:Leptin / Q000097:blood; D016014:Linear Models; D008297:Male; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000209:etiology* / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000378:metabolism; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007473:Ion Channels; D020738:Leptin; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3