title: Influence of age on leptin induced skeletal muscle signalling.
abstract: OBJECTIVE
  Age associated fat mass accumulation could be because of dysregulation of leptin signalling in skeletal muscle. Thus, we investigated total protein expression and phosphorylation levels of the long isoform of the leptin receptor (OB-Rb), and leptin signalling through janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3), insulin receptor substrate 1 (IRS-1), AMP-activated protein kinase (AMPK) and acetyl-coenzyme A carboxylase (ACC), combined with the leptin signalling inhibitors suppressor of cytokine signalling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) in human skeletal muscle of different age.
  
  
  METHODS
  Vastus lateralis muscle biopsies were obtained from 39 men matched for BMI < 30 kg m(-2) and separated into three groups: 13 young (Y, 24 ± 4 years); 14 middle aged (MA, 44 ± 5 years) and 12 aged (A, 58 ± 8 years) subjects.
  
  
  RESULTS
  Whole body fat percentage and plasma leptin were higher (P < 0.05), whereas lean mass, plasma free testosterone and total testosterone were lower (P < 0.05) in A compared to Y. Skeletal muscle OB-Rb (170 KDa) protein expression and pTyr(1141) -OB-R170 were comparable between groups, whereas pTyr(985) -OB-R170 was lower in A compared to Y (P < 0.05). pSTAT3 levels tended (P = 0.09) to be lower (50%) in A compared to Y. In A, muscle PTP1B was greater and IRS-1 lower than Y and MA respectively (P < 0.05). PTyr(612) -IRS-1 tended to be lower in A than in Y (P = 0.09). Suppressor of cytokine signalling 3 (SOCS3) protein expression, pJAK2, pSer(1101) -IRS-1, pAMPKα and pACCβ were similar between groups.
  
  
  CONCLUSIONS
  Age is associated with dysregulation of the leptin signalling and increased PTP1B protein expression in skeletal muscle.
authors.affiliation: Department of Physical Education, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain; Xlab, Department of Biomedical Sciences, Faculty of Health Sciences, Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Guadalupe-Grau
authors.forename: S
authors.initials: S
authors.lastname: Larsen
authors.forename: B
authors.initials: B
authors.lastname: Guerra
authors.forename: J A L
authors.initials: JA
authors.lastname: Calbet
authors.forename: F
authors.initials: F
authors.lastname: Dela
authors.forename: J W
authors.initials: JW
authors.lastname: Helge
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000328:Adult; D000367:Age Factors; D000368:Aged; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D054411:Receptors, Leptin / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D020738:Leptin; D054411:Receptors, Leptin; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D000263:Adenylate Kinase
keywords: age; androgens; insulin receptor substrate 1; leptin resistance; protein tyrosine phosphatase 1B; skeletal muscle