Influence of age on leptin induced skeletal muscle signalling

Abstract

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. 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. 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. Age is associated with dysregulation of the leptin signalling and increased PTP1B protein expression in skeletal muscle.