Influence of age on leptin induced skeletal muscle signalling

Abstract

Aim:Age associated fat mass accumulation could be because of dysregula-tion of leptin signalling in skeletal muscle. Thus, we investigated total pro-tein expression and phosphorylation levels of the long isoform of theleptin receptor (OB-Rb), and leptin signalling through janus kinase 2(JAK2)/signal transducer and activator of transcription 3 (STAT3), insulinreceptor substrate 1 (IRS-1), AMP-activated protein kinase (AMPK) andacetyl-coenzyme A carboxylase (ACC), combined with the leptin signallinginhibitors suppressor of cytokine signalling 3 (SOCS3) and protein tyrosinephosphatase 1B (PTP1B) in human skeletal muscle of different age.Methods:Vastus lateralis muscle biopsies were obtained from 39 menmatched for BMI<30 kg m 2and 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 testoster-one were lower (P<0.05) in A compared to Y. Skeletal muscle OB-Rb(170 KDa) protein expression and pTyr1141-OB-R170 were comparablebetween groups, whereas pTyr985-OB-R170 was lower in A compared toY(P<0.05). pSTAT3 levels tended (P=0.09) to be lower (50%) in Acompared to Y. In A, muscle PTP1B was greater and IRS-1 lower than Yand MA respectively (P<0.05). PTyr612-IRS-1 tended to be lower in Athan in Y (P=0.09). Suppressor of cytokine signalling 3 (SOCS3) proteinexpression, pJAK2, pSer1101-IRS-1, pAMPKaand pACCbwere similarbetween groups.Conclusion:Age is associated with dysregulation of the leptin signallingand increased PTP1B protein expression in skeletal muscle.Keywordsage, leptin resistance, androgens, insulin receptor substrate 1,protein tyrosine phosphatase 1B, skeletal muscle.