Influence of age on leptin induced skeletal muscle signaling

TY - JOUR

T1 - Influence of age on leptin induced skeletal muscle signaling

AU - Guadalupe Grau, Amelia

AU - Larsen, Steen

AU - Guerra, Borja

AU - Calbet, Jose Al

AU - Dela, Flemming

AU - Helge, Jørn Wulff

N1 - This article is protected by copyright. All rights reserved.

PY - 2014/5

Y1 - 2014/5

N2 - Aim: 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 pTyr1141-OB-R170 were comparable between groups, whereas pTyr985-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). PTyr612-IRS-1 tended to be lower in A than in Y (P = 0.09). Suppressor of cytokine signalling 3 (SOCS3) protein expression, pJAK2, pSer1101-IRS-1, pAMPKα and pACCβ were similar between groups. Conclusion: Age is associated with dysregulation of the leptin signalling and increased PTP1B protein expression in skeletal muscle.

AB - Aim: 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 pTyr1141-OB-R170 were comparable between groups, whereas pTyr985-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). PTyr612-IRS-1 tended to be lower in A than in Y (P = 0.09). Suppressor of cytokine signalling 3 (SOCS3) protein expression, pJAK2, pSer1101-IRS-1, pAMPKα and pACCβ were similar between groups. Conclusion: Age is associated with dysregulation of the leptin signalling and increased PTP1B protein expression in skeletal muscle.

U2 - 10.1111/apha.12273

DO - 10.1111/apha.12273

M3 - Journal article

C2 - 24605926

SN - 1748-1708

VL - 211

SP - 214

EP - 228

JO - Acta Physiologica

JF - Acta Physiologica

IS - 1

ER -