Leptin signaling in skeletal muscle after bed rest in healthy humans

PURPOSE: This study aimed at determining the effects of bed rest on the skeletal muscle leptin signaling system.

METHODS: Deltoid and vastus lateralis muscle biopsies and blood samples were obtained from 12 healthy young men (mean ± SD, BMI 22.8 ± 2.7 kg/m(2)) before and after 7 days of bed rest. Leptin receptor isoforms (OB-Rs), suppressor of cytokine signaling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) protein expression and signal transducer and activator of transcription 3 (STAT3) phosphorylation were analyzed by Western blot.

RESULTS: After bed rest basal insulin concentration was increased by 53% (P < 0.05), the homeostasis model assessment (HOMA) by 40% (P < 0.05), and serum leptin concentration by 35% (P < 0.05) with no changes in body fat mass. Although the soluble isoform of the leptin receptor (s-OBR) remained unchanged, the molar excess of leptin over sOB-R was increased by 1.4-fold after bed rest (P < 0.05). OB-Rs and SOCS3 protein expression, and STAT3 phosphorylation level remained unaffected in deltoid and vastus lateralis by bed rest, as PTP1B in the deltoid. PTP1B was increased by 90% with bed rest in the vastus lateralis (P < 0.05). There was a linear relationship between the increase in vastus lateralis PTP1B and the increase in both basal insulin concentrations (r = 0.66, P < 0.05) and HOMA (r = 0.68, P < 0.05) with bed rest.

CONCLUSIONS: One week of bed rest is associated with increased leptin levels without augmenting STAT3 phosphorylation indicating some degree of leptin resistance in skeletal muscle, which can be explained, at least in part, by an elevation of PTP1B protein content in the vastus lateralis muscle.