Regulation of whole body energy homeostasis with growth hormone replacement therapy and endurance exercise

被引:7
作者
Oosterhof, Robert [1 ]
Ith, Michael [2 ]
Trepp, Roman [3 ]
Christ, Emanuel [3 ]
Flueck, Martin [1 ]
机构
[1] Manchester Metropolitan Univ, Inst Biomed Res Human Movement & Hlth, Manchester M1 5GD, Lancs, England
[2] Univ Bern, Dept Clin Res Magnet Resonance Spect & Methodol, Bern, Switzerland
[3] Univ Hosp Bern, Inselspital, Div Endocrinol Diabetol & Clin Nutr, CH-3010 Bern, Switzerland
基金
瑞士国家科学基金会;
关键词
system physiology; molecular; metabolism; network; RESTING METABOLIC-RATE; SKELETAL-MUSCLE; SYSTEMS BIOLOGY; ADIPOSE-TISSUE; RESPIRATORY SYSTEM; PROTEIN-METABOLISM; AEROBIC CAPACITY; LIPID-METABOLISM; DESIGN; SYMMORPHOSIS;
D O I
10.1152/physiolgenomics.00034.2010
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Oosterhof R, Ith M, Trepp R, Christ E, Fluck M. Regulation of whole body energy homeostasis with growth hormone replacement therapy and endurance exercise. Physiol Genomics 43: 739-748, 2011. First published March 29, 2011; doi:10.1152/physiolgenomics.00034.2010.-We hypothesized that network analysis is useful to expose coordination between whole body and myocellular levels of energy metabolism and can identify entities that underlie skeletal muscle's contribution to growth hormone-stimulated lipid handling and metabolic fitness. We assessed 112 metabolic parameters characterizing metabolic rate and substrate handling in tibialis anterior muscle and vascular compartment at rest, after a meal and exercise with growth hormone replacement therapy (GH-RT) of hypopituitary patients (n = 11). The topology of linear relationships (vertical bar r vertical bar >= 0.7, P <= 0.01) and mutual dependencies exposed the organization of metabolic relationships in three entities reflecting basal and exercise-induced metabolic rate, triglyceride handling, and substrate utilization in the pre- and postprandial state, respectively. GH-RT improved aerobic performance (+5%), lean-to-fat mass (+19%), and muscle area of tibialis anterior (+2%) but did not alter its mitochondrial and capillary content. Concomitantly, connectivity was established between myocellular parameters of mitochondrial lipid metabolism and meal-induced triglyceride handling in serum. This was mediated via the recruitment of transcripts of muscle lipid mobilization (LIPE, FABP3, and FABP4) and fatty acid-sensitive transcription factors (PPARA, PPARG) to the metabolic network. The interdependence of gene regulatory elements of muscle lipid metabolism reflected the norm in healthy subjects (n = 12) and distinguished the regulation of the mitochondrial respiration factor COX1 by GH and endurance exercise. Our observations validate the use of network analysis for systems medicine and highlight the notion that an improved stochiometry between muscle and whole body lipid metabolism, rather than alterations of single bottlenecks, contributes to GH-driven elevations in metabolic fitness.
引用
收藏
页码:739 / 748
页数:10
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