REGULATION OF WHOLE-BODY ENERGY HOMEOSTASIS WITH GROWTH HORMONE REPLACEMENT THERAPY AND ENDURANCE EXERCISE

Oosterhof, Robert; Ith, Michael; Trepp, Roman; Christ, Emanuel R; Flueck, Martin (2011). REGULATION OF WHOLE-BODY ENERGY HOMEOSTASIS WITH GROWTH HORMONE REPLACEMENT THERAPY AND ENDURANCE EXERCISE. Physiological genomics, 43(12), pp. 739-48. Bethesda, Md.: American Physiological Society 10.1152/physiolgenomics.00034.2010

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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 (| r | ≥ 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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic, Interventional and Paediatric Radiology > DCR Magnetic Resonance Spectroscopy and Methodology (AMSM) 04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Endocrinology, Diabetology and Clinical Nutrition
UniBE Contributor:	Ith, Michael, Trepp, Roman, Christ, Emanuel
ISSN:	1094-8341
Publisher:	American Physiological Society
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:10
Last Modified:	02 Mar 2023 23:20
Publisher DOI:	10.1152/physiolgenomics.00034.2010
PubMed ID:	21447747
Web of Science ID:	000292136200003
URI:	https://boris.unibe.ch/id/eprint/1327 (FactScience: 202730)