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


Oosterhof, Robert; Ith, Michael; Trepp, Roman; Christ, Emanuel; Flück, Martin (2011). Regulation of whole body energy homeostasis with growth hormone replacement therapy and endurance exercise. Physiological Genomics, 43(12):739-748.

Abstract

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.

Abstract

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.

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4 citations in Web of Science®
5 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Balgrist University Hospital, Swiss Spinal Cord Injury Center
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:28 June 2011
Deposited On:06 Aug 2015 06:47
Last Modified:05 Apr 2016 19:20
Publisher:American Physiological Society
ISSN:1094-8341
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1152/physiolgenomics.00034.2010
PubMed ID:21447747

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