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Review
. 2018 Jul 5:13:17.
doi: 10.1186/s12263-018-0609-3. eCollection 2018.

Exploring the cellular network of metabolic flexibility in the adipose tissue

Samar H K Tareen  1 , Martina Kutmon  1   2 , Michiel E Adriaens  1 , Edwin C M Mariman  3 , Theo M de Kok  1   4 , Ilja C W Arts  1   5 , Chris T Evelo  1   2
Affiliations
Review

Exploring the cellular network of metabolic flexibility in the adipose tissue

Samar H K Tareen et al. Genes Nutr. .

Abstract

Background: Metabolic flexibility is the ability of cells to change substrates for energy production based on the nutrient availability and energy requirement. It has been shown that metabolic flexibility is impaired in obesity and chronic diseases such as type 2 diabetes mellitus, cardiovascular diseases, and metabolic syndrome, although, whether it is a cause or an effect of these conditions remains to be elucidated.

Main body: In this paper, we have reviewed the literature on metabolic flexibility and curated pathways and processes resulting in a network resource to investigate the interplay between these processes in the subcutaneous adipose tissue. The adipose tissue has been shown to be responsible, not only for energy storage but also for maintaining energy homeostasis through oxidation of glucose and fatty acids. We highlight the role of pyruvate dehydrogenase complex-pyruvate dehydrogenase kinase (PDC-PDK) interaction as a regulatory switch which is primarily responsible for changing substrates in energy metabolism from glucose to fatty acids and back. Baseline gene expression of the subcutaneous adipose tissue, along with a publicly available obesity data set, are visualised on the cellular network of metabolic flexibility to highlight the genes that are expressed and which are differentially affected in obesity.

Conclusion: We have constructed an abstracted network covering glucose and fatty acid oxidation, as well as the PDC-PDK regulatory switch. In addition, we have shown how the network can be used for data visualisation and as a resource for follow-up studies.

Keywords: Metabolic flexibility; Metabolism; Networks; Obesity; Pathways; Regulation.

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Conflict of interest statement

Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Methodology overview showing the workflow to construct the abstracted network. (i) Known knowledge in the form of published literature and databases is queried regarding cellular metabolism. (ii) Base biological processes are isolated and then expanded by adding regulators and other related processes as long as they are related to cellular metabolism. (iii) The expanded network is then abstracted by merging edges such that only major components and rate-limiting steps remain
Fig. 2
Fig. 2
Abstracted cellular network of metabolic flexibility in the adipose tissue. The network consists of different pathways and processes, which are grouped together into five major, colour-coded categories: (i) green for glycolysis, (ii) orange for fatty acid β-oxidation, (iii) yellow for fatty acid synthesis, (iv) cyan for TCA cycle and (v) magenta for regulators of metabolic flexibility
Fig. 3
Fig. 3
Baseline gene expression of the network in the adipose tissue. Expression is median log2 TPM expression of GTEx Homo sapiens baseline dataset from Expression Atlas
Fig. 4
Fig. 4
Differential expression of the metabolic flexibility network between obese vs lean healthy individuals. Data shown is GSE55200 from the gene expression omnibus. FC means fold change
See this image and copyright information in PMC

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