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Arch Biochem Biophys. 2016 Jan 1;589:93-107. doi: 10.1016/j.abb.2015.09.013. Epub 2015 Sep 25.

Metabolic switch during adipogenesis: From branched chain amino acid catabolism to lipid synthesis.

Author information

1
Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Department of Physiology and Biophysics, Weill Cornell Medical College - Qatar, Doha, Qatar.
2
Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
3
Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
4
Department of Physiology and Biophysics, Weill Cornell Medical College - Qatar, Doha, Qatar.
5
Else Kröner-Fresenius-Centre for Nutritional Medicine, Klinikum Rechts der Isar, Technical University München, München, Germany.
6
Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research, Neuherberg, Germany; Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany.
7
Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research, Neuherberg, Germany; Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany. Electronic address: adamski@helmholtz-muenchen.de.

Abstract

Fat cell metabolism has an impact on body homeostasis and its proper function. Nevertheless, the knowledge about simultaneous metabolic processes, which occur during adipogenesis and in mature adipocytes, is limited. Identification of key metabolic events associated with fat cell metabolism could be beneficial in the field of novel drug development, drug repurposing, as well as for the discovery of patterns predicting obesity risk. The main objective of our work was to provide comprehensive characterization of metabolic processes occurring during adipogenesis and in mature adipocytes. In order to globally determine crucial metabolic pathways involved in fat cell metabolism, metabolomics and transcriptomics approaches were applied. We observed significantly regulated metabolites correlating with significantly regulated genes at different stages of adipogenesis. We identified the synthesis of phosphatidylcholines, the metabolism of even and odd chain fatty acids, as well as the catabolism of branched chain amino acids (BCAA; leucine, isoleucine and valine) as key regulated pathways. Our further analysis led to identification of an enzymatic switch comprising the enzymes Hmgcs2 (3-hydroxy-3-methylglutaryl-CoA synthase) and Auh (AU RNA binding protein/enoyl-CoA hydratase) which connects leucine degradation with cholesterol synthesis. In addition, propionyl-CoA, a product of isoleucine degradation, was identified as a putative substrate for odd chain fatty acid synthesis. The uncovered crosstalks between BCAA and lipid metabolism during adipogenesis might contribute to the understanding of molecular mechanisms of obesity and have potential implications in obesity prediction.

KEYWORDS:

Adipogenesis; Branched chain amino acids; Fatty acids; Glycerophospholipids; Metabolic pathways; Metabolomics; Obesity; Phosphatidylcholines

PMID:
26408941
DOI:
10.1016/j.abb.2015.09.013
[Indexed for MEDLINE]

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