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

Arch. Biochem. Biophys. 589, 93-107 (2015)
Postprint DOI
Open Access Green
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 and which is strongly regulated during adipogenesis. In addition, propionyl-CoA, a product of isoleucine degradation, was identified as a putative substrate for odd chain fatty acid synthesis. The uncovered crosstalk's between BCAA and lipid metabolism during adipogenesis might contribute to the understanding of molecular mechanisms of obesity and have potential implications in obesity prediction.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Adipogenesis ; Branched Chain Amino Acids ; Fatty Acids ; Glycerophospholipids ; Metabolic Pathways ; Metabolomics ; Obesity ; Phosphatidylcholines
ISSN (print) / ISBN 0003-9861
e-ISSN 1096-0384
Quellenangaben Volume: 589, Issue: , Pages: 93-107 Article Number: , Supplement: ,
Publisher Elsevier
Reviewing status Peer reviewed
Institute(s) Molekulare Endokrinologie und Metabolismus (MEM)
Institute of Experimental Genetics (IEG)
Institute of Bioinformatics and Systems Biology (IBIS)
CCG Nutrigenomics and Type 2 Diabetes (KKG-KDN)