title: Metabolic switch during adipogenesis: From branched chain amino acid catabolism to lipid synthesis.
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.
authors.affiliation: 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.
authors.forename: Anna
authors.initials: A
authors.lastname: Halama
authors.affiliation: Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Horsch
authors.affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Kastenmüller
authors.affiliation: Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Möller
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College - Qatar, Doha, Qatar.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Prehn
authors.affiliation: Else Kröner-Fresenius-Centre for Nutritional Medicine, Klinikum Rechts der Isar, Technical University München, München, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Laumen
authors.affiliation: Else Kröner-Fresenius-Centre for Nutritional Medicine, Klinikum Rechts der Isar, Technical University München, München, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Hauner
authors.affiliation: 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.
authors.forename: Martin
authors.initials: M
authors.lastname: Hrabĕ de Angelis
authors.affiliation: 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.
authors.forename: Johannes
authors.initials: J
authors.lastname: Beckers
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College - Qatar, Doha, Qatar.
authors.forename: Karsten
authors.initials: K
authors.lastname: Suhre
authors.affiliation: 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.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis; D000597:Amino Acids, Branched-Chain; D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis; D005227:Fatty Acids / Q000096:biosynthesis / Q000737:chemistry; D020869:Gene Expression Profiling; D008055:Lipids / Q000096:biosynthesis*; D055432:Metabolomics; D051379:Mice
chemical_list: D000597:Amino Acids, Branched-Chain; D005227:Fatty Acids; D008055:Lipids; D002784:Cholesterol
keywords: Adipogenesis; Branched chain amino acids; Fatty acids; Glycerophospholipids; Metabolic pathways; Metabolomics; Obesity; Phosphatidylcholines