Metabolic switch during adipogenesis

From branched chain amino acid catabolism to lipid synthesis

Anna Halama, Marion Horsch, Gabriele Kastenmüller, Gabriele Möller, Pankaj Kumar, Cornelia Prehn, Helmut Laumen, Hans Hauner, Martin Hrabě De Angelis, Johannes Beckers, Karsten Suhre, Jerzy Adamski

Research output: Contribution to journalReview article

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)93-107
Number of pages15
JournalArchives of Biochemistry and Biophysics
Volume589
DOIs
Publication statusPublished - 1 Jan 2016
Externally publishedYes

Fingerprint

Adipogenesis
Branched Chain Amino Acids
Metabolism
Switches
Adipocytes
Lipids
Isoleucine
Fats
Leucine
Enoyl-CoA Hydratase
Fatty Acids
Obesity
Degradation
RNA-Binding Proteins
Valine
Metabolites
Crosstalk
Phosphatidylcholines
Pharmaceutical Preparations
Drug Repositioning

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Metabolic switch during adipogenesis : From branched chain amino acid catabolism to lipid synthesis. / Halama, Anna; Horsch, Marion; Kastenmüller, Gabriele; Möller, Gabriele; Kumar, Pankaj; Prehn, Cornelia; Laumen, Helmut; Hauner, Hans; Hrabě De Angelis, Martin; Beckers, Johannes; Suhre, Karsten; Adamski, Jerzy.

In: Archives of Biochemistry and Biophysics, Vol. 589, 01.01.2016, p. 93-107.

Research output: Contribution to journalReview article

Halama, A, Horsch, M, Kastenmüller, G, Möller, G, Kumar, P, Prehn, C, Laumen, H, Hauner, H, Hrabě De Angelis, M, Beckers, J, Suhre, K & Adamski, J 2016, 'Metabolic switch during adipogenesis: From branched chain amino acid catabolism to lipid synthesis', Archives of Biochemistry and Biophysics, vol. 589, pp. 93-107. https://doi.org/10.1016/j.abb.2015.09.013
Halama, Anna ; Horsch, Marion ; Kastenmüller, Gabriele ; Möller, Gabriele ; Kumar, Pankaj ; Prehn, Cornelia ; Laumen, Helmut ; Hauner, Hans ; Hrabě De Angelis, Martin ; Beckers, Johannes ; Suhre, Karsten ; Adamski, Jerzy. / Metabolic switch during adipogenesis : From branched chain amino acid catabolism to lipid synthesis. In: Archives of Biochemistry and Biophysics. 2016 ; Vol. 589. pp. 93-107.
@article{b069186946e1477596de9f72b74d7469,
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.",
keywords = "Adipogenesis, Branched chain amino acids, Fatty acids, Glycerophospholipids, Metabolic pathways, Metabolomics, Obesity, Phosphatidylcholines",
author = "Anna Halama and Marion Horsch and Gabriele Kastenm{\"u}ller and Gabriele M{\"o}ller and Pankaj Kumar and Cornelia Prehn and Helmut Laumen and Hans Hauner and {Hrabě De Angelis}, Martin and Johannes Beckers and Karsten Suhre and Jerzy Adamski",
year = "2016",
month = "1",
day = "1",
doi = "10.1016/j.abb.2015.09.013",
language = "English",
volume = "589",
pages = "93--107",
journal = "Archives of Biochemistry and Biophysics",
issn = "0003-9861",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Metabolic switch during adipogenesis

T2 - From branched chain amino acid catabolism to lipid synthesis

AU - Halama, Anna

AU - Horsch, Marion

AU - Kastenmüller, Gabriele

AU - Möller, Gabriele

AU - Kumar, Pankaj

AU - Prehn, Cornelia

AU - Laumen, Helmut

AU - Hauner, Hans

AU - Hrabě De Angelis, Martin

AU - Beckers, Johannes

AU - Suhre, Karsten

AU - Adamski, Jerzy

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

KW - Adipogenesis

KW - Branched chain amino acids

KW - Fatty acids

KW - Glycerophospholipids

KW - Metabolic pathways

KW - Metabolomics

KW - Obesity

KW - Phosphatidylcholines

UR - http://www.scopus.com/inward/record.url?scp=84950335546&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84950335546&partnerID=8YFLogxK

U2 - 10.1016/j.abb.2015.09.013

DO - 10.1016/j.abb.2015.09.013

M3 - Review article

VL - 589

SP - 93

EP - 107

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

SN - 0003-9861

ER -