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Transcriptome and fatty-acid signatures of adipocyte hypertrophy and its non-invasive MR-based characterization in human adipose tissue.
Honecker, Julius; Ruschke, Stefan; Seeliger, Claudine; Laber, Samantha; Strobel, Sophie; Pröll, Priska; Nellaker, Christoffer; Lindgren, Cecilia M; Kulozik, Ulrich; Ecker, Josef; Karampinos, Dimitrios C; Claussnitzer, Melina; Hauner, Hans.
Affiliation
  • Honecker J; Else Kröner-Fresenius-Center for Nutritional Medicine, Chair of Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Gregor-Mendel-Straße 2, 85354 Freising-Weihenstephan, Germany. Electronic address: julius.honecker@tum.de.
  • Ruschke S; Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Munich, Germany.
  • Seeliger C; Else Kröner-Fresenius-Center for Nutritional Medicine, Chair of Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Gregor-Mendel-Straße 2, 85354 Freising-Weihenstephan, Germany.
  • Laber S; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Strobel S; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Pröll P; Food- and Bioprocess Engineering, TUM School of Life Sciences, Technical University of Munich, Weihenstephaner Berg 1, 85354 Freising, Germany.
  • Nellaker C; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7FZ, United Kingdom; Nuffield Department of Women's and Reproductive Health, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, United Kingdom.
  • Lindgren CM; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7FZ, United Kingdom.
  • Kulozik U; Food- and Bioprocess Engineering, TUM School of Life Sciences, Technical University of Munich, Weihenstephaner Berg 1, 85354 Freising, Germany.
  • Ecker J; ZIEL - Institute for Food and Health, Research Group Lipid Metabolism, Technical University of Munich, Freising, Germany.
  • Karampinos DC; Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Munich, Germany; Munich Institute of Biomedical Engineering, Technical University of Munich, Munich, Germany.
  • Claussnitzer M; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Genomic Medicine and Endocrine Division, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Harvard University, Boston, MA, USA.
  • Hauner H; Else Kröner-Fresenius-Center for Nutritional Medicine, Chair of Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Gregor-Mendel-Straße 2, 85354 Freising-Weihenstephan, Germany; Institute for Nutritional Medicine, School of Medicine, Technical University of Munich, Ge
EBioMedicine ; 79: 104020, 2022 May.
Article in En | MEDLINE | ID: mdl-35490555
ABSTRACT

BACKGROUND:

The adipocyte-hypertrophy associated remodeling of fat cell function is considered causal for the development of metabolic disorders. A better understanding of transcriptome and fatty acid (FA) related alterations with adipocyte hypertrophy combined with less-invasive strategies for the detection of the latter can help to increase the prognostic and diagnostic value of adipocyte size and FA composition as markers for metabolic disease.

METHODS:

To clarify adipocyte-hypertrophy associated transcriptomic alterations, fat cell size was related to RNA-Seq data from white adipose tissue and size-separated adipocytes. The relationship between adipocyte size and adipose tissue FA composition as measured by GC-MS was investigated. MR spectroscopy (MRS) methods for clinical scanning were developed to characterize adipocyte size and FA composition in a fast and non-invasive manner.

FINDINGS:

With enlarged adipocyte size, substantial transcriptomic alterations of genes involved in mitochondrial function and FA metabolism were observed. Investigations of these two mechanisms revealed a reciprocal relationship between adipocyte size and estimated thermogenic adipocyte content as well as depot-specific correlations of adipocyte size and FA composition. MRS on a clinical scanner was suitable for the in-parallel assessment of adipose morphology and FA composition.

INTERPRETATION:

The current study provides a comprehensive overview of the adipocyte-hypertrophy associated transcriptomic and FA landscape in both subcutaneous and visceral adipose tissue. MRS represents a promising technique to translate the observed mechanistic, structural and functional changes in WAT with adipocyte hypertrophy into a clinical context for an improved phenotyping of WAT in the context of metabolic diseases.

FUNDING:

Competence network for obesity (FKZ 42201GI1128), ERC (No 677661, ProFatMRI; No 875488, FatVirtualBiopsy), Else Kröner-Fresenius-Foundation.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Fatty Acids / Transcriptome Type of study: Prognostic_studies Limits: Humans Language: En Journal: EBioMedicine Year: 2022 Document type: Article
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Fatty Acids / Transcriptome Type of study: Prognostic_studies Limits: Humans Language: En Journal: EBioMedicine Year: 2022 Document type: Article