Transcriptome and fatty-acid signatures of adipocyte hypertrophy and its non-invasive MR-based characterization in human adipose tissue

Julius Honecker; Stefan Ruschke; Claudine Seeliger; Samantha Laber; Sophie Strobel; Priska Pröll; Christoffer Nellaker; Cecilia M Lindgren; Ulrich Kulozik; Josef Ecker; Dimitrios C Karampinos; Melina Claussnitzer; Hans Hauner

doi:10.1016/j.ebiom.2022.104020

Transcriptome and fatty-acid signatures of adipocyte hypertrophy and its non-invasive MR-based characterization in human adipose tissue

EBioMedicine. 2022 May:79:104020. doi: 10.1016/j.ebiom.2022.104020. Epub 2022 Apr 29.

Authors

Affiliations

¹ 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.
² Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Munich, Germany.
³ 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.
⁴ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁵ Food- and Bioprocess Engineering, TUM School of Life Sciences, Technical University of Munich, Weihenstephaner Berg 1, 85354 Freising, Germany.
⁶ 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.
⁷ 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.
⁸ ZIEL - Institute for Food and Health, Research Group Lipid Metabolism, Technical University of Munich, Freising, Germany.
⁹ 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.
¹⁰ 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.
¹¹ 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, Georg-Brauchle-Ring 62, Munich 80992, Germany. Electronic address: hans.hauner@tum.de.

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.

Keywords: Browning; Fatty acids; Magnetic resonance; Obesity; Transcriptomics; White adipose tissue.

Publication types

Review

MeSH terms

Adipocytes / metabolism
Adipose Tissue / metabolism
Fatty Acids* / metabolism
Humans
Hypertrophy / metabolism
Hypertrophy / pathology
Transcriptome*

Substances

Fatty Acids