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
Affiliations
Julius Honecker
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; Corresponding authors at: 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.
Stefan Ruschke
Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Munich, Germany
Claudine Seeliger
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
Samantha Laber
Broad Institute of MIT and Harvard, Cambridge, MA, USA
Sophie Strobel
Broad Institute of MIT and Harvard, Cambridge, MA, USA
Priska Pröll
Food- and Bioprocess Engineering, TUM School of Life Sciences, Technical University of Munich, Weihenstephaner Berg 1, 85354 Freising, Germany
Christoffer Nellaker
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
Cecilia M. Lindgren
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
Ulrich Kulozik
Food- and Bioprocess Engineering, TUM School of Life Sciences, Technical University of Munich, Weihenstephaner Berg 1, 85354 Freising, Germany
Josef Ecker
ZIEL - Institute for Food and Health, Research Group Lipid Metabolism, Technical University of Munich, Freising, Germany
Dimitrios C. Karampinos
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
Melina Claussnitzer
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
Hans Hauner
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; Corresponding authors at: 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.
Summary: 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.
