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

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish
Article number104020
JournaleBioMedicine
Volume79
DOIs
StatePublished - May 2022

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • Browning
  • Fatty acids
  • Magnetic resonance
  • Obesity
  • Transcriptomics
  • White adipose tissue

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