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The Adipocyte acquires a Fibroblast-like Transcriptional Signature in response to a High Fat Diet.

ABSTRACT: RNA-seq analysis of isolated adipocytes after 8, 20 and 34 weeks high fat diet. Our data demonstrate that the adipocyte responds to the HFD by adopting a fibroblast-like phenotype, characterized by enhanced expression of ECM, focal adhesion and cytoskeletal genes and suppression of many adipocyte programs most notably those associated with mitochondria. Purpose: Visceral white adipose tissue (vWAT) expands and undergoes extensive remodeling during diet-induced obesity. Much is known about the contribution of various stromal vascular cells to the remodeling process, but less is known of the changes that occur within the adipocyte as it becomes progressively dysfunctional. Here, we performed a transcriptome analysis of isolated vWAT adipocytes to assess global pathway changes occurring in response to a chronic high fat diet (HFD). Methods: C57BL/6J mice were fed a high fat diet (HFD) or chow for 8, 20 and 34 weeks. At each time, metabolic parameters were measured and RNAseq performed on RNA isolated from adipocyte and stromal vascular cell fractions of the corresponding perigonadal white adipose tissue (eWAT). Results: Our data demonstrate that the adipocyte responds to the HFD by adopting a fibroblast-like phenotype, characterized by enhanced expression of ECM, focal adhesion and cytoskeletal genes and suppression of many adipocyte programs most notably those associated with mitochondria. Conclusions: This study reveals that during obesity the adipocyte progressively becomes metabolically dysfunctional due to its acquisition of fibrogenic functions. We propose that mechano-responsive transcription factors such as MRTFA and SRF contribute to both upregulation of morphological genes as well as suppression of mitochondrial programs.

ORGANISM(S): Mus musculus

PROVIDER: GSE142187 | GEO | 2019/12/18

REPOSITORIES: GEO

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