Abstract
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). The 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. 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.
Highlights
Unhealthy remodeling of adipose tissue due to over feeding involves enhanced deposition and decreased degradation or turnover of extracellular matrix (ECM), combined with an increase in crosslinking and stiffening of ECM fibers leading to adipocyte dysfunction, reduced adipogenic capacity and fibrosis with all contributing to whole body metabolic dysfunction, including type 2 diabetes and cardiovascular complications[12,13]
To begin to evaluate adipose tissue remodeling in the context of weight gain and progression of obesity, we fed C57/Bl6J mice either chow diet (CD) or 60% high fat diet (HFD) over a time course of 8, 20 and 34 weeks starting from 6 weeks of age
Examination of perigonadal adipose tissue cross sections stained with Hematoxylin and Eosin (H&E) revealed that HFD led to larger adipocytes and enhanced staining intensity surrounding the adipocytes compared to CD at all times (Fig. 1C)
Summary
Unhealthy remodeling of adipose tissue due to over feeding involves enhanced deposition and decreased degradation or turnover of ECM, combined with an increase in crosslinking and stiffening of ECM fibers leading to adipocyte dysfunction, reduced adipogenic capacity and fibrosis with all contributing to whole body metabolic dysfunction, including type 2 diabetes and cardiovascular complications[12,13]. Whereas obesity is accompanied by an infiltration of B cells and various T cells (i.e. NK and Th1 cells) and polarization of M1 macrophages as well as a reduction in Tregs and ILCs leading to inflammation and associated insulin resistance. In contrast to our extensive understanding of the many changes occurring in the stromal cell compartment of adipose tissue with obesity, less is known about the adipocyte-specific processes leading to an unhealthy adipocyte. Our data demonstrate that adipocytes respond to a HFD by adopting a more fibroblast-like phenotype characterized by enhanced expression of ECM, cell adhesion and cytoskeletal genes along with suppression of adipocyte programs most importantly mitochondrial-related and lipolytic genes. We discuss the potential role of the morphological changes and associated transcriptional regulators in upregulating fibroblast-like genes and in suppressing normal adipocyte functions
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