| Summary: | Obesity is characterized by the accumulation of excess adipose tissue and has become a global health burden as the rates of obesity in both adults and children continue an upward trend year after year. Obesity is an important public health concern as it has been linked to increased prevalence of comorbidities such as type 2 diabetes, fatty liver, cardiovascular complications and cancer. Adipocytes are exquisitely sensitive to energy demands, quickly responding by releasing fatty acids, storing excess calories as triglycerides and/or secreting adipokines. The ability of the adipocyte to carry out its important functions requires perpetual remodeling of the extracellular matrix (ECM) surrounding the adipocyte. Metabolic dysfunction and fibrosis arise when the healthy balance of remodeling becomes dysregulated. The long-term goal of this project was to gain a deeper understanding of the events occurring within an adipocyte in the context of weight gain. I hypothesized that the adipocyte would play an active role in remodeling of the ECM. To test this hypothesis, I fed C57/Bl6 mice either high fat diet (HFD) or chow diet for 8, 20 and 34 weeks, at which time, the perigonadal adipose tissue was digested to isolate the adipocyte fraction and RNA-seq analysis was performed. My data demonstrate that adipocytes responded to their obesogenic, pro-inflammatory environment through upregulation of ECM-related genes after only 8 weeks of HFD coupled with declining expression of mitochondrial genes and increasing genes associated with endoplasmic reticulum (ER) stress after 20 and 34 weeks of HFD. Overall, these data give a novel view into the dysfunctional state of isolated adipocytes over a time course of HFD and response to the changing microenvironment.
MICAL2 is an atypical actin-modulating protein that has been shown to be involved in the regulation of MRTFA/SRF signaling and in cancer progression. I demonstrated for the first time that MICAL2 expression is enriched in the stromal vascular fraction of adipose tissue and is upregulated with HFD and pro-fibrotic stimulus, TGF-β1. I also demonstrated that MICAL2 is an anti-adipogenic and pro-fibrogenic protein. Altogether, the novel biology uncovered suggests a role for MICAL2 in adipose tissue remodeling which warrants further investigation. === 2021-06-14T00:00:00Z
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