Skip to Main Content
 

Global Search Box

 
 
 

ETD Abstract Container

Abstract Header

Determining the Physiological Contribution of Adipocyte Subpopulations

Abstract Details

2019, Doctor of Philosophy (PhD), Ohio University, Biological Sciences (Arts and Sciences).
With the rise of obesity and the associated complications, adipose tissue, which was once thought to be an inert organ, has emerged as one of the important endocrine organs in disease pathology. Although adipose tissues appear to be homogeneous, recent studies have demonstrated the diverse developmental origins and functions of adipocytes within each region (depot) of fat. Our lab has discovered at least three distinct adipocyte subpopulations marked by the expression of Wilms’ Tumor 1 (Wt1), Transgelin (Tagln), and Myxovirus 1 (Mx1), termed Type 1, 2, and 3, respectively. These adipocyte subpopulations exhibit differential response to insulin, growth hormone (GH), and inflammatory cytokines. While the majority of the research in this dissertation focuses on Type 1 subpopulation, our recent work implicates both Type 1 and Type 2 adipocytes in diabetes-related pathologies. Firstly, Type 1 subpopulation is derived from mesothelial cells. Mesothelial cells constitute a monolayer encompassing the visceral organs and visceral adipose tissue that are capable of secreting pro-inflammatory cytokines (e.g. IL6, IL-8) in response to inflammatory signals. Interestingly, Type 1 adipocytes are only found in visceral depots (where chronic inflammation occurs during obesity), and Type 1 preadipocytes are capable of maintaining high MCP-1 level basally. In vitro migration assay shows that Type 1 preadipocytes recruit macrophages when co-cultured, suggesting that Type 1 subpopulation has inflammatory characteristics. Furthermore, tissue clearing showed that Type 1 are distributed closest to urogenital organs (kidneys and gonads) and distal to the digestive tract (ileum and colon). Given the proximity of these Type 1 cells to neighboring organs, they potentially influence the overall function of these organs, as seen in creeping fat of inflammatory bowel disease. Lastly, we explore the effect of GH on adipocytes as it differentially affects adipocyte subpopulations. GH-induced lipolysis in adipocytes is a regulated pathway by both mitogen-activated protein kinase kinase (MEK)/ extracellular signaling-regulated kinase (ERK) and signal transducer and activator of transcription 5 (STAT5), with MEK/ERK pathway as the major suppressor of anti-lipolytic protein fat specific protein 27 (FSP27). Overexpression of FSP27 is sufficient to abrogate the lipolytic effect of GH. An increase in free fatty acid levels are known to disrupt insulin signaling, leading to insulin resistance. Because Type 2 is highly responsive to GH action, these cells could be responsible for the increase in fatty acid level, upon GH stimulation, and may contribute to GH-mediated insulin resistance. Thus, the involvement of adipose tissues in numerous disease state can possibly be attributed to the presence of adipocyte subpopulations that make up these depots. The studies described here contribute to the deeper understanding of adipose biology with respect to adipocyte subpopulations to unravel the pathogenesis of insulin resistance in excess GH and obese states.
Kevin Lee, PhD (Advisor)
Fabian Benencia, PhD (Committee Member)
Darlene Berryman, PhD (Committee Member)
Vishwajeet Puri, PhD (Committee Member)
Kristin Stanford, PhD (Committee Member)
170 p.

Recommended Citations

Citations

  • Luong, Q. V. (2019). Determining the Physiological Contribution of Adipocyte Subpopulations [Doctoral dissertation, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1565279745478695

    APA Style (7th edition)

  • Luong, Quyen. Determining the Physiological Contribution of Adipocyte Subpopulations . 2019. Ohio University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1565279745478695.

    MLA Style (8th edition)

  • Luong, Quyen. "Determining the Physiological Contribution of Adipocyte Subpopulations ." Doctoral dissertation, Ohio University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1565279745478695

    Chicago Manual of Style (17th edition)