The impact of diet-induced obesity and exercise on adipose-resident stem cells

Recent studies suggest that vascular-associated multipotent stem/stromal cells exist in adipose tissue that can influence extracellular matrix (ECM) remodeling during lipid filling and adipose expansion. Both mesenchymal stem cells (referred to as adipose-derived stromal cells, or ADSCs) and pericytes may secrete factors such as collagen and metalloproteinases that can allow for tissue turnover. Therefore, the primary goal of this dissertation was to examine the impact of long-term high fat feeding on vascular-associated stem/stromal cell quantity and function, as well as the capacity for endurance exercise to mitigate these responses. Two studies were conducted. In the first, male C57BL/6J mice were placed on control or high fat diet (HFD) for 8 wk prior to and following initiation of a 16 wk treadmill exercise program. ADSCs (Sca-1+CD45-) were isolated from epididymal adipose tissue and mRNA was evaluated using high throughput qPCR. While resulting in a total increase in ADSC quantity, HFD decreased the relative quantity of ADSCs and markedly altered gene expression related to ECM remodeling (Col1α1, MMP2, MMP9, Timp1). Exercise did not reverse these changes. In the second study, a multiplex flow cytometry strategy was developed to evaluate the pericyte fraction using the prototypical proteoglycan cell surface marker, neural/glial antigen 2 (NG2), including two pericyte subtypes based on Nestin expression (+/-). Male and female NG2-DsRed x Nestin-GFP reporter mice were placed on control or HFD for 6 wk prior to and following initiation of a 12 wk treadmill exercise program. NG2+Nestin- (Type 1 pericyte) and NG2+Nestin+ (Type 2 pericyte) cells were isolated from inguinal adipose tissue of these double transgenic animals, and quantity was evaluated after gating for endothelial (CD31+) and hematopoietic cells (CD45+) (Lin fraction) using flow cytometry. Delineation of subtype quantitation was not pursued due to the fact that Type 2 pericyte quantity was very low in adipose tissue. Total NG2+Lin- pericyte quantity was increased in males, but not in females, in response to HFD. Interestingly, exercise suppressed the rise in pericyte quantity in males. HFD did not significantly alter cell surface marker expression, and adipogenic progenitor cell marker expression remained low. In conclusion, the results of these studies suggest that ADSC relative quantity is decreased and adipose-resident NG2+ pericyte relative quantity is increased in response to long-term HFD. Based on gene expression and cell surface marker expression data, engagement in adipogenesis does not likely account for the alteration in adipose-resident stem cell quantity due to the obese condition. Striking changes in ECM gene expression suggest that ADSCs strongly contribute to ECM remodeling during tissue expansion. Finally, the fact that ECM gene expression was not mitigated by exercise training may imply that full recovery of adipose tissue health is dependent on a restriction in energy intake.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Kinesiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2016

Author dc:creator

• Pincu, Yair

Contributors dc:contributor

• Boppart, Marni D.
• Woods, Jeffrey
• Wilund, Kenneth
• Koh, Timothy

• Pericytes
• Adipose-derived stromal cells (ADSCs)
• Fibrosis

Statement dc:rights

• Copyright 2016 Yair Pincu

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/90898

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/90898