Abstract

Obesity is the leading risk factor for type 2 diabetes (T2D). As such, understanding how individuals with obesity, who have T2D vs those who do not have T2D differ, will provide novel insights into T2D prevention and treatment methods. The occurrence of T2D differs in males and females across the lifespan, therefore adipose tissue characteristics are suspected to vary between the sexes. Additionally, because a high waist to hip ratio is associated with T2D regardless of sex or age, it is conceivable that characteristics of upper body (abdominal subcutaneous adipose tissue [abSAT] and visceral adipose tissue [VAT]), and lower body (femoral SAT [fmSAT]) adipose tissue differs. Perturbed adipose tissue preadipocyte, adipocyte, and immune cell profiles are a characteristic in obesity that has been implicated in the development of T2D. Therefore, the objective of this thesis is to determine how sex and regional adipose tissue characteristics differ in individuals with T2D. In answering this objective, a review of the literature, a novel flow cytometry protocol, and 3 experiments were conducted that resulted in one literature review, one methodology manuscript, and three original research manuscripts being produced. Major findings include novel results showing that in females, not males, fmSAT had a greater T cells presence than abSAT. It was also shown that fmSAT T cells are greater in females with obesity and T2D (OB+T2D) than females with obesity (OB). No regional differences in macrophages, NK cells, iNKT cells or B cells were observed. Lastly, we are the first to show that abSAT and fmSAT impaired glucose uptake independent of effects on myogenesis. These results provide a launching ground for future study of fmSAT T cells and the cross talk between adipose tissue and skeletal muscle in T2D pathology. Our studies demonstrate how sex and regional adipose tissue contribute to T2D, knowledge that will ultimately allow for the development of more individualized T2D prevention and treatment methods.