Visceral adiposity and pro-inflammation: contributions and consequences of immunity
Date
2017
Authors
Magnuson, Aaron Mark, author
Foster, Michelle T., advisor
Weir, Tiffany, advisor
Colgan, Sean, committee member
Dow, Steve, committee member
Journal Title
Journal ISSN
Volume Title
Abstract
Obesity among Americans has reached a strikingly prevalent rate with ~36% of adults falling into this category. As this rate continues to rise, so do the number of individuals with chronic diseases associated with excessive adipose tissue accumulation. Dysregulation of adipose tissue is a fundamental driver of obesity associated comorbidities. In particular, deposition of adipose tissue within the visceral cavity is especially deleterious, while subcutaneous adipose tissue has been identified as being metabolically protective. Consequently, visceral adiposity is demonstrated to be more highly associated with increased pro-inflammation. This inflammation has been demonstrated to be the causal link between obesity and its associated comorbidities. The purpose of this research was to investigate why visceral adiposity is so detrimental. We propose that the lymphatic system is central to the heightened inflammatory potential associated with adipose tissue deposition in the visceral cavity. The visceral lymph node serves as the immune nexus between the visceral adipose tissue and the small intestines and is thus impacted by alterations in these tissues as a consequence of poor diet and obesity. In these studies we utilized mouse models of diet induced obesity (DIO) to elucidate the relationships between these tissues that potentially contribute to heightened pro-inflammatory potential of visceral adiposity relative to subcutaneous. We fed mice a high fat westernized diet (HFD) for 7 or 13 weeks, and then analyzed immune cell populations in the visceral and subcutaneous lymph iii nodes and adipose tissue and the small intestine, adipose tissue inflammatory markers, and lymph node morphology. Visceral adipose tissue had an inherently greater potential for pro-inflammation based on immune cell populations in lean controls relative to subcutaneous adipose tissue. Seven weeks of DIO was associated with decreased potential for immune suppression in the visceral adipose tissue, small intestines and visceral lymph nodes and elevated pro-inflammatory immune cell subsets. Consistent with this, pro-inflammatory cytokines were significantly elevated in the visceral adipose tissue. In association with this, visceral lymph nodes demonstrated hypertrophy, increases in total viable immune cells and immune cell subsets indicative of an adaptive like immune response. These changes were specific to the visceral cavity. Thirteen weeks of DIO caused a suppression of total viable immune cells and pro-inflammatory subsets in both the visceral adipose tissue and lymph nodes. Subcutaneous tissues were relatively unaffected. Alterations in immune cells were associated with significant fibrosis specific to the visceral lymph nodes. Increased incidence of comorbidities and immune related pathologies associated with visceral adiposity is likely, at least in part, a consequence of heightened pro-inflammation in the visceral lymph node as a result of chronic immune stimulation from both the visceral adipose tissue and small intestines. We propose that lymph node fibrosis is a result of chronic inflammation associated with obesity. In turn, this contributes to immune suppression that is associated increased susceptibility to pathogen infection and disease morbidity.