Anti-Inflammatory Effects of Cardiovascular Exercise: Role of Visceral Adipose Tissue

133 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2009.Chronic consumption of a diet high in saturated fat (HFD) combined with a sedentary lifestyle has led to the obesity epidemic and its associated metabolic complications. At the heart of the metabolic aberrations that lead to obesity-associated diseases is inflammation that occurs in the visceral white adipose tissue (WAT). Reducing WAT inflammation, even in the absence of body weight changes, improves the metabolic consequences of obesity, highlighting the importance of the physiology of the WAT in the treatment of metabolic diseases. Exercise (EX) has been shown to reduce systemic inflammation, and this effect may be mediated by an EX-associated reduction in WAT inflammation. The overarching hypothesis of this work was that EX lowers inflammation in the visceral WAT as well as in the periphery, and that the mechanism involves, but is not fully explained by, a reduction in visceral WAT. This hypothesis was tested using one human intervention trial and two animal studies. In the first study, previously sedentary older adults participated in 10 months of cardiovascular (Cardio) or non-cardiovascular (Flex) EX. Cardio experienced significant improvements in fitness, systemic inflammation (as measured by serum C-reactive protein, CRP), as well as total and central (i.e., trunk) fat. Only the decrease in trunk fat was significantly related to the reduction in CRP, suggesting that the mechanism behind the anti-inflammatory effect of EX may involve a reduction in visceral WAT. In the second study, Balb/c mice were fed an HFD for 12 wks and then were randomized to 1 of 4 groups where they either remained on HFD and sedentary (HFSED), were exercise trained (HFEX), switched to an LFD (LFSED), or switched to an LFD and exercise trained (HFEX) for 12 wks. LFD and EX had differential effects on WAT gene transcription (MCP-1, F4/80, IL1ra), IR, and HS. In the final animal study, C57BL/6 mice were fed an HFD for 6 wks and then were randomized to HFSED, HFEX, LFSED, or LFEX for a 6 or a 12-wk intervention. EX and LFD both decreased weight gain and relative body fat, although LFD had a more robust effect than EX. Reductions in visceral WAT explained the decreases in WAT inflammation, IR, and HS seen at 6 wks. However, by 12 wks, unique independent effects of EX and LFD emerged such that both treatments reduced WAT inflammation and metabolic complications. WAT macrophage infiltration was the most important independent predictor of IR whereas visceral fat mass most strongly predicted HS. In summary, there are unique metabolic consequences of a sedentary lifestyle and chronic consumption of an HFD. Both LFD and EX are critically important behavioral strategies to improve WAT health and whole body metabolic function.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD