(1) BACKGROUND: There are currently very few interventions performed within a community setting that compare the effects of physical activity (PA) versus PA plus weight loss on cancer and chronic disease risk in older African Americans. Therefore, we investigated the impact of an 8 week (24 session) PA intervention compared to a PA plus weight loss intervention on fat mass, glucose metabolism, and markers of inflammation in older, overweight and obese African Americans. (2) METHODS: Subjects were randomized to a PA (n = 83) or PA plus weight loss (n = 72) intervention that met three times weekly for 8 weeks. At baseline and post-intervention, anthropometrics, body composition, systemic inflammation (high-sensitivity C-reactive protein, tumor necrosis factor-alpha, and interleukin 6), fasting glucose, insulin and homeostasis model assessment-insulin resistance (HOMA-IR) were determined. (3) RESULTS: Subjects had a mean age of 67 years (SD = 5.3) and were mostly women (88%). The PA plus weight loss group lost more total and visceral fat than the PA group (-4.0% versus +0.6% and -4.1% versus +3.7%, respectively, p < 0.01 for both). Changes in inflammation and glucose metabolism were similar between groups post-intervention. Within the PA plus weight loss group only, serum insulin and HOMA-IR decreased significantly. (4) CONCLUSIONS: PA combined with weight loss can decrease total and visceral fat mass and improve insulin sensitivity, confirming that these cancer- and chronic disease-related risk factors are influenced by relatively modest lifestyle changes in the short term.

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