Decreased Expression of Amyloid Precursor Protein in Human Adipose Tissue with Weight Loss.

Recent prospective studies have demonstrated that mid-life obesity increases risk for Alzheimer's Disease. Amyloid-β, a neurotoxic fragment found in the plaques that characterize the brains of affected individuals, is derived by amyloid precursor protein (APP) cleavage and is associated with pro-inflammatory responses in neural and glial cells. In our recent studies, we demonstrated that APP was highly expressed in adipose tissue and upregulated in obese compared to non-obese individuals. To determine whether adipose tissue APP is altered by weight loss, we investigated gene expression levels in abdominal subcutaneous adipose tissue (SAT) from subjects with diet-induced weight loss or weight loss produced by gastric bypass surgery. Using quantitative real-time PCR, we compared APP gene expression in SAT of 10 obese individuals (Age 51±8) with a 7% weight loss (Pre BMI 35±6; Post BMI 33±7) produced by a 6 month diet intervention and 7 morbidly obese patients (Age 44±9) before and 1 year after gastric bypass surgery (Pre BMI 52±9; Post BMI 36±6). Adipose tissue APP expression was not changed with short term diet-induced weight loss (Pre 72±23 vs Post 78±18, relative level±STDEV, p=0.2). Weight loss produced by bypass surgery in morbidly obese subjects significantly decreased APP expression in SAT (97±26 vs 69±5, p=0.01). APP gene expression in SAT correlated with age in those with a BMI<35 (r=0.78, p=0.002) but not in those with a BMI > 35, suggesting SAT APP expression is dysregulated in morbidly obese individuals. In summary, APP is highly expressed in SAT in morbidly obese individuals and significantly decreased with weight loss. Whether decreases in APP expression with weight loss contribute to improvements in adipose tissue inflammation and metabolism remains to be further determined. [ABSTRACT FROM AUTHOR]