High saturated-fat diet induces apoptosis in rat enterocytes and blunts GIP and insulin-secretive response to oral glucose load

Abstract

Lipoapoptosis has been described in many organs and tissues, but never in enterocytes. We hypothesized that a high saturated-fat diet can induce duodenal enterocyte apoptosis and impair gastric inhibitory polypeptide (GIP) secretion. Forty male Wistar rats, approximately 4 months old, were randomized on standard laboratory or purified tripalmitin-based high-fat diet (59% calories). An oral-glucose tolerance test was performed after 30 and 90 days of diet to measure plasma glucose, insulin and GIP. Duodena were processed for histology and immunohistochemistry by transferase-mediated dUTP nick end-labeling (TUNEL) method. Apoptosis was confirmed by enzyme-linked immunosorbent assay. Glycemic response was significantly higher (P < 0.01 vs controls) in rats after 90 days. Insulin curve was markedly increased at 30 days, while it was blunted at 90 days. GIP area under the curve was 425.6 +/- 67.6 ng ml(-1) at 30 days vs 150.2 +/- 33.4 ng ml(-1) in controls (P < 0.001) and dropped to 53.8 +/- 25.8 ng ml(-1) at 90 days (P < 0.0001). TUNEL-positive nuclei were 66.08+/-26.19 at 30 days 57 (34.58+/-17 in controls, P < 0.05) and 216.99 +/- 129.42 nuclei per mm(3) at 90 days (38.75 +/- 18.36 in controls, P < 0.0001). A high saturated-fat diet stimulates GIP secretion but with time induces apoptosis of duodenal villi epithelium, showing for the first time that enterocytes are also prone to lipoapoptosis. The reduction of circulating GIP levels might contribute to hypoinsulinemia and hyperglycemia.