1. ¹Department of Internal Medicine, Catholic University, Rome, Italy
2. ²Unit for Neuromuscular Biology and Pathophysiology, Department of Biomedical Sciences, CNR Institute of Neurosciences, University of Padua, Padua, Italy
3. ³Centre of Experimental Researches, Catholic University, Rome, Italy
4. ⁴Department of General Surgery, Catholic University, Rome, Italy

Correspondence: Professor G Mingrone, Department of Internal Medicine, Catholic University, Largo A Gemelli, Rome 00168, Italy. E-mail: gmingrone@rm.unicatt.it

Received 5 September 2007; Revised 31 December 2007; Accepted 15 January 2008; Published online 19 February 2008.

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, 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 425.667.6 ng ml^{- 1} at 30 days vs 150.233.4 ng ml^{- 1} in controls (P<0.001) and dropped to 53.825.8 ng ml^{- 1} at 90 days (P<0.0001). TUNEL-positive nuclei were 66.0826.19 at 30 days 57 (34.5817 in controls, P<0.05) and 216.99129.42 nuclei per mm³ at 90 days (38.7518.36 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.