Increased oral and decreased intestinal sensitivity to sucrose in obese, prediabetic CCK-A receptor-deficient OLETF rats

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Abstract
CCK-A receptor-deficient Otsuka Long-Evans Tokushima fatty (OLETF) rats are hyperphagic and develop obesity and Type 2 diabetes. In this strain, taste preference functions have not been investigated. Therefore, a series of short-access, two-bottle tests were performed in age-matched prediabetic OLETF and nonmutant Long-Evans Tokushima Otsuka (LETO) rats to investigate preference for sucrose (0.03, 0.1, 0.3, or 1.0 M) presented with a choice of water. To discern orosensory from postgastric factors that may contribute to this preference, in a separate experiment, rats were allowed to sham feed sucrose in the absence or presence of duodenal sucrose infusion (0.3, 0.6, or 1.0 M). In the two-bottle real-feeding tests, OLETF rats exhibited a greater preference for 0.3 M sucrose (91.2 ± 1.7 and 78.5 ± 3.4% for OLETF and LETO, respectively; P < 0.01) and 1.0 M sucrose (65.3 ± 1.2 and 57.5 ± 2.7% for OLETF and LETO, respectively; P < 0.05) than LETO rats. OLETF rats also sham fed less of the lowest (0.03 M; 33.8 ± 4.8 and 58.3 ± 7.3 ml for OLETF and LETO, respectively; P < 0.05) and more of the highest (1.0 M; 109.9 ± 6.5 and 81.0 ± 3.9 ml for OLETF and LETO, respectively; P < 0.01) concentration of sucrose relative to LETO rats. Finally, intraduodenal sucrose infusions (0.6 and 1.0 M) produced a smaller reduction of 0.3 M sham sucrose intake [14.1 ± 8.1 vs. 52.5 ± 3.3 ml and 49.4 ± 8.0 vs. 82.4 ± 3.2 ml for 0.6 M ( P < 0.01) and 1.0 M ( P < 0.05) infusions in OLETF and LETO, respectively]. These findings demonstrate that OLETF rats display an increased preference for sucrose, an effect that is at least partially influenced by the orosensory stimulating effect of sucrose. This enhanced responsiveness to oral stimulation, coupled with the deficit in responding to the postingestive feedback of intestinal sucrose, may contribute additively to the development of hyperphagia and weight gain in OLETF rats.