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Short-term, but not extended, access to palatable diet diminishes amylin responsiveness in rat
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Abstracts / Appetite 54 (2010) 631–683
Diet-induced obesity, hyperamylinemia and amylin sensitivity C.N. BOYLE ∗ , M.M. ROSSIER, T.A. LUTZ Institute of Veterinary Physiology, University of Zürich, Zürich, Switzerland Amylin is co-secreted with insulin from the pancreas to control nutrient flux after a meal. Though amylin is a promising treatment of obesity and diabetes, it has been reported that obese animals are less responsive to amylin administration, suggesting that adiposity might render amylin less therapeutically effective. The first aim of our study was to assess the acute anorectic response to amylin in rats that were chronically fed a high fat diet (HF). We also tested if hyperamylinemia modifies amylin sensitivity independently of obesity. Male rats were maintained on standard chow or HF (60% kcal from fat) for 14 wk. At 9 wk, rats maintained on HF had elevated fasting levels of amylin and leptin, and at the time of sacrifice at 14 wk showed significant increases in visceral and subcutaneous adipose tissue. During the study, sensitivity to the anorectic effect of amylin was determined by injecting vehicle or amylin (5, 20, or 50 g/kg, s.c.) to non-fasted rats and monitoring food intake for 2 h. In the first 6 weeks, HF did not initially alter amylin-sensitivity; however, by wk 11, low doses of amylin only significantly suppressed food intake in the chow-fed rats. This suggests that amylin’s ability to inhibit food intake is reduced following long-term access to HF and the development of obesity. Our results demonstrate that amylin’s potency as an anorectic agent can be modified by chronic HF consumption. Though we cannot presently speak to underlying mechanisms, we have recently found that chronic hyperamylinemia alone, which is typically associated with obesity, does not cause amylin insensitivity in rats. doi:10.1016/j.appet.2010.04.029
Effect of sympathectomy and sympathectomy/vagotomy on reduction of food intake by cholecystokinin-8 and 33 T.A. BROWN ∗ , M.C. WASHINGTON, A.I. SAYEGH Gastroenterology Laboratory, Department of Biomedical Sciences, College of Veterinary Medicine, Tuskegee University, Tuskegee, AL, USA Reduction of food intake by CCK is vagally mediated. However, the role of the sympathetic innervation of the gut in this reduction has not been tested. We used three groups of rats, sympathectomy (SYMPX, celiaco-mesenteric ganglionectomy), sympathectomy/vagotomy (SYMPX/VGX) and sham rats injected with CCK-8, 33 (1, 3, and 5 nmol/kg) or saline i.p. followed by measuring the intake of 10% sucrose for a total of 120 min. In the SYMPX group, CCK-8 and -33 reduced meal size and increased the satiety ratio. In the same group, CCK-8 reduced the intermeal interval (IMI) but CCK-33 increased it. Devazepide, a CCK1 receptor antagonist failed to block this reduction. In the SYMPX/VGX group, both peptides reduced meal size, and CCK-33 reduced it more than CCK-8. Both peptides increased the IMI and satiety ratio. Devazepide blocked this effect while L365, 260 did not. In conclusion, removal of the sympathetic or combined sympathetic and parasympathetic innervations of the gut did not affect reduction of food intake by CCK-8 and 33. Therefore, another pathway(s) may mediate the reduction of food intake by CCK. doi:10.1016/j.appet.2010.04.031
Short-term, but not extended, access to palatable diet diminishes amylin responsiveness in rat C.N. BOYLE ∗ , M. MUNZ, P.Y. WIELINGA, D. STöCKER, T.A. LUTZ Institute of Veterinary Physiology, University of Zürich, Zürich, Switzerland
Racial differences in ghrelin response to glycemic load K.A. BROWNLEY 1,∗ , J.A. GALANKO 2 , S. HEYMEN 2 , A.L. 2 3 1 HINDERLITER , B. MACINTOSH UNC Dept Psychiatry, Chapel Hill, NC, USA 2 Dept Medicine, Chapel Hill, NC, USA 3 UNC Clincal and Translational Research Center, Chapel Hill, NC, USA
The pancreatic hormone amylin, which acts via the area postrema (AP) to reduce food intake, is reportedly less effective in obese humans and some rodent models of obesity. However, it is unknown what aspects of obesity alter amylin sensitivity. Here we test the hypothesis that short-term intake of a high-energy, palatable diet (Ensure chocolate), independent of obesity, is sufficient to cause amylin insensitivity in rodents. Male rats were offered Ensure liquid diet for either 3 days or 3 weeks, following which the responsiveness to both central (5 pmol, i3V) or peripheral (5 g/kg, ip) amylin were examined. Three weeks access to Ensure resulted in hyperphagia and weight gain, but sensitivity to the anorectic effects of amylin remain intact. Interestingly, when Ensure was only offered for 3 days, neither central nor peripheral administration of amylin attenuated food intake. However, amylin responsiveness was restored by placing the rats back on chow for 3 days, or increasing the dose of amylin (10 or 100 pmol, i3V). Finally, we examined if 3 days of Ensure-feeding modifies peripheral amylininduced cFos activation, and found Ensure does not alter expression in the AP, amylin’s central target site. These results suggest that the amylin insensitivity following short-term intake of palatable diet is reversible, dose-dependent, and may involve altered neuronal activation in central brain sites downstream of the AP. doi:10.1016/j.appet.2010.04.030
This study evaluated glycemic load (GL) effects on ghrelin and whether any observed effects of GL on ghrelin differed as a function of race. Twenty Black and 20 age- and body mass index-matched White women (10 each group normal weight vs. obese) completed in randomized order two 4-day weight-maintenance, mixed macronutrient high (212.5 ± 31.2) vs. low GL (107.5 ± 25.2) diets, each followed by an overnight fast and a test meal of similar composition (high GL = 59.1 ± 5.9; low GL = 31.3 ± 3.6). Blood samples were obtained before and for 3 h after each test meal and later assayed for total ghrelin (TG), insulin, and glucose. Postprandial TG area under the curve (AUC) was significantly less after the high vs. low GL meal (p < 0.0008), with this effect tending to differ by race (White women, p < 0.004 vs. Black women, p > 0.14). GlucoseAUC (p < 0.03) and insulinAUC (p < 0.02) were significantly greater after the high vs. low GL meal, with these effects being more pronounced in White (ps < 0.005) compared to Black (ps > 0.70) women. These findings are consistent with: (1) observations linking high GL to greater insulin response, (2) an inverse relationship between postprandial insulin and ghrelin levels, and (3) ghrelin downregulation with prolonged high GL dietary intake. Future studies should consider race as a potentially important modifier of GL effects on appetite hormones. doi:10.1016/j.appet.2010.04.032
Abstracts / Appetite 54 (2010) 631–683
Diet-induced obesity, hyperamylinemia and amylin sensitivity C.N. BOYLE ∗ , M.M. ROSSIER, T.A. LUTZ Institute of Veterinary Physiology, University of Zürich, Zürich, Switzerland Amylin is co-secreted with insulin from the pancreas to control nutrient flux after a meal. Though amylin is a promising treatment of obesity and diabetes, it has been reported that obese animals are less responsive to amylin administration, suggesting that adiposity might render amylin less therapeutically effective. The first aim of our study was to assess the acute anorectic response to amylin in rats that were chronically fed a high fat diet (HF). We also tested if hyperamylinemia modifies amylin sensitivity independently of obesity. Male rats were maintained on standard chow or HF (60% kcal from fat) for 14 wk. At 9 wk, rats maintained on HF had elevated fasting levels of amylin and leptin, and at the time of sacrifice at 14 wk showed significant increases in visceral and subcutaneous adipose tissue. During the study, sensitivity to the anorectic effect of amylin was determined by injecting vehicle or amylin (5, 20, or 50 g/kg, s.c.) to non-fasted rats and monitoring food intake for 2 h. In the first 6 weeks, HF did not initially alter amylin-sensitivity; however, by wk 11, low doses of amylin only significantly suppressed food intake in the chow-fed rats. This suggests that amylin’s ability to inhibit food intake is reduced following long-term access to HF and the development of obesity. Our results demonstrate that amylin’s potency as an anorectic agent can be modified by chronic HF consumption. Though we cannot presently speak to underlying mechanisms, we have recently found that chronic hyperamylinemia alone, which is typically associated with obesity, does not cause amylin insensitivity in rats. doi:10.1016/j.appet.2010.04.029
Effect of sympathectomy and sympathectomy/vagotomy on reduction of food intake by cholecystokinin-8 and 33 T.A. BROWN ∗ , M.C. WASHINGTON, A.I. SAYEGH Gastroenterology Laboratory, Department of Biomedical Sciences, College of Veterinary Medicine, Tuskegee University, Tuskegee, AL, USA Reduction of food intake by CCK is vagally mediated. However, the role of the sympathetic innervation of the gut in this reduction has not been tested. We used three groups of rats, sympathectomy (SYMPX, celiaco-mesenteric ganglionectomy), sympathectomy/vagotomy (SYMPX/VGX) and sham rats injected with CCK-8, 33 (1, 3, and 5 nmol/kg) or saline i.p. followed by measuring the intake of 10% sucrose for a total of 120 min. In the SYMPX group, CCK-8 and -33 reduced meal size and increased the satiety ratio. In the same group, CCK-8 reduced the intermeal interval (IMI) but CCK-33 increased it. Devazepide, a CCK1 receptor antagonist failed to block this reduction. In the SYMPX/VGX group, both peptides reduced meal size, and CCK-33 reduced it more than CCK-8. Both peptides increased the IMI and satiety ratio. Devazepide blocked this effect while L365, 260 did not. In conclusion, removal of the sympathetic or combined sympathetic and parasympathetic innervations of the gut did not affect reduction of food intake by CCK-8 and 33. Therefore, another pathway(s) may mediate the reduction of food intake by CCK. doi:10.1016/j.appet.2010.04.031
Short-term, but not extended, access to palatable diet diminishes amylin responsiveness in rat C.N. BOYLE ∗ , M. MUNZ, P.Y. WIELINGA, D. STöCKER, T.A. LUTZ Institute of Veterinary Physiology, University of Zürich, Zürich, Switzerland
Racial differences in ghrelin response to glycemic load K.A. BROWNLEY 1,∗ , J.A. GALANKO 2 , S. HEYMEN 2 , A.L. 2 3 1 HINDERLITER , B. MACINTOSH UNC Dept Psychiatry, Chapel Hill, NC, USA 2 Dept Medicine, Chapel Hill, NC, USA 3 UNC Clincal and Translational Research Center, Chapel Hill, NC, USA
The pancreatic hormone amylin, which acts via the area postrema (AP) to reduce food intake, is reportedly less effective in obese humans and some rodent models of obesity. However, it is unknown what aspects of obesity alter amylin sensitivity. Here we test the hypothesis that short-term intake of a high-energy, palatable diet (Ensure chocolate), independent of obesity, is sufficient to cause amylin insensitivity in rodents. Male rats were offered Ensure liquid diet for either 3 days or 3 weeks, following which the responsiveness to both central (5 pmol, i3V) or peripheral (5 g/kg, ip) amylin were examined. Three weeks access to Ensure resulted in hyperphagia and weight gain, but sensitivity to the anorectic effects of amylin remain intact. Interestingly, when Ensure was only offered for 3 days, neither central nor peripheral administration of amylin attenuated food intake. However, amylin responsiveness was restored by placing the rats back on chow for 3 days, or increasing the dose of amylin (10 or 100 pmol, i3V). Finally, we examined if 3 days of Ensure-feeding modifies peripheral amylininduced cFos activation, and found Ensure does not alter expression in the AP, amylin’s central target site. These results suggest that the amylin insensitivity following short-term intake of palatable diet is reversible, dose-dependent, and may involve altered neuronal activation in central brain sites downstream of the AP. doi:10.1016/j.appet.2010.04.030
This study evaluated glycemic load (GL) effects on ghrelin and whether any observed effects of GL on ghrelin differed as a function of race. Twenty Black and 20 age- and body mass index-matched White women (10 each group normal weight vs. obese) completed in randomized order two 4-day weight-maintenance, mixed macronutrient high (212.5 ± 31.2) vs. low GL (107.5 ± 25.2) diets, each followed by an overnight fast and a test meal of similar composition (high GL = 59.1 ± 5.9; low GL = 31.3 ± 3.6). Blood samples were obtained before and for 3 h after each test meal and later assayed for total ghrelin (TG), insulin, and glucose. Postprandial TG area under the curve (AUC) was significantly less after the high vs. low GL meal (p < 0.0008), with this effect tending to differ by race (White women, p < 0.004 vs. Black women, p > 0.14). GlucoseAUC (p < 0.03) and insulinAUC (p < 0.02) were significantly greater after the high vs. low GL meal, with these effects being more pronounced in White (ps < 0.005) compared to Black (ps > 0.70) women. These findings are consistent with: (1) observations linking high GL to greater insulin response, (2) an inverse relationship between postprandial insulin and ghrelin levels, and (3) ghrelin downregulation with prolonged high GL dietary intake. Future studies should consider race as a potentially important modifier of GL effects on appetite hormones. doi:10.1016/j.appet.2010.04.032