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Gastric emptying of hexose sugars in healthy humans. Effects of osmolality and molecular structure
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Abstracts / Appetite 52 (2009) 815–868
Novel insight into ghrelin secretion in rats. New RAPID method for blood processing M. GOEBEL ∗ , A. STENGEL, L. WANG, Y. TACHE, J.R. REEVE UCLA, Los Angeles, CA, Los Angeles, CA, USA Ghrelin circulates in acylated (A-Ghr) and desacylated (D-Ghr) forms. A-Ghr stimulates food intake while D-Ghr may modulate AGhr’s action. Studies describe total ghrelin (T-Ghr) and A-Ghr and ratio of T/A ghrelin in the systemic circulation varying from 1:10 up to 1:50, probably due to not-optimized blood sampling as A-Ghr is rapidly degraded. Aim: To assess changes in T-Ghr and A-Ghr serum levels by RIA under different metabolic conditions in rats using a novel method maximizing A-Ghr recovery. Methods: Blood was withdrawn at 8AM from ad libitum fed and 24-h fasted conscious rats (n = 5/group) with jugular vein catheter. EDTA-blood was processed using the RAPID method (Refrigerated temperatures, Acidic pH, Protease inhibitors, Isotopic recovery standards, Dilution). Results: T-Ghr levels increased 2.8-fold after fasting compared to fed rats (p < 0.001). A-Ghr levels were also 3-fold higher after fasting (p < 0.001). The T/A ghrelin ratio remained 1:5 under both metabolic conditions. A standard blood sampling method (EDTA-blood) resulted in a significant increase in T-Ghr and A-Ghr after fasting, however the ratio was 1:41 and differed from ad libitum feeding (1:19). The standard method resulted in a > 80% A-Ghr loss compared to the RAPID method. Conclusions: Fasting increases T-Ghr and A-Ghr levels without influencing the ratio compared to fed rats assessed by the RAPID method that prevents A-Ghr degradation. The low T/A-Ghr ratio and high A-Ghr levels with RAPID compared to standard method points to key importance of proper blood processing before A-Ghr measurement to avoid false estimates. doi:10.1016/j.appet.2009.04.082
Gastric emptying of hexose sugars in healthy humans. Effects of osmolality and molecular structure A. GOPINATH 1,∗ , T. LITTLE 1 , A. MCGLONE 1 , E. PATEL 1 , D. LASSMAN 1 , S. RHODES 2 , J. MCLAUGHLIN 1 , D. THOMPSON 1 1 Manchester University, Manchester, United Kingdom 2 Salford Royal Hospital Trust, Manchester, United Kingdom It has been suggested that hexose sugars signal to the brain to slow gastric emptying (GE) via osmoreceptor stimulation in the small intestine; however, equi-osmolar glucose and fructose appear to empty differently, and large inter-individual differences in the responses to sugars are apparent. Therefore, we aimed to (i) examine the effects of hexose type as well as osmolality, on GE and (ii) determine whether GE responses were consistent within individuals. 23 healthy lean adults were studied to evaluate effects of 250, 500 and 1000 mOsmol solutions of glucose, galactose, fructose, and its poorly absorbed analogue, tagatose, using water, NaCl and lactulose as volumetric, and osmotic, controls. GE was assessed using a 13 C-acetate breath test. 3 subjects subsequently underwent 32 studies to evaluate intra-individual reproducibility. At 250 mOsmol, a sugar-specific effect was apparent: tagatose slowed GE (P < 0.05) compared with water, glucose and fructose. Fructose (P < 0.05), but not glucose and galactose, slowed GE but with substantial inter-individual differences in responsiveness. As the osmolality increased, GE of all hexoses was more potently slowed (P < 0.001), and the differences between them were abolished. 500 mOsmol solutions of lactulose and saline did not, whereas equi-osmolar solutions of glucose, fructose and tagatose did, slow GE when compared with water (P < 0.05). While inter-individual differences existed in the response to 250 mOsmol solutions of fructose, the response within an individual was consistent. While all hexose sugars slow GE at higher osmolarities, tagatose, and in some subjects, fructose, slowed GE more potently
than glucose or galactose at lower osmolality indicating that hexose-specific effects must operate on gut-to-brain signalling. doi:10.1016/j.appet.2009.04.083 Chronic sucrose intake reduces satiety-related activity in hypothalamic oxytocin neurons B.A. GOSNELL 1,∗ , P.K. OLSZEWSKI 2 , H.B. SCHIOTH 2 , M.K. GRACE 1 , A.S. LEVINE 1 1 University of Minnesota, St. Paul, MN, USA 2 Uppsala University, Uppsala, Sweden Oxytocin (OT) is one of many peptides thought to play a role in satiety. In light of the inhibitory effect of opioids on the activation of OT neurons, and the hypothesized role of opioids in mediating palatability, we measured whether long-term consumption of a sweet vs. a non-sweet diet would alter OT activity in a manner similar to that of opioids. Male rats were adapted to a food restriction regimen (2 h/day). Half the rats were given a sucrose-based diet for 20 days, while the other half was given a cornstarch-based diet (n = 14 per diet group). On the 21st day, half the rats in each group were given the opposite diet, and all diets were removed after 45 min. They were deeply anesthetized and perfused 60 min later. Double immunohistochemical staining (c-Fos and OT) was performed on coronal sections. The percentage of c-Fos positive OT cells in the PVN was significantly reduced in rats fed the sucrosebased diet, regardless of whether they received the sucrose or the cornstarch diet on day 21 (35.2 ± 3.5% for starch diet vs. 20.8 ± 2.7% for sucrose diet, p < 0.01). A similar pattern was observed in the supraoptic nucleus. This suggests that sucrose intake reduced activity in the OT system, and that the effect is not an acute effect of sucrose intake. The findings indicate that the consumption of sugar, in addition to providing taste reward, may also decrease activity in pathways that act as satiety systems. Decreased activity of satiety signals, therefore, could lead to overconsumption of foods other than sugar. Supported by NIH DA 021280. doi:10.1016/j.appet.2009.04.084 CD36 deletion is associated with decreased OEA production in the mouse small intestine A. GUIJARRO ∗ , J. FU, G. ASTARITA, D. PIOMELLI Department of Pharmacology, University of California, Irvine, Irvine, CA, USA Oleoylethanolamide (OEA) is a lipid-derived satiety factor produced by small intestinal enterocytes in response to fat ingestion. We previously showed that the fatty-acid transport protein CD36 plays a key role in mediating small-intestinal OEA biosynthesis following intra-duodenal fat infusion. Here we examined the impact of CD36 deletion on normal OEA production and feeding behavior in mice. Food intake (FI) was continuously analyzed in adult male CD36-null mice and wild-type C57BL/6J mice (WT) under free-feeding conditions for 12 consecutive days using an automated system. In a separate experiment, OEA levels were measured by LC/MS in a panel of tissues obtained from WT and CD36-null mice sacrificed during the dark or the light phase. OEA levels were lower in jejunum of CD36-null mice. No such difference was observed in other tissues, including duodenum, liver, fat and brain. No change was observed in the uptake of saturated or unsaturated fatty acids in duodenum and jejunum of null mice, compared to WT. Total FI was higher in CD36-null mice. This effect was observed mainly during the light phase and was associated with higher meal frequency and meal size and lower postmeal interval and satiety ratio. No genotype differences were found in plasma cholesterol, triacylglycerols, glucose, -hydroxybutyrate, leptin, adiponectin or insulin. These results support the hypothesis that CD36 contributes importantly to OEA production in the small intestine. The findings further suggest that CD36-null mice may have impaired satiety, which might be partly due to a decreased OEA signaling. doi:10.1016/j.appet.2009.04.085
Abstracts / Appetite 52 (2009) 815–868
Novel insight into ghrelin secretion in rats. New RAPID method for blood processing M. GOEBEL ∗ , A. STENGEL, L. WANG, Y. TACHE, J.R. REEVE UCLA, Los Angeles, CA, Los Angeles, CA, USA Ghrelin circulates in acylated (A-Ghr) and desacylated (D-Ghr) forms. A-Ghr stimulates food intake while D-Ghr may modulate AGhr’s action. Studies describe total ghrelin (T-Ghr) and A-Ghr and ratio of T/A ghrelin in the systemic circulation varying from 1:10 up to 1:50, probably due to not-optimized blood sampling as A-Ghr is rapidly degraded. Aim: To assess changes in T-Ghr and A-Ghr serum levels by RIA under different metabolic conditions in rats using a novel method maximizing A-Ghr recovery. Methods: Blood was withdrawn at 8AM from ad libitum fed and 24-h fasted conscious rats (n = 5/group) with jugular vein catheter. EDTA-blood was processed using the RAPID method (Refrigerated temperatures, Acidic pH, Protease inhibitors, Isotopic recovery standards, Dilution). Results: T-Ghr levels increased 2.8-fold after fasting compared to fed rats (p < 0.001). A-Ghr levels were also 3-fold higher after fasting (p < 0.001). The T/A ghrelin ratio remained 1:5 under both metabolic conditions. A standard blood sampling method (EDTA-blood) resulted in a significant increase in T-Ghr and A-Ghr after fasting, however the ratio was 1:41 and differed from ad libitum feeding (1:19). The standard method resulted in a > 80% A-Ghr loss compared to the RAPID method. Conclusions: Fasting increases T-Ghr and A-Ghr levels without influencing the ratio compared to fed rats assessed by the RAPID method that prevents A-Ghr degradation. The low T/A-Ghr ratio and high A-Ghr levels with RAPID compared to standard method points to key importance of proper blood processing before A-Ghr measurement to avoid false estimates. doi:10.1016/j.appet.2009.04.082
Gastric emptying of hexose sugars in healthy humans. Effects of osmolality and molecular structure A. GOPINATH 1,∗ , T. LITTLE 1 , A. MCGLONE 1 , E. PATEL 1 , D. LASSMAN 1 , S. RHODES 2 , J. MCLAUGHLIN 1 , D. THOMPSON 1 1 Manchester University, Manchester, United Kingdom 2 Salford Royal Hospital Trust, Manchester, United Kingdom It has been suggested that hexose sugars signal to the brain to slow gastric emptying (GE) via osmoreceptor stimulation in the small intestine; however, equi-osmolar glucose and fructose appear to empty differently, and large inter-individual differences in the responses to sugars are apparent. Therefore, we aimed to (i) examine the effects of hexose type as well as osmolality, on GE and (ii) determine whether GE responses were consistent within individuals. 23 healthy lean adults were studied to evaluate effects of 250, 500 and 1000 mOsmol solutions of glucose, galactose, fructose, and its poorly absorbed analogue, tagatose, using water, NaCl and lactulose as volumetric, and osmotic, controls. GE was assessed using a 13 C-acetate breath test. 3 subjects subsequently underwent 32 studies to evaluate intra-individual reproducibility. At 250 mOsmol, a sugar-specific effect was apparent: tagatose slowed GE (P < 0.05) compared with water, glucose and fructose. Fructose (P < 0.05), but not glucose and galactose, slowed GE but with substantial inter-individual differences in responsiveness. As the osmolality increased, GE of all hexoses was more potently slowed (P < 0.001), and the differences between them were abolished. 500 mOsmol solutions of lactulose and saline did not, whereas equi-osmolar solutions of glucose, fructose and tagatose did, slow GE when compared with water (P < 0.05). While inter-individual differences existed in the response to 250 mOsmol solutions of fructose, the response within an individual was consistent. While all hexose sugars slow GE at higher osmolarities, tagatose, and in some subjects, fructose, slowed GE more potently
than glucose or galactose at lower osmolality indicating that hexose-specific effects must operate on gut-to-brain signalling. doi:10.1016/j.appet.2009.04.083 Chronic sucrose intake reduces satiety-related activity in hypothalamic oxytocin neurons B.A. GOSNELL 1,∗ , P.K. OLSZEWSKI 2 , H.B. SCHIOTH 2 , M.K. GRACE 1 , A.S. LEVINE 1 1 University of Minnesota, St. Paul, MN, USA 2 Uppsala University, Uppsala, Sweden Oxytocin (OT) is one of many peptides thought to play a role in satiety. In light of the inhibitory effect of opioids on the activation of OT neurons, and the hypothesized role of opioids in mediating palatability, we measured whether long-term consumption of a sweet vs. a non-sweet diet would alter OT activity in a manner similar to that of opioids. Male rats were adapted to a food restriction regimen (2 h/day). Half the rats were given a sucrose-based diet for 20 days, while the other half was given a cornstarch-based diet (n = 14 per diet group). On the 21st day, half the rats in each group were given the opposite diet, and all diets were removed after 45 min. They were deeply anesthetized and perfused 60 min later. Double immunohistochemical staining (c-Fos and OT) was performed on coronal sections. The percentage of c-Fos positive OT cells in the PVN was significantly reduced in rats fed the sucrosebased diet, regardless of whether they received the sucrose or the cornstarch diet on day 21 (35.2 ± 3.5% for starch diet vs. 20.8 ± 2.7% for sucrose diet, p < 0.01). A similar pattern was observed in the supraoptic nucleus. This suggests that sucrose intake reduced activity in the OT system, and that the effect is not an acute effect of sucrose intake. The findings indicate that the consumption of sugar, in addition to providing taste reward, may also decrease activity in pathways that act as satiety systems. Decreased activity of satiety signals, therefore, could lead to overconsumption of foods other than sugar. Supported by NIH DA 021280. doi:10.1016/j.appet.2009.04.084 CD36 deletion is associated with decreased OEA production in the mouse small intestine A. GUIJARRO ∗ , J. FU, G. ASTARITA, D. PIOMELLI Department of Pharmacology, University of California, Irvine, Irvine, CA, USA Oleoylethanolamide (OEA) is a lipid-derived satiety factor produced by small intestinal enterocytes in response to fat ingestion. We previously showed that the fatty-acid transport protein CD36 plays a key role in mediating small-intestinal OEA biosynthesis following intra-duodenal fat infusion. Here we examined the impact of CD36 deletion on normal OEA production and feeding behavior in mice. Food intake (FI) was continuously analyzed in adult male CD36-null mice and wild-type C57BL/6J mice (WT) under free-feeding conditions for 12 consecutive days using an automated system. In a separate experiment, OEA levels were measured by LC/MS in a panel of tissues obtained from WT and CD36-null mice sacrificed during the dark or the light phase. OEA levels were lower in jejunum of CD36-null mice. No such difference was observed in other tissues, including duodenum, liver, fat and brain. No change was observed in the uptake of saturated or unsaturated fatty acids in duodenum and jejunum of null mice, compared to WT. Total FI was higher in CD36-null mice. This effect was observed mainly during the light phase and was associated with higher meal frequency and meal size and lower postmeal interval and satiety ratio. No genotype differences were found in plasma cholesterol, triacylglycerols, glucose, -hydroxybutyrate, leptin, adiponectin or insulin. These results support the hypothesis that CD36 contributes importantly to OEA production in the small intestine. The findings further suggest that CD36-null mice may have impaired satiety, which might be partly due to a decreased OEA signaling. doi:10.1016/j.appet.2009.04.085