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Impaired gastric emptying using the 13C-octanoic breath test in rats with experimental spinal cord injury
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T.H. Moran / Appetite 51 (2010) 350–412
Effects of experimental spinal cord injury on food intake, body composition and gastrointestinal expression of CD36 mRNA in rats G.M. HOLMES ∗ , S.D. PRIMEAUX, M. TONG. Pennington Biomedical Research Center, Baton Rouge, USA
Modulation of the vomiting response in house musk shrews by food restriction C.C. HORN 1,∗ , C.E. FITZGERALD 2 , M.I. FRIEDMAN 1 . 1 Monell Chemical Senses Center, Philadelphia, USA 2 University of Pennsylvania, Philadelphia, USA
Failure to maintain body weight within prescribed ranges often occurs in humans with spinal cord injury (SCI). This population is also at risk for increased fat mass below the lesion. In rats with high (spinal T3) or low (spinal T9) SCI, we sought to identify shortterm derangements in feeding, body weight and fat mass. We also assayed gastrointestinal (GI) mRNA levels of the CD36 lipid transporter to begin to address diminished GI absorptive capacity. Daily body weight and mean energy intake (MEI) of low fat diet (28% protein, 13% fat, 59% carbohydrate) was collected for 3 weeks after SCI or sham surgery (n = 26). Body weight and MEI after sham surgery was significantly lower than preoperative baseline for only the first 24 h after surgery. Both T3 and T9 SCI suppressed postoperative body weight below baseline for 14 d and 12 d (respectively) while MEI remained below baseline for 7 d and 4 d (respectively). Animals with T9 SCI had significantly lower percentage of total fat pad weights (epididymal + retroperitoneal) than shams at 7 d post-SCI. Compared to shams, total fat pad weights were significantly lower in both 21 d T3 and T9 injured rats despite a significantly greater MEI. However, NMR analysis of the percentage of whole body fat mass was not significantly different. GI expression of CD36 mRNA was similar across 7 d survival groups, but was doubled in 21 d T3 SCI rats. This suggests that (1) body composition changes occur rapidly after SCI; (2) fat mass may redistribute through other tissues; (3) high thoracic SCI might alter nutrient absorption in the GI tract. doi:10.1016/j.appet.2008.04.117
Evidence suggests a significant interaction between neural circuits for feeding and emesis. For example, appetite stimulants, such as ghrelin and endocannabinoids, have been shown to be antiemetic. Here we tested the hypothesis that stimulation of “hunger” would increase the emetic threshold by assessing the effects of food restriction on emetic responses to nicotine in the house musk shrew. Unlike rodents, the shrew possesses a vomiting response and nicotine (2 mg/kg, sc) was determined to produce a consistent submaximal emetic response. Twenty-four hours, but not 3 h, of food restriction significantly increased food intake for 1 h upon refeeding. Furthermore, both 24 and 3 h of food restriction were sufficient to empty the gut of food but did not change % body fat. Twentyfour hours food-deprived animals showed fewer emetic responses (1.9 ± 0.8) than animals deprived for 3 h (6.6 ± 1.3). These results indicate that mild food restriction can significantly reduce emetic responses and highlights the close association between gut–brain systems controlling food intake and emesis. In a broader context, it might prove important to understand these interactions in order to control anorexia, emesis, and nausea in chronic diseases, such as late stage cancer. Acknowledgment: This work was supported by NIH grant DK065971. doi:10.1016/j.appet.2008.04.119
Impaired gastric emptying using the 13 C-octanoic breath test in rats with experimental spinal cord injury G.M. HOLMES ∗ , M. TONG, E.Q. CREEKMORE. Pennington Biomedical Research Center, Baton Rouge, USA Patients with spinal cord injuries (SCI) most often present reduced gastric emptying as well as a risk of reflux and aspiration of gastric contents. In an animal model of high thoracic SCI, gastric motility and reflex-evoked gastric relaxation is diminished 3 d post-injury. We tested the post-SCI changes in gastric emptying using the 13 C-octanoic breath test at 3, 7, 21 and 42 d in 16 h fasted rats that received either a control surgery without SCI, high (spinal T3) or low (spinal T9) SCI. Compared to surgical controls (n = 7), animals with complete T3 SCI (n = 6) or T9 SCI (n = 7) had significantly less percent recovery of 13 C substrate (86.6 ± 6.7% vs. 37.4 ± 4.1% or 48.5 ± 6.5%, respectively, p < 0.05) at 3 d. The peak recovery time (tlag ) was significantly different (84.5 ± 4.7 min vs. 52.5 ± 4.3 min or 69.8 ± 6.6 min, respectively, p < 0.05). Furthermore, half-emptying time (t1/2 ) was significantly shorter (129.7 ± 7.3 min vs. 68.2 ± 5.8 min or 93.1 ± 8.2 min, respectively, p < 0.05). This paradoxical acceleration of t1/2 may have been due to the 13 C substrate that remained unaccounted for at the termination of the 6 h test. Differences in 13 C percent recovery, tlag and t1/2 were all significant from surgical control at 7 and 21 d but not 42 d. These data demonstrate that gastric reflex function remains impaired at least 3 weeks after SCI. This dysfunction includes reduced levels of vagally dominated gastric motility and, possibility, gastric retention combined with pyloric sphincter dysfunction. The post-SCI suppression of these vago-vagal gastric reflexes suggests that SCI may interrupt ascending spinal afferent input to brainstem vagal nuclei. Acknowledgment: Support: NINDS #49177. doi:10.1016/j.appet.2008.04.118
Visfatin expression in brown adipose tissue of C57BL/6J mice 1 , A.K. PURHONEN 1 , J. ˆ A. HUOTARI 1,∗ , O. KYRYLENKO 1 , I. STUTZER WALKOWIAK 2 , K.H. HERZIG 1,3 . 1 A.I. Virtanen Institute, University of Kuopio, Finland 2 Poznan University of Medical Sciences, Poznan, Poland 3 Institute of Biomedicine, University of Oulu, Finland Visfatin is a novel member of the adipokine family and is identical to nicotinamide phosphoribosyltransferase (Nampt), an essential rate-limiting enzyme in biosynthesis of nicotinamide adenine dinucleotide (NAD+ ). Regulation of visfatin expression remains largely unknown. To study the regulation of visfatin in response to nutritional state, we examined expression levels of visfatin mRNA in fasted and fed mice. Three-month-old male C57BL/6J mice were fed ad libitum, or fasted 18 h and sacrificed. The mRNA expression was analyzed by real-time PCR. Protein levels were assessed by Western blotting. Visfatin mRNA in brown adipose tissue (BAT) was 10-fold higher compared to liver (p ≤ 0.001) and 2.5-fold higher than in visceral WAT. Visfatin mRNA was 2-fold higher in visceral than in subcutaneous WAT. The expression of visfatin in BAT was confirmed on protein level (4.8-fold higher compared to liver, p ≤ 0.01). Visfatin mRNA in BAT and liver was significantly increased by 2-fold and 1.6-fold (p ≤ 0.01 in both), respectively, after 18 h fasting, while mRNA in visceral or sc WAT did not change compared to fed mice. Visfatin is highly expressed in brown adipose tissue and protein levels and visfatin mRNA is upregulated in liver and BAT by fasting. As visfatin is a regulator of NAD+ synthesis and NAD+ substrate for sirtuins regulators of response to caloric restriction, the expression of visfatin in BAT might suggest a novel role of visfatin in the regulation of energy metabolism and thermogenesis. doi:10.1016/j.appet.2008.04.120
T.H. Moran / Appetite 51 (2010) 350–412
Effects of experimental spinal cord injury on food intake, body composition and gastrointestinal expression of CD36 mRNA in rats G.M. HOLMES ∗ , S.D. PRIMEAUX, M. TONG. Pennington Biomedical Research Center, Baton Rouge, USA
Modulation of the vomiting response in house musk shrews by food restriction C.C. HORN 1,∗ , C.E. FITZGERALD 2 , M.I. FRIEDMAN 1 . 1 Monell Chemical Senses Center, Philadelphia, USA 2 University of Pennsylvania, Philadelphia, USA
Failure to maintain body weight within prescribed ranges often occurs in humans with spinal cord injury (SCI). This population is also at risk for increased fat mass below the lesion. In rats with high (spinal T3) or low (spinal T9) SCI, we sought to identify shortterm derangements in feeding, body weight and fat mass. We also assayed gastrointestinal (GI) mRNA levels of the CD36 lipid transporter to begin to address diminished GI absorptive capacity. Daily body weight and mean energy intake (MEI) of low fat diet (28% protein, 13% fat, 59% carbohydrate) was collected for 3 weeks after SCI or sham surgery (n = 26). Body weight and MEI after sham surgery was significantly lower than preoperative baseline for only the first 24 h after surgery. Both T3 and T9 SCI suppressed postoperative body weight below baseline for 14 d and 12 d (respectively) while MEI remained below baseline for 7 d and 4 d (respectively). Animals with T9 SCI had significantly lower percentage of total fat pad weights (epididymal + retroperitoneal) than shams at 7 d post-SCI. Compared to shams, total fat pad weights were significantly lower in both 21 d T3 and T9 injured rats despite a significantly greater MEI. However, NMR analysis of the percentage of whole body fat mass was not significantly different. GI expression of CD36 mRNA was similar across 7 d survival groups, but was doubled in 21 d T3 SCI rats. This suggests that (1) body composition changes occur rapidly after SCI; (2) fat mass may redistribute through other tissues; (3) high thoracic SCI might alter nutrient absorption in the GI tract. doi:10.1016/j.appet.2008.04.117
Evidence suggests a significant interaction between neural circuits for feeding and emesis. For example, appetite stimulants, such as ghrelin and endocannabinoids, have been shown to be antiemetic. Here we tested the hypothesis that stimulation of “hunger” would increase the emetic threshold by assessing the effects of food restriction on emetic responses to nicotine in the house musk shrew. Unlike rodents, the shrew possesses a vomiting response and nicotine (2 mg/kg, sc) was determined to produce a consistent submaximal emetic response. Twenty-four hours, but not 3 h, of food restriction significantly increased food intake for 1 h upon refeeding. Furthermore, both 24 and 3 h of food restriction were sufficient to empty the gut of food but did not change % body fat. Twentyfour hours food-deprived animals showed fewer emetic responses (1.9 ± 0.8) than animals deprived for 3 h (6.6 ± 1.3). These results indicate that mild food restriction can significantly reduce emetic responses and highlights the close association between gut–brain systems controlling food intake and emesis. In a broader context, it might prove important to understand these interactions in order to control anorexia, emesis, and nausea in chronic diseases, such as late stage cancer. Acknowledgment: This work was supported by NIH grant DK065971. doi:10.1016/j.appet.2008.04.119
Impaired gastric emptying using the 13 C-octanoic breath test in rats with experimental spinal cord injury G.M. HOLMES ∗ , M. TONG, E.Q. CREEKMORE. Pennington Biomedical Research Center, Baton Rouge, USA Patients with spinal cord injuries (SCI) most often present reduced gastric emptying as well as a risk of reflux and aspiration of gastric contents. In an animal model of high thoracic SCI, gastric motility and reflex-evoked gastric relaxation is diminished 3 d post-injury. We tested the post-SCI changes in gastric emptying using the 13 C-octanoic breath test at 3, 7, 21 and 42 d in 16 h fasted rats that received either a control surgery without SCI, high (spinal T3) or low (spinal T9) SCI. Compared to surgical controls (n = 7), animals with complete T3 SCI (n = 6) or T9 SCI (n = 7) had significantly less percent recovery of 13 C substrate (86.6 ± 6.7% vs. 37.4 ± 4.1% or 48.5 ± 6.5%, respectively, p < 0.05) at 3 d. The peak recovery time (tlag ) was significantly different (84.5 ± 4.7 min vs. 52.5 ± 4.3 min or 69.8 ± 6.6 min, respectively, p < 0.05). Furthermore, half-emptying time (t1/2 ) was significantly shorter (129.7 ± 7.3 min vs. 68.2 ± 5.8 min or 93.1 ± 8.2 min, respectively, p < 0.05). This paradoxical acceleration of t1/2 may have been due to the 13 C substrate that remained unaccounted for at the termination of the 6 h test. Differences in 13 C percent recovery, tlag and t1/2 were all significant from surgical control at 7 and 21 d but not 42 d. These data demonstrate that gastric reflex function remains impaired at least 3 weeks after SCI. This dysfunction includes reduced levels of vagally dominated gastric motility and, possibility, gastric retention combined with pyloric sphincter dysfunction. The post-SCI suppression of these vago-vagal gastric reflexes suggests that SCI may interrupt ascending spinal afferent input to brainstem vagal nuclei. Acknowledgment: Support: NINDS #49177. doi:10.1016/j.appet.2008.04.118
Visfatin expression in brown adipose tissue of C57BL/6J mice 1 , A.K. PURHONEN 1 , J. ˆ A. HUOTARI 1,∗ , O. KYRYLENKO 1 , I. STUTZER WALKOWIAK 2 , K.H. HERZIG 1,3 . 1 A.I. Virtanen Institute, University of Kuopio, Finland 2 Poznan University of Medical Sciences, Poznan, Poland 3 Institute of Biomedicine, University of Oulu, Finland Visfatin is a novel member of the adipokine family and is identical to nicotinamide phosphoribosyltransferase (Nampt), an essential rate-limiting enzyme in biosynthesis of nicotinamide adenine dinucleotide (NAD+ ). Regulation of visfatin expression remains largely unknown. To study the regulation of visfatin in response to nutritional state, we examined expression levels of visfatin mRNA in fasted and fed mice. Three-month-old male C57BL/6J mice were fed ad libitum, or fasted 18 h and sacrificed. The mRNA expression was analyzed by real-time PCR. Protein levels were assessed by Western blotting. Visfatin mRNA in brown adipose tissue (BAT) was 10-fold higher compared to liver (p ≤ 0.001) and 2.5-fold higher than in visceral WAT. Visfatin mRNA was 2-fold higher in visceral than in subcutaneous WAT. The expression of visfatin in BAT was confirmed on protein level (4.8-fold higher compared to liver, p ≤ 0.01). Visfatin mRNA in BAT and liver was significantly increased by 2-fold and 1.6-fold (p ≤ 0.01 in both), respectively, after 18 h fasting, while mRNA in visceral or sc WAT did not change compared to fed mice. Visfatin is highly expressed in brown adipose tissue and protein levels and visfatin mRNA is upregulated in liver and BAT by fasting. As visfatin is a regulator of NAD+ synthesis and NAD+ substrate for sirtuins regulators of response to caloric restriction, the expression of visfatin in BAT might suggest a novel role of visfatin in the regulation of energy metabolism and thermogenesis. doi:10.1016/j.appet.2008.04.120