Intermittent intraperitoneal infusion of peptide YY(3-36) reduces daily food intake and adiposity in obese rats

2007 ◽  
Vol 293 (1) ◽  
pp. R39-R46 ◽  
Author(s):  
Prasanth K. Chelikani ◽  
Alvin C. Haver ◽  
Roger D. Reidelberger

Peptide YY(3-36) [PYY(3-36)] is a gut-brain peptide that decreases food intake when administered by intravenous infusion to lean and obese humans and rats. However, chronic administration of PYY(3-36) by osmotic minipump to lean and obese rodents produces only a transient reduction in daily food intake and weight gain. It has recently been shown that 1-h intravenous infusions of PYY(3-36) every other hour for 10 days produced a sustained reduction in daily food intake, body weight, and adiposity in lean rats. Here, we determined whether intermittent delivery of PYY(3-36) can produce a similar response in diet-induced obese rats. During a 21-day period, obese rats (body fat >25%) received twice daily intraperitoneal infusion of vehicle ( n = 18) or PYY(3-36) ( n = 24) during hours 1–3 and 7–9 of the dark period. Rats had free access to both a 45% fat solid diet and a 29% fat liquid diet; intakes were determined from continuous computer recording of changes in food container weights. To sustain a 15–25% reduction in daily caloric intake, the initial PYY(3-36) dose of 30 pmol·kg−1·min−1 was reduced to 10 pmol·kg−1·min−1 on day 10 and then increased to 17 pmol·kg−1·min−1 on day 13. This dosing strategy produced a sustained reduction in daily caloric intake of 11–32% and prevented body weight gain (8 ± 6 vs. 51 ± 11 g) and fat deposition (4.4 ± 7.6 vs. 41.0 ± 12.8 g). These results indicate that intermittent intraperitoneal infusion of PYY(3-36) can produce a sustained reduction in food intake and adiposity in diet-induced obese rodents consuming palatable high-fat foods.

2007 ◽  
Vol 293 (5) ◽  
pp. R1798-R1808 ◽  
Author(s):  
Prasanth K. Chelikani ◽  
Alvin C. Haver ◽  
Roger D. Reidelberger

Chronic administration of anorexigenic substances to experimental animals by injections or continuous infusion typically produces no effect or a transient reduction in daily food intake and body weight. Our aim was to identify an intermittent dosing strategy for intraperitoneal infusion of salmon calcitonin (sCT), a homolog of amylin that produces a sustained 25–35% reduction in daily food intake and adiposity in diet-induced obese rats. Rats (649 ± 10 g body wt, 27 ± 1% body fat), with intraperitoneal catheters tethered to infusion swivels, had free access to a 45% fat diet. Food intake, body weight, and adiposity during the 7-wk test period were relatively stable in the vehicle-treated rats ( n = 16). None of 10 sCT dosing regimens administered in succession to a second group of rats ( n = 18) produced a sustained 25–35% reduction in daily food intake for >5 days, although body weight and adiposity were reduced by 9% (587 ± 12 vs. 651 ± 14 g) and 22% (20.6 ± 1.2 vs. 26.5 ± 1.1%), respectively, across the 7-wk period. The declining inhibitory effect of sCT on daily food intake with the 6-h interinfusion interval appeared to be due in part to an increase in food intake between infusions. The declining inhibitory effect of sCT on daily food intake with the 2- to 3-h interinfusion interval suggested possible receptor downregulation and tolerance to frequent sCT administration; however, food intake increased dramatically when sCT was discontinued for 1 day after apparent loss of treatment efficacy. Together, these results demonstrate the activation of a potent homeostatic response to increase food intake when sCT reduces food intake and energy reserves in diet-induced obese rats.


2006 ◽  
Vol 290 (2) ◽  
pp. R298-R305 ◽  
Author(s):  
Prasanth K. Chelikani ◽  
Alvin C. Haver ◽  
Joseph R. Reeve ◽  
David A. Keire ◽  
Roger D. Reidelberger

The gut hormone peptide YY(3-36) [PYY(3-36)] decreases food intake when administered by intravenous infusion to lean and obese humans and rats. Whether chronic administration of PYY(3-36) produces a sustained reduction in food intake and adiposity is the subject of intense debate. Batterham et al. (R. L. Batterham, M. A. Cowley, C. J. Small, H. Herzog, M. A. Cohen, C. L. Dakin, A. M. Wren, A. E. Brynes, M. J. Low, M. A. Ghatei, R. D. Cone, and S. R. Bloom. Nature 418: 650–654, 2002) first reported that PYY(3-36) reduces food intake and weight gain in rats when injected into the peritoneal cavity twice daily for 7 days. Numerous laboratories have failed to confirm that daily injections of PYY(3-36) decrease body weight. Continuous subcutaneous administration of PYY(3-36) by osmotic minipump has been reported to reduce daily food intake in rodents but only during the first 3–4 days of administration. Here we show the effects of different daily patterns of intravenous infusion of PYY(3-36) on food intake, body weight, and adiposity in rats tethered via infusion swivels to computer-controlled pumps. Measurement of food bowl weight recorded by computer every 20 s permitted daily assessment of the instantaneous effects of PYY(3-36) administration on food intake and meal patterns. One-hour intravenous infusions of PYY(3-36) at 30 pmol·kg−1·min−1 every other hour for 10 days produced a sustained reduction in daily food intake of ∼20% and decreased body weight and adiposity by 7 and 35%, respectively. Thus dosage pattern is critical for producing a sustained effect of PYY(3-36) on food intake and adiposity.


2008 ◽  
Vol 295 (2) ◽  
pp. R449-R458 ◽  
Author(s):  
Roger D. Reidelberger ◽  
Alvin C. Haver ◽  
Prasanth K. Chelikani ◽  
James L. Buescher

Chronic administration of anorexigenic substances to experimental animals by injections or continuous infusion typically produces either no effect or a transient reduction in food intake and body weight. Our aim here was to identify an intermittent dosing strategy for intraperitoneal infusion of peptide YY(3-36) [PYY(3-36)] that produces a sustained reduction in daily food intake and adiposity in diet-induced obese rats. Rats (665 ± 10 g body wt, 166 ± 7 g body fat) with intraperitoneal catheters tethered to infusion swivels had free access to a high-fat diet. Vehicle-treated rats ( n = 23) had relatively stable food intake, body weight, and adiposity during the 9-wk test period. None of 15 PYY(3-36) dosing regimens administered in succession to a second group of rats ( n = 22) produced a sustained 15–25% reduction in daily food intake for >5 days, although body weight and adiposity were reduced across the 9-wk period by 12% (594 ± 15 vs. 672 ± 15 g) and 43% (96 ± 7 vs. 169 ± 9 g), respectively. The declining inhibitory effect of PYY(3-36) on daily food intake when the interinfusion interval was ≥3 h appeared to be due in part to an increase in food intake between infusions. The declining inhibitory effect of PYY(3-36) on daily food intake when the interinfusion interval was < 3 h suggested possible receptor downregulation and tolerance to frequent PYY(3-36) administration; however, food intake significantly increased when PYY(3-36) treatments were discontinued for 1 day following apparent loss in treatment efficacies. Together, these results demonstrate the development of a potent homeostatic response to increase food intake when PYY(3-36) reduces food intake and energy reserves in diet-induced obese rats.


Parasitology ◽  
1981 ◽  
Vol 82 (1) ◽  
pp. 23-38 ◽  
Author(s):  
D. W. T. Crompton ◽  
D. E. Walters ◽  
Susan Arnold

SUMMARYThe daily food intake and related changes in body weight were measured in young rats which were fed on synthetic diets containing 1% (3 experiments), 2% (4 experiments) and 20% (1 experiment) casein respectively. Some rats were infected with Nippostrongylus brasiliensis and allowed to feed ad libitum, some remained uninfected and were allowed to feed ad libitum while others, which were matched by initial weight with rats from the infected group, remained uninfected and were given only the same amount of food as that consumed during the previous 24 h by their infected partners. No significant differences were detected between the rats before the start of the infection. Thereafter, the food intake of the infected undernourished rats was usually found to be significantly lower and the loss of body weight significantly greater than those of the uninfected rats. In infection periods of relatively long duration, the pair-fed uninfected rats did not lose as much weight as their infected partners even though their food intake (1% and 2% casein) was the same. Although the food intake, and consequently the weight, of infected rats fed on the diet containing 20% casein were significantly less than in their uninfected partners, no significant differences were observed between the weights of the infected and pair-fed rats fed on this diet.


2004 ◽  
Vol 287 (5) ◽  
pp. R1044-R1053 ◽  
Author(s):  
Michael M. Chi ◽  
Guoping Fan ◽  
Edward A. Fox

Neurotrophin-4 (NT-4) knockout mice exhibited decreased innervation of the small intestine by vagal intraganglionic laminar endings (IGLEs) and reduced food satiation. Recent findings suggested this innervation was increased in NT-4 knock-in (NT-4KI) mice. Therefore, to further investigate the relationship between intestinal IGLEs and satiation, meal patterns were characterized using solid and liquid diets, and cholecystokinin (CCK) effects on 30-min solid diet intake were examined in NT-4KI and wild-type mice. NT-4KI mice consuming the solid diet exhibited reduced meal size, suggesting increased satiation. However, compensation occurred through increased meal frequency, maintaining daily food intake and body weight gain similar to controls. Mutants fed the liquid diet displayed a decrease in intake rate, again implying increased satiation, but meal duration increased, which led to an increase in meal size. This was compensated for by decreased meal frequency, resulting in similar daily food intake and weight gain as controls. Importantly, these alterations in NT-4KI mice were opposite, or different, from those of NT-4 knockout mice, further supporting the hypothesis that they are specific to vagal afferent signaling. CCK suppressed short-term intake in mutants and controls, but the mutants exhibited larger suppressions at lower doses, implying they were more sensitive to CCK. Moreover, devazepide prevented this suppression, indicating this increased sensitivity was mediated by CCK-1 receptors. These results suggest that the NT-4 gene knock-in, probably involving increased intestinal IGLE innervation, altered short-term feeding, in particular by enhancing satiation and sensitivity to CCK, whereas long-term control of daily intake and body weight was unaffected.


1984 ◽  
Vol 38 (3) ◽  
pp. 323-340 ◽  
Author(s):  
R. B. Thiessen ◽  
Eva Hnizdo ◽  
D. A. G. Maxwell ◽  
D. Gibson ◽  
C. S. Taylor

ABSTRACTA multibreed cattle experiment involving 25 British breeds was set up to study genetic variation between breeds and genetic inter-breed relationships for a wide spectrum of traits in order to examine the problems of between-breed testing and selection. The experimental design is described and results on between-breed variation are presented for four traits.All animals were housed indoors and from 12 weeks of age were given a single complete pelleted diet ad libitum through a system of Calan-Broadbent electronic gates. Females were mated to produce one purebred and three crossbred calves, which were reared to slaughter in order to measure the efficiency of the cow-calf unit of production.Results based on a total of 292 animals, with an average of 12 per breed, are presented for body weight, cumulated voluntary food intake, daily weight gain and daily food intake over the age range from 12 to 72 weeks. The 25 breed-mean curves for body weight and cumulated food intake displayed a remarkably uniform pattern of rankings at all ages and the rankings were very similar for both traits.The multibreed design used was effective in estimating between-breed variation as a proportion of total variation for the four traits examined. After approximately 1 year of age, the proportion of variation between breeds was approximately 0·70 for body weight and 0·60 for cumulated voluntary food intake. Changes in these traits could therefore be brought about more effectively by selection between breeds rather than within breeds. For average daily weight gain measured over 12-week intervals, between-breed selection was estimated to be most effective in the period of maximum growth rate between 6 and 9 months of age, when between-breed variation was 0·52 of the total. For average daily food intake, measured over 12-week intervals, between-breed selection was likely to be effective beyond 6 months of age, when the proportion of between-breed variation plateaued at 0·48.At all ages, the coefficient of genetic variation between breeds was approximately 0·14 for body weight and daily gain, and remarkably constant at approximately 0·12 for both daily and cumulated food intake. It is suggested that, for growth and intake traits, the genetic variances within and between breeds remain proportional to each other at all ages.


2006 ◽  
Vol 82 (1) ◽  
pp. 7-12 ◽  
Author(s):  
N. H. Nguyen ◽  
C. P. McPhee ◽  
C. M. Wade

AbstractThe objective of this study was to examine genetic changes in reproduction traits in sows (total number born (TNB), number born alive (NBA), average piglet birth weight (ABW) and number of piglets weaned (NW), body weight prior to mating (MW), gestation length (GL) and daily food intake during lactation (DFI)) in lines of Large White pigs divergently selected over 4 years for high and low post-weaning growth rate on a restricted ration. Heritabilities and repeatabilities of the reproduction traits were also determined. The analyses were carried out on 913 litter records using average information-restricted maximum likelihood method applied to single trait animal models. Estimates of heritability for most traits were small, except for ABW (0·33) and MW (0·35). Estimates of repeatability were slightly higher than those of heritability for TNB, NBA and NW, but they were almost identical for ABW, MW, GL and DFI. After 4 years of selection, the high growth line sows had significantly heavier body weight prior to mating and produced significantly more piglets born alive with heavier average birth weight than the low line sows. There were, however, no statistical differences between the selected lines in TNB or NW. The lower food intake of high relative to low line sows during lactation was not significant, indicating that daily food intake differences found between grower pigs in the high and low lines (2·71 v. 2·76 kg/day, s.e.d. 0·024) on ad libitum feeding were not fully expressed in lactating sows. It is concluded that selection for growth rate on the restricted ration resulted in beneficial effects on important measures of reproductive performance of thea sows.


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