Characterization of the effects of pancreatic polypeptide in the regulation of energy balance

Asakawa, Akihiro; Inui, Akio; Yuzuriha, H; Ueno, Naohiko; Katsuura, Goro; Fujimiya, Mineko; Fujino, Masayuki; Niijima, Akira; Meguid, Michael M.; Kasuga, Masato

doi:10.1016/s0016-5085(03)00216-6

Cited by 312 publications

(249 citation statements)

References 30 publications

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“…In addition to their respective binding to the Y4 and Y2 receptors, human PP and PYY 3À36 have significant binding affinity for the appetite-stimulatory Y5 receptor. 10,16 Theoretically, Y5 receptor stimulation could act to oppose the appetite inhibition associated with the Y2 and Y4 receptors. In the human study, energy intake was statistically greater following the combined PP þ PYY infusion compared with PP infusion alone.…”

Section: Discussionmentioning

confidence: 99%

“…8 In addition to their central actions, PP and PYY may also inhibit food intake through a reduction in gut motility. 9,10 There is evidence that co-administration of appetiterelated peptides may inhibit feeding synergistically. The gut hormone cholecystokinin-8 (CCK-8) potentiated the appetite inhibitory effects of the adipocyte hormone, leptin, in rodents.…”

Section: Introductionmentioning

confidence: 99%

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No evidence of an additive inhibitory feeding effect following PP and PYY3−36 administration

et al. 2008

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Pancreatic polypeptide (PP) and peptide YY (PYY) are released by the gut in response to nutrients and inhibit food intake in rodents and humans. We hypothesized that PP and PYY 3À36 would inhibit feeding additively. Fasted male C57BL/6 mice were injected intraperitoneally with saline, PP, PYY 3À36 or PP þ PYY 3À36 (n ¼ 7-10). Food intake at 1 h was significantly inhibited by 6 nmol kg À1 PP and by 6 nmol kg À1 PYY 3-36 (Po0.05) but not significantly following 3 nmol kg À1 PP þ 3 nmol kg À1 PYY 3À36 . In a higher dose study 30 nmol kg À1 PP, 30 nmol kg À1 PYY 3À36 and 30 nmol kg À1 PP þ 30 nmol kg À1 PYY 3À36 all inhibited 1 h food intake compared with saline (Po0.05) but there was no significant difference in the food intake of the combined group compared with either hormone individually. Subsequently, 16 fasted lean healthy human volunteers (6 men and 10 women) received, in random order, 90 min intravenous infusions of saline, 4 pmol kg À1 min À1 PP, 0.4 pmol kg À1 min À1 PYY 3À36 and 4 pmol kg À1 min À1 PP þ 0.4 pmol kg À1 min À1 PYY 3À36 . A pasta lunch was served 60 min following infusion. There was no evidence of a greater decrease in food intake with the combined PP þ PYY 3À36 treatment (buffet meal energy intake (KJ): saline 2633 ± 204, PP þ PYY 2693 ± 254, PP 2367 ± 199, PYY 2511 ± 196). These results suggest that PP and PYY 3À36 do not inhibit feeding additively in rodents or humans.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

No evidence of an additive inhibitory feeding effect following PP and PYY3−36 administration

et al. 2008

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“…Pancreatic polypeptide (PP), released from F-cells of the pancreatic islets in response to food intake, plays an important role in the control of food intake and long-term energy balance , Batterham et al, 2003and Asakawa et al, 2003. PP dose-dependently reduces food intake in freely fed and fasted mice, and this is mediated through the Y4 receptor since the effect is abolished in Y4 receptor knockout mice (Balasubramaniam et al, 2006 andLin et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…Y4 agonism with PP is thought to mediate effects on appetite and energy balance by actions within the brainstem, resulting in modulation of digestive processes such as gastric secretion, motility and emptying by modulating vagal cholinergic pathways , Asakawa et al, 2003, McTigue et al, 1997and Adrian et al, 1976. Besides indirect effects via the brain stem on gastrointestinal functions, the hypothalamus also appears to be involved in mediating PP's effects on food intake.…”

Section: Introductionmentioning

confidence: 99%

Y4 receptors and pancreatic polypeptide regulate food intake via hypothalamic orexin and brain-derived neurotropic factor dependent pathways

et al. 2010

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Gut-derived peptides are known to regulate food intake by activating specific receptors in the brain, but the target nuclei and neurons influenced are largely unknown. Here we show that peripherally administered pancreatic polypeptide (PP) stimulates neurons in key nuclei of the hypothalamus critical for appetite and satiety regulation. In the lateral hypothalamic area (LHA), also known as the feeding center, neurons expressing the orexigenic neuropeptide orexin co-localize with the early neuronal activation marker c-Fos upon i.p. injection of PP into mice. In the ventromedial hypothalamus (VMH), also known as the satiety center, neurons activated by PP, as indicated by induction of c-Fos immunoreactivity, express the anorexigenic brain-derived neurotrophic factor (BDNF). Activation of neurons in the LHA and VMH in response to PP occurs via a Y4 receptor-dependent process as it is not seen in Y4 receptor knockout mice. We further demonstrate that in response to i.p. PP, orexin mRNA expression in the LHA is down-regulated, with Y4 receptors being critical for this effect as it is not seen in Y4 receptor knockout mice, whereas BDNF mRNA expression is up-regulated in the VMH in response to i.p. PP in the fasted, but not in the non-fasted state. Taken together these data suggest that PP can regulate food intake by suppressing orexigenic pathways by down-regulation of orexin and simultaneously increasing anorexigenic pathways by upregulating BDNF.

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“…PPY is reported to inhibit food intake and stimulate energy expenditure following its peripheral administration [30]. It has been shown that children with Prader-Willi syndrome have decreased secretion of PPY [31] and that peripheral administration of PPY leads to a decrease in food intake in rodents [32].…”

Section: Introductionmentioning

confidence: 99%

Single nucleotide polymorphisms in the neuropeptide Y2 receptor (NPY2R) gene and association with severe obesity in French white subjects

et al. 2007

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Aims/hypothesis Genetic variants of genes for peptide YY (PYY), neuropeptide Y2 receptor (NPY2R) and pancreatic polypeptide (PPY) were investigated for association with severe obesity. Subjects and methods The initial screening of the genes for variants was performed by sequencing in a group of severely obese subjects (n=161). Case-control analysis of the common variants was then carried out in 557 severely obese adults, 515 severely obese children and 1,163 nonobese/non-diabetic control subjects. Rare variants were genotyped in 700 obese children and the non-obese/nondiabetic control subjects (n=1,163). Results Significant association was found for a 5′ variant (rs6857715) in the NPY2R gene with both severe adult obesity (p=0.002) and childhood obesity (p=0.02). This significant association was further supported by a pooled allelic analysis of all obese cases (adults and children, n=928) vs the control subjects (n=938) (p=0.0004, odds ratio=1.3, 95% CI 1.1-1.5). Quantitative trait analysis of BMI and WHR was performed and significant association was observed for SNP rs1047214 in NPY2R with an increase in WHR in the severely obese children (codominant model p=0.005, recessive model p=0.001). Association was also observed for an intron 3 variant (rs162430) in the PYY gene with childhood obesity (p=0.04). No significant associations were observed for PPY variants. Only one rare variant in the NPY2R gene (C-5641T) was not found in lean individuals and this was found to co-segregate with obesity in one family. Conclusions/interpretation These results provide evidence of association for NPY2R and PYY gene variants with obesity and none for PPY variants. A rare variant of the NPY2R gene showed evidence of co-segregation with Diabetologia (2007)

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Characterization of the effects of pancreatic polypeptide in the regulation of energy balance

Cited by 312 publications

References 30 publications

No evidence of an additive inhibitory feeding effect following PP and PYY3−36 administration

No evidence of an additive inhibitory feeding effect following PP and PYY3−36 administration

Y4 receptors and pancreatic polypeptide regulate food intake via hypothalamic orexin and brain-derived neurotropic factor dependent pathways

Single nucleotide polymorphisms in the neuropeptide Y2 receptor (NPY2R) gene and association with severe obesity in French white subjects

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