Physiology: Does gut hormone PYY3–36 decrease food intake in rodents?

Tschöp, M.; Castañeda, Tamara R.; Joost, Hans-Georg; Thöne-Reineke, Christa; Ortmann, Sylvia; Schimrigk, К.; Hagan, Mary M.; Chandler, Paula C.; Oswald, Kimberly D.; Benoit, Stephen C.; Seeley, Randy J.; Kinzig, Kimberly P.; Moran, Timothy H.; Beck‐Sickinger, Annette G.; Koglin, Norman; Rodgers, R.J.; Blundell, John; Ishii, Yasuyuki; Beattie, A. H.; Holch, P; Allison, David B.; Raun, Kirsten; Madsen, Klavs; Wulff, Birgitte S.; Stidsen, Carsten E.; Birringer, Marc; Kreuzer, Oliver J.; Schindler, Marcus; Arndt, Kirsten; Rudolf, K; Michael, Mark; Dèng, Xiǎoyīng; Withcomb, D. C.; Halem, Heather; Taylor, John E.; Dong, Jiawen; Datta, Rakesh; Culler, Michael D.; Craney, S.; Flora, Daniel B.; Smiley, Dia; Heiman, Mark L.

doi:10.1038/nature02665a

Cited by 90 publications

(137 citation statements)

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“…Over the last few years much emphasis has been placed on the role of PYY, PPY and NPY2R in relation to obesity [6,12,16,22,28,33] in both humans and animal models. From the literature it has been demonstrated that NPY2R is a crucial receptor in appetite regulation.…”

Section: Discussionmentioning

confidence: 99%

“…Since then many studies have established the role of PYY in decreasing food intake in both animals [13][14][15][16][17][18] and humans [19][20][21]. However, contradictory evidence has also been presented, suggesting that PYY does not decrease food intake in rodents, further questioning its role as a potential anti-obesity drug target [22,23].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…The anorectic effect of PYY in humans has recently been questioned, however, since extensive efforts by independent groups have been unable to replicate the findings that PYY 3-36 decreases food intake in rodents [4] In addition, it has been suggested that PYY deficiency may be important in the pathogenesis of obesity, since obese persons were shown to have lower PYY levels than lean persons [3]. However, this has not been supported by the work of other investigators [5].…”

Section: Discussionmentioning

confidence: 99%

“…The physiology of PYY regulation and the potential efficacy of PYY as a therapeutic agent for obesity remain controversial, however, because recent extensive studies by independent groups of investigators have not been able to replicate the inhibitory effect of PYY on food intake in animals [4]. Moreover, the previously published data on PYY regulation in humans, including differences in PYY levels between lean and obese subjects [3] have not been replicated in a more recent study [5].…”

Section: Introductionmentioning

confidence: 99%

Peptide YY levels are decreased by fasting and elevated following caloric intake but are not regulated by leptin

et al. 2005

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Aims/hypothesis: Peptide YY (PYY) is a gutderived hormone that has been shown to reduce short-term food intake in animals and humans. It has been proposed that deficiency of PYY contributes to obesity in humans. However, the physiology of PYY regulation by factors such as caloric restriction, or by other molecules important in energy homeostasis, e.g. leptin, remains to be fully elucidated. Materials and methods: We evaluated the effect on PYY levels of: (1) caloric ingestion (a mixed meal) in five healthy normal-weight subjects; (2) fasting for 2 or 3 days in eight lean men and seven lean women respectively; and (3) recombinant human leptin administration at physiological replacement and pharmacological doses. Results: PYY levels increased 50% after a mixed meal (p=0.01), and shortterm complete fasting for 2 or 3 days decreased leptin and PYY levels to 20-30% and 40-60% of baseline, respectively (both p<0.05). However, recombinant human leptin administration at physiological doses to restore the fasting-induced decrease of leptin levels and at pharmacological doses over the short term had no effect on PYY levels. Conclusions/interpretation: PYY increases after meal ingestion and decreases after fasting in a manner consistent with a meal-related signal of energy homeostasis. Importantly, circulating levels of this gut-secreted molecule are independent of regulation by leptin over the short term. These findings contribute towards our understanding of the homeostatic systems that regulate appetite in humans, including the possible redundancy of gastrointestinally secreted and adipocyte-secreted signals. This may be of importance for the future development of medications to treat obesity.

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“…There has been controversy as to whether exogenously administered PYY reduces food intake in mice (Tschop et al, 2004). Moreover, there have been limitations in elevating PYY levels using osmotic mini-pumps because this mode of administration does not mimic the secretion of PYY in vivo ( Pittner et al, 2004).…”

Section: Attenuated Diet-induced Obesity In Pyytg Mice With No Effectmentioning

confidence: 99%

PYY transgenic mice are protected against diet-induced and genetic obesity

et al. 2008

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The gut-derived hormone, peptide YY (PYY) reduces food intake and enhances satiety in both humans and animals. Obese individuals also have a deficiency in circulating peptide YY, although whether this is a cause or a consequence of obesity is unclear. Our aims were to determine whether peptide YY (PYY) over-expression may have therapeutic effects for the treatment of obesity by altering energy balance and glucose homeostasis. We generated PYY transgenic mice and measured body weight, food intake, temperature, adiposity, glucose tolerance, circulating hormone and lipid concentrations and hypothalamic neuropeptide levels (neuropeptide Y; proopiomelanocortin, and thyrotropin-releasing hormone) under chow and high-fat feeding and after crossing these mice onto the genetically obese leptin-deficient ob/ob mouse background. PYY transgenic mice were protected against diet-induced obesity in association with increased body temperature (indicative of increased thermogenesis) and sustained expression of thyrotropin-releasing hormone in the paraventricular nucleus of the hypothalamus. Moreover, PYY transgenic mice crossed onto the genetically obese ob/ob background had significantly decreased weight gain and adiposity, reduced serum triglyceride levels and improved glucose tolerance compared to ob/ob controls. There was no effect of PYY transgenic over expression on basal or fastinginduced food intake measured at 11-12 weeks of age. Together, these findings suggest that long-term administration of PYY, PYY-like compounds or agents that stimulate PYY synthesis in vivo can reduce excess adiposity and improve glucose tolerance, possibly via effects on the hypothalamo-pituitary-thyroid axis and thermogenesis.

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Physiology: Does gut hormone PYY3–36 decrease food intake in rodents?

Cited by 90 publications

References 9 publications

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

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

Peptide YY levels are decreased by fasting and elevated following caloric intake but are not regulated by leptin

PYY transgenic mice are protected against diet-induced and genetic obesity

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