How does PYY 3-36 improve glucose tolerance?

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Abstracts

4.6 ± 0.81). We observed a positive correlation for NPY4R copy number and BMI (r = 0.265, p b 0.001) and for NPY4R copy number and waist circumference (r = 0.264, p b 0.001). Linear regression analysis suggests that each additional copy of NPY4R leads to 2.87 kg/m2 increase in BMI and 6.05 cm in waist circumference for the whole sample (p b 0.001) and 3.7 kg/m2 increase in BMI and 8.12 cm in waist circumference for women (p b 0.001). We did not detect any correlation between NPY4R copy number and total energy intake; however, we observed a weak negative correlation between NPY4R copy number and energy intake from desserts in women (r = −141, p = 0.013). These data suggest that the role of NPY4R and pancreatic polypeptide in the regulation of body weight may need to be reconsidered. Acknowledgements: This work was supported by a grant from the Swedish Research Council.

References

Jarick, et al., 2011. Hum. Mol. Genet. 20, 840–852. Sha, et al., 2009. J. Hum. Genet. 54, 199–202. Sun, et al., 2013. Gene 516, 198–203.

doi:10.1016/j.npep.2015.11.078

SESSION 14 FEEDING AND OBESITY I ? (IN COLLABORATION WITH CRC 1052 OBESITY MECHANISMS) HOW DOES PYY 3-36 IMPROVE GLUCOSE TOLERANCE? Michael A Cowley, Stephanie E. Simonds; Department of Physiology, Monash University, VIC, Australia The role of NPY and PYY in the regulation of feeding is well documented, NPY acts via pathways in the hypothalamus to increase food intake and decrease energy expenditure. We have previously reported that PYY3-36 also acts via hypothalamic pathways to reduce food intake, although this has been disputed. It has also recently been shown that PYY3-36 can improve glucose tolerance, here we sought to determine how this effect occur. Mice were treated intraperitoneally with PYY3-36, and blood glucose measured during a glucose tolerance test (GTT). As previously shown, peripheral PYY3-36 improved glucose tolerance, leading to lower glucose levels during a GTT. We selectively expressed a modified glycine channel in AgRP/NPY neurons of the arcuate nucleus. This channel is engineered to bind to and be opened by a novel pharmacophore, PSEM, and no longer respond to glycine; thus we were able to pharmacologically inhibit the AgRP/NPY neurons. The effect of PYY3-36 on glucose tolerance was mediated, at least in part, by AgRP/NPY neurons, because when we pharmacologically silenced those neurons, PYY3-36 no longer improved glucose tolerance. This work shows the rapid effect of the brain on glucose homeostasis in rodents, and suggests new roles for NPY/PYY peptides in the regulation of blood glucose. This work was supported by the Australian NHMRC and National Heart Foundation.

doi:10.1016/j.npep.2015.11.079

GHRELIN AND PYY IN BARIATRIC SURGERY Chih-Yen Chena,b,, Haruka Amitanic, Akio Inuic; aFaculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; b Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; cDepartment of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan Bariatric surgery has become a new strategy for treatment of obesity and type 2 diabetes mellitus. Besides the calorie restriction and malabsorption, alterations in hormonal profile, especially gut-derived hormones, play important roles in regulation of body weight, energy homeostasis, and glycemic control. Among various gastrointestinal hormones, ghrelin and peptide YY are well-investigated after bariatric surgery in animal models and clinical trials. In this talk, we collect studies from clinical trials and focus on the comparison between different surgical types, such as Rux-en-Y gastric bypass, sleeve gastrectomy, adjustable gastric banding, and biliopancreatic diversion. The effectiveness of these surgeries on body weight loss, glycemic control, and changes in ghrelin and PYY regulation will be discussed. Although there are varieties of outcomes from different investigations, all bariatric surgeries lead to body weight loss and improvement of glycemic homeostasis, whereas the effectiveness depends on the surgical types. Fasting ghrelin and PYY levels changes in different manners between different surgeries, but in restoration of physiological hormonal responses after meal is the most important mechanism which correlates with improvement of obesity and metabolism. In conclusion, bariatric surgeries are effective treatment for obesity and type 2 diabetes mellitus compared with conventional medical treatment. The advantages of surgical treatment over medical treatment may be the consequence of normalization of physiological gut hormonal responses after meal. The results also provide information of physiological energy metabolism and new insight into the management of metabolic disorders. Acknowledgements: This research was supported in part by the Taiwan Ministry of Science and Technology (MOST 103-2314B-010-011-). References

Chen, C.Y., et al., 2012. Curr. Pharm. Des. 18, 4755–4765. Chen, C.Y., et al., 2013. Curr. Pharm. Des. 19, 5830–5835. Lee, W.J., et al., 2011. Surg. Obes. Relat. Dis. 7, 683–690. doi:10.1016/j.npep.2015.11.080

NPY OVEREXPRESSION IN NTS INDUCES HYPERPHAGIA AND ATTENUATES SYMPATHETIC TONE Liisa Ailanena,, Kim Eerolaa, Laura Vähätaloa, Jaakko Koprab, Minttu Mattilaa, Suvi Ruohonena, Eriika Savontausa; aDepartment of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland; bFaculty of Pharmacy, Division of Pharmacology and Pharmacotherapy, University of Helsinki, Finland The role of NPY overexpression in central noradrenergic neurons to the development of the metabolic syndrome was studied by stereotactic injection of NPY gene containing lentivirus into the locus coeruleus (LC) or nucleus tractus solitarius (NTS) in the brainstem of C57BL/6N mice (n = 8–12). The reporter gene EGFP containing virus was used as control. Food intake on a chow diet and weight gain of mice housed a