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Laurentiu M Pop, Andrea Mari, Tong-Jin Zhao, Lori Mitchell, Shawn Burgess, Xilong Li, Beverley Adams-Huet, Ildiko Lingvay
AIM: To investigate the physiological mechanisms leading to rapid improvement in diabetes after Roux-en-Y Gastric Bypass (RYGB). In particular, the roles of concurrent peri-operative dietary restrictions, which may also alter glucose metabolism, have not been completely elucidated. MATERIALS AND METHODS: To assess the differential contributions of diet and surgery to the mechanisms leading to the rapid improvement in diabetes after RYGB we enrolled ten patients with type 2 diabetes scheduled to undergo RYGB...
March 13, 2018: Diabetes, Obesity & Metabolism
Anton M Pluschke, Barbara A Williams, Dagong Zhang, Stephen T Anderson, Eugeni Roura, Michael J Gidley
Acute and sustained soluble dietary fibre (SDF) consumption are both associated with improved glucose tolerance in humans and animal models (e.g. porcine). However, the effects on glucose tolerance in grower pigs, adapted to diets with a combination of SDF have not been studied previously. In this experiment, cereal SDF wheat arabinoxylan (AX) and oat β-glucan (BG) were fed individually and in combination to determine the effect on glucose tolerance in jugular vein catheterized grower pigs. Five groups of Large White male grower pigs were fed highly digestible diets containing either 10% AX, 10% BG, 5% AX with 5% BG, a model cereal whole wheat flour (WWF), or a control wheat starch diet (WS) with no SDF...
2018: PloS One
Charlotte Bayer Christiansen, Maria Buur Nordskov Gabe, Berit Svendsen, Lars Ove Dragsted, Mette Marie Rosenkilde, Jens J Holst
The colonic epithelium harbors a large number of endocrine cells, but little is known about the endocrine functions of the colon. However, the high density of GLP-1 and PYY secreting L-cells is of great interest because of the potential anti-diabetic and anti-obesity effects of GLP-1 and PYY. Short chain fatty acids (SCFAs) produced by local bacterial fermentation are suggested to activate the colonic free fatty acid receptors FFAR2 (GPR43) and FFAR3 (GPR41), stimulating the colonic L-cells. We used the isolated perfused rat colon as a model of colonic endocrine secretion and studied the effects of the predominant SCFAs formed: acetate, propionate and butyrate...
March 1, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Oleg G Chepurny, Ron L Bonaccorso, Colin A Leech, Torsten Wöllert, George M Langford, Frank Schwede, Christian L Roth, Robert P Doyle, George G Holz
We report the design and target validation of chimeric peptide EP45, a novel 45 amino acid monomeric dual agonist peptide that contains amino acid sequence motifs present within the blood glucose-lowering agent exendin-4 (Ex-4) and the appetite-suppressing agent PYY(3-36). In a new high-throughput FRET assay that provides real-time kinetic information concerning levels of cAMP in living cells, EP45 recapitulates the action of Ex-4 to stimulate cAMP production via the glucagon-like peptide-1 receptor (GLP-1R), while also recapitulating the action of PYY(3-36) to inhibit cAMP production via the neuropeptide Y2 receptor (NPY2R)...
February 28, 2018: Scientific Reports
Liina Remmel, Vallo Tillmann, Priit Purge, Evelin Lätt, Jaak Jürimäe
The aim of this study was to investigate the differences in associations of serum acylated and des-acylated ghrelin, peptide YY (PYY) and leptin levels with physical activity (PA) and cardiorespiratory fitness (CReF) in adolescent boys (mean age of 14.0 years) with overweight (OWB; n=55) and with normal weight (NWB; n=154). METHODS: Total PA was measured by 7-day accelerometry (counts/min) and CReF by peak oxygen consumption (VO2 peak/kg). RESULTS: No differences were found in serum PYY, acylated ghrelin or des-acyl ghrelin levels, whereas mean leptin (11...
December 2017: Biology of Sport
Iain R Tough, Sarah Forbes, Herbert Herzog, Robert M Jones, Thue W Schwartz, Helen M Cox
The lipid sensor GPR119 is highly expressed by enteroendocrine L-cells and pancreatic β-cells that release the hormones, PYY and GLP-1, and insulin, respectively. Endogenous oleoylethanolamide (OEA) and the dietary metabolite, 2-monoacylglycerol (2-OG) can each activate GPR119. Here we compared mucosal responses to selective, synthetic GPR119 agonists (AR440006, AR231453) and the lipids, OEA, 2-OG and N-oleoyldopamine (OLDA) monitoring epithelial ion transport as a read-out for L-cell activity in native mouse and human gastrointestinal (GI) mucosae...
February 19, 2018: Endocrinology
Patricio Atanes, Inmaculada Ruz-Maldonado, Ross Hawkes, Bo Liu, Min Zhao, Guo Cai Huang, Israa Mohammed Al-Amily, Albert Salehi, Stefan Amisten, Shanta J Persaud
INTRODUCTION: Islets synthesise and secrete numerous peptides, some of which are known to be important regulators of islet function and glucose homeostasis. In this study, we quantified mRNAs encoding all peptide ligands of islet G protein-coupled receptors (GPCRs) in isolated human and mouse islets and carried out in vitro islet hormone secretion studies to provide functional confirmation for the species-specific role of peptide YY (PYY) in mouse islets. MATERIALS AND METHODS: GPCR peptide ligand mRNAs in human and mouse islets were quantified by quantitative real-time PCR relative to the reference genes ACTB, GAPDH, PPIA, TBP and TFRC...
February 17, 2018: Cellular and Molecular Life Sciences: CMLS
Linn Bøhler, Sílvia Ribeiro Coutinho, Jens F Rehfeld, Linda Morgan, Catia Martins
Active, as opposed to inactive, individuals are able to adjust their energy intake after preloads of different energy content. The mechanisms responsible for this remain unknown. This study examined differences in plasma concentration of appetite-related hormones in response to breakfasts of different energy content, between active and inactive men. 16 healthy non-obese (BMI 18.5-27 kg/m 2 ) adult males (9 active, 7 inactive), participated in the study. Participants were given a high- (HE, 570 kcal) or a low-energy (LE, 205 kcal) breakfast in random order...
February 12, 2018: International Journal of Sport Nutrition and Exercise Metabolism
Chihiro Yamada, Sachiko Mogami, Hitomi Kanno, Tomohisa Hattori
Apathy is observed across several neurological and psychiatric conditions; however, its pathogenesis remains unclear. We clarified the involvement of brain-gut signaling in the disruption of goal-directed behavior. Male C57BL/6J mice were exposed to water immersion (WI) stress for 3 days. Food intake and nesting behavior were measured as indexes of motivation. Repeated WI caused decrease in food intake and nesting behavior. Plasma levels of peptide YY (PYY), IL-6, and ratio of dopamine metabolites in the striatum were significantly elevated after WI...
February 10, 2018: Molecular Neurobiology
Giuseppina Costabile, Ettore Griffo, Paola Cipriano, Claudia Vetrani, Marilena Vitale, Gianfranco Mamone, Angela A Rivellese, Gabriele Riccardi, Rosalba Giacco
Dietary fiber and whole grain foods may contribute to the regulation of appetite; however, evidence has produced inconclusive findings. The objective was to evaluate the effects of an experimental wholemeal pasta on appetite ratings, plasma concentrations of gastrointestinal hormones involved in appetite control, and postprandial glucose/insulin responses in healthy adults. Fourteen healthy adults (7M/7F), mean age 30 ± 2 yrs (mean ± SEM), participated in a randomized, controlled, crossover trial...
February 7, 2018: Appetite
Fiona M Gribble, Claire L Meek, Frank Reimann
A new strategy under development for the treatment of type 2 diabetes and obesity is to mimic some of the effects of bariatric surgery by delivering food-related stimuli to the distal gastrointestinal tract where they should enhance the release of gut hormones such as glucagon-like peptide-1 (GLP-1) and peptideYY (PYY). Methods include inhibition of food digestion and absorption in the upper GI tract, or oral delivery of stimuli in capsules or pelleted form to protect them against gastric degradation. A variety of agents have been tested in humans using capsules, microcapsules or pellets, delivering nutrients, bile acids, fatty acids and bitter compounds...
February 2018: Peptides
Ryan A Lafferty, Peter R Flatt, Nigel Irwin
The vast majority of research to date on the gut hormone Peptide YY (PYY) has focused on appetite suppression and body weight regulation effects. These biological actions are believed to occur through interaction of PYY with hypothalamic Y2 receptors. However, more recent studies have added additional knowledge to understanding of the physiological, and potential therapeutic, roles of PYY beyond obesity alone. Thus, PYY has now been shown to impart improvements in pancreatic beta-cell survival and function, with obvious benefits for diabetes...
February 2018: Peptides
S Saral, M Alkanat, A Sumer, S Canpolat
In this study, we aimed to explain the role of apelin-13 on body weight, food and water intake with serum leptin, ghrelin, neuropeptid Y (NPY) and peptid YY (PYY) levels in male rat. Thirty-two Sprague-Dawley male rats were used for the study. The rats were injected SP (0.9 %) intraperitoneally (i.p) in the control group and 30 (AP30), 100 (AP100) and 300 (AP300) µg/kg apelin-13 in the study groups, respectively, 10 min before the transition to dark period, for 10 days. During the experimental period, with light and dark periods of food and water intake, body weights were recorded in rats...
2018: Bratislavské Lekárske Listy
Ehsan Parvaresh Rizi, Tze Ping Loh, Sonia Baig, Vanna Chhay, Shiqi Huang, Jonathan Caleb Quek, E Shyong Tai, Sue-Anne Toh, Chin Meng Khoo
It is known that the macronutrient content of a meal has different impacts on the postprandial satiety and appetite hormonal responses. Whether obesity interacts with such nutrient-dependent responses is not well characterized. We examined the postprandial appetite and satiety hormonal responses after a high-protein (HP), high-carbohydrate (HC), or high-fat (HF) mixed meal. This was a randomized cross-over study of 9 lean insulin-sensitive (mean±SEM HOMA-IR 0.83±0.10) and 9 obese insulin-resistant (HOMA-IR 4...
2018: PloS One
Jiawei Wang, Chunfu Qin, Ting He, Kai Qiu, Wenjuan Sun, Xin Zhang, Ning Jiao, Weiyun Zhu, Jingdong Yin
Background: Pork produced by outdoor-reared pigs raised mostly on alfalfa pastures attracts increasing population of consumer from most of the world. In China, pigs were raised with alfalfa-containing diets to seek for good quality pork. However, the influence of dietary alfalfa involving high level of insoluble dietary fiber (IDF) on pig intestinal luminal microbiota composition remains unclear. The objective of this study was to investigate the effects of alfalfa on luminal microbiota and short chain fatty acids (SCFA) production, and gene expressions involved in SCFA sensing, transporting and absorbing in pig caecal mucosa...
2018: Journal of Animal Science and Biotechnology
Bo Xu, Silvana Vasile, Soren Ostergaard, Johan F Paulsson, Jasna Pruner, Johan Aqvist, Birgitte S Wulff, Hugo Gutierrez-de-Teran, Dan Larhammar
Understanding the agonist-receptor interactions in the neuropeptide Y (NPY)/peptide YY (PYY) signaling system is fundamental for the design of novel modulators of appetite regulation. We report here a binding model for the native peptide agonist PYY to the human Y2 receptor based on computational and in vitro pharmacological analyses. The Molecular Dynamics (MD) simulations yielded a conserved binding orientation for the full PYY and five analogues truncated at the amino terminus, which were pharmacologically characterized...
January 24, 2018: Molecular Pharmacology
Silvia R Coutinho, Jens F Rehfeld, Jens J Holst, Bård Kulseng, Catia Martins
The impact of lifestyle-induced weight loss (WL) on appetite in patients with obesity remains controversial. This study aimed was to assess the short- and long-term impact of WL achieved by diet and exercise, on appetite in patients with obesity. Thirty-five (22 females) adults with severe obesity (BMI: 42.5{plus minus}5.0 kg/m2) underwent a 2-year WL program focusing on diet and exercise. Body weight (BW), cardiovascular fitness (VO2max), appetite feelings and plasma concentrations of insulin, active ghrelin (AG), glucagon-like peptide 1 (GLP-1), peptide YY (PYY) and cholecystokinin (CCK), in the fasting and postprandial states, were measured at baseline (B), week 4 (W4), 1 and 2-years (and average values for all fasting and postprandial time points computed)...
January 23, 2018: American Journal of Physiology. Endocrinology and Metabolism
Caroline Giezenaar, Natalie D Luscombe-Marsh, Amy T Hutchison, Scott Standfield, Christine Feinle-Bisset, Michael Horowitz, Ian Chapman, Stijn Soenen
Protein-rich supplements are used widely for the prevention and management of malnutrition in older people. We have reported that healthy older, compared to younger, adults have less suppression of energy intake by whey-protein-effects on appetite-related hormones are unknown. The objective was to determine the effects of intraduodenally administered whey-protein on glucose, gut hormone, and amino acid concentrations, and their relation to subsequent ad libitum energy intake at a buffet meal, in healthy older and younger men...
January 12, 2018: Nutrients
P Larraufie, C Martin-Gallausiaux, N Lapaque, J Dore, F M Gribble, F Reimann, H M Blottiere
Peptide-YY (PYY) and Glucagon-Like Peptide-1 (GLP-1) play important roles in the regulation of food intake and insulin secretion, and are of translational interest in the field of obesity and diabetes. PYY production is highest in enteroendocrine cells located in the distal intestine, mirroring the sites where high concentrations of short chain fatty acids (SCFAs) are produced by gut microbiota. We show here that propionate and butyrate strongly increased expression of PYY but not GCG in human cell line and intestinal primary culture models...
January 8, 2018: Scientific Reports
Ayumu Niida, Yoko Kanematsu-Yamaki, Tomoko Asakawa, Yoshimasa Ishimura, Hisashi Fujita, Kouta Matsumiya, Naoki Nishizawa, Yusuke Adachi, Taisuke Mochida, Kazue Tsuchimori, Mariko Yoneyama-Hirozane, Junichi Sakamoto, Hideki Hirabayashi, Hideo Fukui, Shiro Takekawa, Taiji Asami
Neuropeptide Y2 receptor (Y2R) agonism is an important anorectic signal and a target of antiobesity drug discovery. Recently, we synthesized a short-length Y2R agonist, PYY-1119 (4-imidazolecarbonyl-[d-Hyp24,Iva25,Pya(4)26,Cha27,36,γMeLeu28,Lys30,Aib31]PYY(23-36), 1) as an antiobesity drug candidate. Compound 1 induced marked body weight loss in diet-induced obese (DIO) mice; however, 1 also induced severe vomiting in dogs at a lower dose than the minimum effective dose administered to DIO mice. The rapid absorption of 1 after subcutaneous administration caused the severe vomiting...
December 8, 2017: Bioorganic & Medicinal Chemistry
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