Plasma Peptide Tyrosine-tyrosine Research Articles

RISE IN PLASMA BILE ACIDS FOLLOWING HYPOABSORPTIVE BARIATRIC SURGERIES PREDICT BENEFICIAL METABOLIC AND HOMEOSTATIC OUTCOMES IN MALE RATS.

The effects of three hypoabsorptive bariatric surgeries, Roux-en-Y gastric bypass (RYGB), biliopancreatic diversion with duodenal switch (BPD-DS) and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S), on bile acids (BAs) were assessed including the changes in BA plasma levels associated with the metabolic and homeostatic effects of the surgeries. Male Wistar rats, etheir fed high- (HF) or a low-fat (LF) diets, were divided into seven groups: RYGB HF, BPD-DS HF, SADI-S HF, sleeve-gastrectomy (SG) HF, sham-operation (SHAM) HF, SHAM LF and SHAM HF-pair-weighed to BPD-DS (SHAM HF-PW). The rats were treated 56 days. The results demonstrate the ability of RYGB, BPD-DS and SADI-S to raise plasma levels of BAs, whose elevations, most notably those of the secondary BAs (deoxycholic acid, ursodooxycholic acid and lithocholic acid) associated negatively with body weight gain, fat gain and fasting insulin levels and positively with plasma peptide tyrosine-tyrosine (PYY). Plasma BAs also correlated positively with the fecal levels of Clostridium, Sutterella and Enterobacteriaceae and negatively with Clostridiales_f_g_2, Christensenellaceae, Ruminococcaceae_g_2, Oscillibacter and Oscillospira. Additionally, they associated positively with the short-chain fatty acid (SCFA) levels of propionate, butyrate, isobutyrate, valerate and isovalerate. Altogether, the present study emphasizes the ability of RYGB, BPD-DS and SADI-S to induce circulating BA elevations that predict the beneficial consequences of those hypoabsorptive bariatric surgeries on energy and glucose homeostasis and circulating levels of PYY. The present results also reveal close associations between plasma BAs and SCFAs, whose variations following hypoabsorptive surgeries are also linked to significant fat losses and metabolic health improvements.

Involvement of the vagus nerve in the anorectic effect of monoacylglycerol acyltransferase 2 inhibition in mice.

Many of the drugs used for obesity treatment have adverse effects on the central nervous system. Therefore, novel treatments, such as peripherally acting drugs, are needed. Monoacylglycerol acyltransferase 2 (MGAT2), highly expressed in the small intestine, catalyzes the first step of triacylglycerol re-synthesis. MGAT2 inhibition suppresses food intake in high-fat diet (HFD)-fed mice, but the mechanisms remain unclear. Here, the involvement of the vagus nerve in MGAT2 inhibition-induced feeding suppression was investigated. Fasted mice were administered an MGAT2 inhibitor. Food intake was measured after HFD re-feeding, and the effect of capsaicin pretreatment on changes in food intake was evaluated. The number of c-fos-positive cells in the nucleus tractus solitarius and levels of appetite regulators were determined after HFD re-feeding or lipid gavage. The anorectic effect of the MGAT2 inhibitor was abolished when vagus nerve function was interrupted by capsaicin. MGAT2 inhibition increased the number of c-fos-positive cells in the nucleus tractus solitarius and elevated intestinal oleoylethanolamide, plasma peptide tyrosine-tyrosine and plasma glucagon-like peptide-1 levels. MGAT2 inhibition suppresses feeding behavior via peripheral vagus nerve signaling and may serve as a novel anti-obesity strategy with a low risk of unexpected central nervous system-related adverse effects.

Gut Microbiota Mediates Lactobacillus rhamnosus GG Alleviation of Deoxynivalenol-Induced Anorexia.

Deoxynivalenol (DON) is a widespread mycotoxin and causes anorexia and emesis in humans and animals; Lactobacillus rhamnosus GG (LGG), a well-characterized probiotic, can improve intestinal barrier function and modulate immune response. Currently, it is unclear whether LGG has a beneficial effect on DON-induced anorexia. In the present study, mice were treated with DON, LGG, or both by gavage for 28 days to evaluate the effects of LGG on DON-induced anorexia. Antibiotic treatment and fecal microbiota transplant (FMT) experiment were also conducted to investigate the link between DON, LGG, and gut microbiota. LGG significantly increased the villus height and reduced the crypt depth in jejunum and ileum, enhanced the tight junction proteins expression in the intestine, and regulated the TLR4/NF-κB signaling pathway, consequently attenuating the intestinal inflammation caused by DON. In addition, LGG increased the relative abundance of Lactobacillus and butyric acid production of cecal contents; remodeled phenylalanine metabolism and tryptophan metabolism; reduced plasma peptide tyrosine tyrosine (PYY), 5-hydroxytryptamine (5-HT), and glucagon-like peptide-1 (GLP-1) concentrations; and promoted hypothalamic NPY and AgPR gene expression, which will further promote food intake and reduce weight loss, ultimately alleviating DON-induced anorexia in mice. Interestingly, antibiotic treatment diminished the intestinal toxicity of DON. The FMT experiment showed that DON-originated microbiota promotes intestinal inflammation and anorexia, while LGG + DON-originated microbiota has no adverse effects on mice. Both antibiotic treatment and FMT experiment have proved that gut microbiota was the primary vector for DON to exert its toxic effects and an essential mediator of LGG protection. In summary, our findings demonstrate that gut microbiota plays essential roles in DON-induced anorexia, and LGG can reduce the adverse effects caused by DON through its structure and regulate the gut microbiota, which may lay the important scientific foundation for future applications of LGG in food and feed products.

Gastrointestinal hormone secretion in women with polycystic ovary syndrome: an observational study.

Is the secretion of gastrointestinal hormones impaired in patients with polycystic ovary syndrome (PCOS)? Gastrointestinal hormone levels were abnormal in patients with PCOS. The hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine-tyrosine (PYY) are both involved in signaling satiety. Secretion of GLP-1 and PYY in response to nutrients in the small intestine plays an important role in energy metabolism. Most PCOS patients are overweight or obese, which suggests dysregulation of appetite. In order to evaluate levels of gastrointestinal hormones in PCOS, a cohort study was undertaken, involving 30 PCOS patients and 29 BMI-matched healthy women recruited from Shanghai Renji Hospital between 1 March 2013 and 30 May 2014. After an overnight fast, all participants underwent an oral glucose tolerance test. Blood was sampled frequently for measurement of blood glucose and plasma insulin, total GLP-1 and PYY concentrations. Fasting and postprandial insulin levels were significantly higher in patients with PCOS compared with the healthy controls (P < 0.05). Fasting and postprandial GLP-1 (t = 0 and 30 min; mean ± SEM) were also higher in PCOS group (17.5 ± 1.07 pM versus 14.1 ± 1.16 pM, P < 0.05; 29.7 ± 2.39 pM versus 22.8 ± 2.09 pM, P < 0.05). However, there were no differences in plasma PYY between patients with PCOS and healthy controls either fasting or postprandially. PYY levels were lower in obese PCOS patients than in lean PCOS patients (P < 0.05). The study involved a small number of subjects with PCOS, and examined hormone responses to oral glucose rather than a physiological meal. Deficient secretion of GLP-1 and PYY does not contribute to excessive food intake in the pathophysiology of PCOS.

The Role of Viscosity and Fermentability of Dietary Fibers on Satiety- and Adiposity-Related Hormones in Rats

Dietary fiber may contribute to satiety. This study examined the effect of two dietary fiber characteristics, small intestinal contents viscosity and large intestinal fermentability, on satiety-and adiposity-related hormones in rats. Diets contained fiber sources that were non-viscous, somewhat viscous, or highly viscous, and either highly fermentable or non-fermentable, in a 2 × 3 factorial design. In the fed state (2 h postprandial), rats fed non-fermentable fibers had significantly greater plasma GLP-1 concentration than fermentable fibers. In the fasted state, among non-fermentable fibers, viscosity had no effect on GLP-1 concentration. However, among fermentable fibers, greater viscosity reduced GLP-1 concentration. Plasma peptide tyrosine tyrosine (PYY) concentrations in the fasted state were not influenced by the fermentability of the fiber overall, however animals consuming a fructooligosaccharide greater PYY concentration. In both the fed and fasted states, rats fed non-fermentable fibers had a significantly lower plasma ghrelin concentration than rats fed fermentable fibers. In the fasted state, rats fed non-fermentable fibers had a significantly lower plasma leptin concentration than rats fed fermentable fibers. Thus, fermentability and viscosity of dietary fiber interacted in complex ways to influence satiety- and adiposity-related plasma hormone concentrations. However, the results suggest that highly viscous, non-fermentable fibers may limit weight gain and reduce adiposity and non-fermentable fibers, regardless of viscosity, may promote meal termination.

Possible Mechanisms of Circulating PYY-Induced Satiation in Male Rats

Peptide tyrosine-tyrosine (PYY) is implicated in eating control, but the site(s) and mechanism(s) of its action remain uncertain. We tested acute effects of intrameal hepatic portal vein (HPV) PYY(3-36) infusions on eating in adult, male rats and measured HPV and jugular vein (JV) plasma levels of PYY in response to a solid, mixed-nutrient meal. We also examined the effects of HPV PYY(3-36) infusions on JV plasma levels, flavor acceptance, and neuronal activation. Intrameal HPV PYY(3-36) infusions [1 and 3 nmol/kg body weight (BW)] selectively reduced (P < 0.05) ongoing meal size. HPV PYY levels increased (P < 0.05) during a chow (12.5 kcal) or an isocaloric high-fat meal. JV PYY levels were generally lower than HPV levels but also increased in response to the chow meal. HPV PYY(3-36) infusion (1 nmol/kg BW) caused a greater increase in JV PYY than a meal, but neither 1 nor 3 nmol/kg BW PYY(3-36) caused conditioned flavor avoidance. HPV PYY(3-36) (1 nmol/kg BW) increased the number of c-Fos-expressing cells in the nucleus tractus solitarii, the hypothalamic arcuate and paraventricular nuclei, the central area of the amygdala, and the nucleus accumbens but not in the area postrema and parabrachial nucleus. These data show that HPV infusions of PYY(3-36) inhibit eating in rats without causing avoidance, and they identify some brain areas that might be involved. Endogenous PYY may induce satiation by acting directly in the brain, but further studies should examine whether PYY(3-36) administrations that mimic the meal-induced increase in plasma PYY are sufficient to inhibit eating.

Hepatic portal vein (HPV) peptide tyrosine-tyrosine (PYY) and meal-taking in rats

Peripheral administration of PYY inhibits eating, but the site, mechanism, and physiological relevance of PYY's eating-inhibitory action are unclear. Here we equipped adult male rats (n = 8) kept on a medium-fat diet with HPV catheters and infused (0.2 ml/min) glucagon-like peptide-1 (GLP-1), PYY (1.0 nmol/kg BW, each) or vehicle (V) by remote control during the first spontaneous nocturnal meal. Either peptide reduced (p < 0.05) ongoing meal size (V: 4.1 ± 0.2, PYY: 2.4 ± 0.2, GLP-1: 1.6 ± 0.1 g; mean ± SEM). Subsequent meal sizes and cumulative food intake (2 h and beyond) were unaffected. In 10 other rats kept on chow intra-meal HPV PYY (1.0 and 3.0 nmol/kg BW) infusions also reduced (p < 0.05) meal size (V: 2.6 ± 0.2, 0.33 nmol: 2.5 ± 0.4, 1.0 nmol: 1.8 ± 0.2, 3 nmol: 1.8 ± 0.2 g). Intragastric nutrient infusions usually stimulate intestinal PYY release, but so far circulating PYY has not been measured in relation to real meals in rats. We did so and found that an isocaloric chow or high fat (HF) meal (12.5 kcal) given at dark onset after 3 h food deprivation increased (p < 0.05) HPV plasma PYY concentration from 70 ± 6 (0 min) to 104 ± 9 pg/ml (chow) and from 56 ± 9 (0 min) to 85 ± 9 pg/ml (HF) at 15 min after meal onset. Plasma PYY did not increase under control conditions without a meal. These findings show that HPV PYY increases during normal meals in rats and that experimentally induced prandial increases in HPV PYY can acutely inhibit eating. Further studies should examine whether PYY administrations that mimic the meal-induced increase are sufficient to inhibit eating.

Metformin increases fasting plasma peptide tyrosine tyrosine (PYY) in women with polycystic ovarian syndrome (PCOS)

The beneficial effects of metformin in patients with type 2 diabetes mellitus (T2DM) and polycystic ovarian syndrome (PCOS) are thought to be in part due to weight reduction. However, the mechanisms by which metformin causes weight loss are unclear. We sought to determine whether circulating levels of the anorectic gut hormone peptide tyrosine tyrosine (PYY) show any correlation with metformin-induced weight loss. We examined the acute effects of orally administrated metformin on fasting PYY levels in eight healthy normal-weight female subjects. Subsequently, we evaluated the effects of 6 months metformin treatment on fasting PYY levels and anthropometric measurements in 20 women with PCOS. In normal-weight females 10 days' metformin treatment increased fasting PYY levels (P < 0.01). Similarly, in PCOS subjects metformin treatment increased fasting PYY concentrations (P < 0.05). In both groups a marked variation in PYY increase in response to metformin was observed. Long-term metformin treatment was associated with improvements in weight (P < 0.05), BMI (P < 0.05), fasting glucose (P < 0.05) and menstrual frequency (P < 0.01). Interestingly, change in PYY levels were correlated with change in waist circumference (r = 0.55, P < 0.05). Acute and chronic oral metformin administration increase fasting PYY levels and may contribute to metformin's weight loss effect. Further studies are now required to clarify whether changes in circulating PYY levels in response to metformin treatment can be used to predict which patients will subsequently lose weight long-term and gain cycle restoration.