leptin and tyrosyltyrosine

The vagal link between the gastrointestinal tract and the central nervous system (CNS) has numerous vital functions for maintaining homeostasis. The regulation of energy balance is one which is attracting more and more attention due to the potential for exploiting peripheral hormonal targets as treatments for conditions such as obesity. While physiologically, this system is well tuned and demonstrated to be effective in the regulation of both local function and promoting/terminating food intake the neural connection represents a susceptible pathway for disruption in various disease states. Numerous studies have revealed that obesity in particularly is associated with an array of modifications in vagal afferent function from changes in expression of signaling molecules to altered activation mechanics. In general, these changes in vagal afferent function in obesity further promote food intake instead of the more desirable reduction in food intake. It is essential to gain a comprehensive understanding of the mechanisms responsible for these detrimental effects before we can establish more effective pharmacotherapies or lifestyle strategies for the treatment of obesity and the maintenance of weight loss.

Topics: Animals; Cholecystokinin; Dipeptides; Eating; Gastrointestinal Tract; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Microbiota; Neuronal Plasticity; Obesity; Satiation; Signal Transduction; Vagus Nerve

Apolipoprotein A-IV (apo A-IV) is secreted by the intestine associated with chylomicron. Intestinal apo A-IV synthesis is stimulated by fat absorption, which is probably mediated by chylomicron formation. The stimulation of apo A-IV synthesis in the jejunum and ileum is attenuated by intravenous leptin infusion. Intestinal apo A-IV synthesis is also stimulated by a factor from the ileum, probably peptide tyrosine-tyrosine (PYY), which has been demonstrated to affect satiety. Apo A-IV has been proposed to physiologically control food intake, a function not shared by apo A-I, and this inhibitory effect is centrally mediated. Recently, apo A-IV was demonstrated in the hypothalamus. The hypothalamic apo A-IV level was reduced by food deprivation and restored by lipid feeding. Intracerebroventricular administration of apo A-IV antiserum increased feeding and decreased the hypothalamic apo A-IV mRNA level, implying that feeding is normally limited by endogenous apo A-IV. Central administration of neuropeptide Y (NPY) significantly increased hypothalamic apo A-IV mRNA levels in a dose-dependent manner. The stimulation of intestinal synthesis and secretion of apo A-IV by lipid absorption are rapid; thus, apo A-IV is capable of short-term regulation of food intake. Evidence also suggests apo A-IV's involvement in the long-term regulation of food intake and body weight. Chronic ingestion of high fat blunts the hypothalamic apo A-IV response to lipid feeding and may therefore explain why chronic intake of high fat predisposes animals and humans to obesity.

Topics: Adrenalectomy; Animals; Apolipoproteins A; Circadian Rhythm; Dipeptides; Dose-Response Relationship, Drug; Eating; Humans; Hypothalamus; Intestine, Small; Leptin; Lipid Metabolism; Neuropeptide Y; Obesity; Vagotomy

The effect of nonnutritive sweeteners on appetite is controversial. Some studies have found changes in certain appetite control hormones with sucralose intake that may be through interaction with sweet taste receptors located in the intestine.. The aim of this study was to evaluate whether sucralose consumption could produce changes in fasting plasma concentrations of appetite-regulating hormones, including glucagon-like peptide 1, ghrelin, peptide tyrosine tyrosine, and leptin, and secondarily in insulin resistance.. A 2-week parallel randomized clinical trial with an additional visit conducted 1 week after dosing termination.. Sixty healthy, normal-weight individuals, without habitual consumption of nonnutritive sweeteners were recruited from July 2015 to March 2017 in Mexico City.. Daily sucralose consumption at 15% of the acceptable daily intake by using commercial sachets added to food. The control group followed the same protocol without an intervention.. Fasting concentrations of appetite regulating hormones before and after the intervention. Fasting glucose and insulin concentrations were measured to assess insulin resistance as a secondary outcome.. Basal and final concentrations were compared using Wilcoxon matched-pairs test and Mann-Whitney U test for analysis between groups. Repeated measures analysis of variance was used to evaluate changes in the homeostasis model assessment of insulin resistance.. Sucralose was not associated with changes in any of the hormones measured. One week postintervention, an incremental change (P=0.04) in the homeostasis model assessment of insulin resistance was found in the intervention group.. Sucralose intake is not associated with changes in fasting concentrations of glucagon-like peptide 1, ghrelin, peptide tyrosine tyrosine, or leptin. An increase in the homeostasis model assessment of insulin resistance observed only at 1 week postdosing is of unknown clinical significance, if any.

Topics: Adult; Appetite; Blood Glucose; Diet; Dipeptides; Fasting; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Leptin; Male; Mexico; Sucrose

It remains unknown whether sustained daily feeding-fasting patterns modify the acute response to specific feedings on a given day.. We conducted a randomized controlled trial to establish if daily breakfast consumption or fasting until noon modifies the acute metabolic and appetitive responses to a fixed breakfast and ad libitum lunch.. With the use of a parallel group design, we randomly assigned 31 healthy, lean men and women (22-56 y) to 6 wk of either consuming ≥700 kcal of self-selected items before 1100 or fasting (0 kcal) until 1200 daily. Following 48 h of diet and physical activity standardization, we examined metabolic and appetite responses to a standardized breakfast and ad libitum lunch before and after the intervention. Data were analyzed using 3- and 2-way ANCOVA.. Systemic concentrations of energy balance regulatory hormones total and acylated ghrelin, leptin, and peptide tyrosine-tyrosine) responded similarly to breakfast and lunch before and after 6 wk of either morning fasting or regular breakfast, with the exception of a tendency for increased glucagon-like peptide-1 concentrations from baseline to follow-up in the Breakfast Group compared with a decrease over that period in the Fasting Group [P = 0.06, partial eta squared value (ƞ2) = 0.16]. Subjective appetite sensations also did not differ over the course of the day, and ad libitum energy intake at lunch was not systematically affected by either intervention, decreasing by 27 kcal (95% CI: -203, 149 kcal) with fasting and by 77 kcal (95% CI: -210, 56 kcal) with breakfast. Similarly, glycemic, insulinemic, lipemic, and thermogenic responses to breakfast and lunch were very stable at baseline and follow-up and, thus, did not differ between treatment groups.. Our results indicate that a sustained period of either extended morning fasting or eating a daily breakfast has minimal effect upon acute metabolic and appetite responses in lean adults. This trial was registered at www.isrctn.org as ISRCTN31521726.

Topics: Adult; Appetite; Blood Glucose; Body Mass Index; Breakfast; Cross-Over Studies; Dipeptides; Energy Metabolism; Exercise; Fasting; Female; Follow-Up Studies; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Leptin; Lunch; Male; Metabolism; Middle Aged; Postprandial Period; Young Adult

Breakfast omission is positively associated with obesity and increased risk of disease. However, little is known about the acute effects of extended morning fasting upon subsequent energy intake and associated metabolic/regulatory factors in obese adults.. In a randomised cross-over design, 24 obese men (n=8) and women (n=16) extended their overnight fast by omitting breakfast consumption or ingesting a typical carbohydrate-rich breakfast of 2183±393 kJ (521±94 kcal), before an ad libitum pasta lunch 3 h later. Blood samples were obtained throughout the day until 3 h post lunch and analysed for hormones implicated in appetite regulation, along with metabolic outcomes and subjective appetite measures.. Lunch intake was unaffected by extended morning fasting (difference=218 kJ, 95% confidence interval -54 kJ, 490 kJ; P=0.1) resulting in lower total intake in the fasting trial (difference=-1964 kJ, 95% confidence interval -1645 kJ, -2281 kJ; P<0.01). Systemic concentrations of peptide tyrosine-tyrosine and leptin were lower during the afternoon following morning fasting (P⩽0.06). Plasma-acylated ghrelin concentrations were also lower following the ad libitum lunch in the fasting trial (P<0.05) but this effect was not apparent for total ghrelin (P⩾0.1). Serum insulin concentrations were greater throughout the afternoon in the fasting trial (P=0.05), with plasma glucose also greater 1 h after lunch (P<0.01). Extended morning fasting did not result in greater appetite ratings after lunch, with some tendency for lower appetite 3 h post lunch (P=0.09).. We demonstrate for the first time that, in obese adults, extended morning fasting does not cause compensatory intake during an ad libitum lunch nor does it increase appetite during the afternoon. Morning fasting reduced satiety hormone responses to a subsequent lunch meal but counterintuitively also reduced concentrations of the appetite-stimulating hormone-acylated ghrelin during the afternoon relative to lunch consumed after breakfast.

Topics: Adult; Appetite Regulation; Blood Glucose; Breakfast; Cross-Over Studies; Dietary Carbohydrates; Dipeptides; Energy Intake; England; Fasting; Female; Ghrelin; Humans; Leptin; Lunch; Male; Middle Aged; Obesity; Postprandial Period; Reproducibility of Results; Satiety Response; Time Factors

An acute bout of high-intensity intermittent exercise suppresses ad libitum energy intake at the postexercise meal. The present study examined the effects of 12 wk of high-intensity intermittent exercise training (HIIT) compared with moderate-intensity continuous exercise training (MICT) on appetite regulation.. Thirty overweight inactive men (body mass index, 27.2 ± 1.3 kg·m(-2); V˙O2peak, 35.3 ± 5.3 mL·kg(-1)·min(-1) were randomized to either HIIT or MICT (involving 12 wk of training, three sessions per week) or a control group (CON) (n = 10 per group). Ad libitum energy intake from a laboratory test meal was assessed after both a low-energy (847 kJ) and a high-energy preload (2438 kJ) before and after the intervention. Perceived appetite and appetite-related blood variables were also measured.. There was no significant effect of the intervention period on energy intake at the test meal after the two different preloads (P ≥ 0.05). However, the 95% confidence interval indicated a clinically meaningful decrease in energy intake after the high-energy preload compared with the low-energy preload in response to HIIT (516 ± 395 kJ decrease), but not for MICT or CON, suggesting improved appetite regulation. This was not associated with alterations in the perception of appetite or the circulating concentration of a number of appetite-related peptides or metabolites, although insulin sensitivity was enhanced with HIIT only (P = 0.003).. HIIT seems to benefit appetite regulation in overweight men. The mechanisms for this remain to be elucidated.

Topics: Appetite Regulation; Blood Glucose; Dipeptides; Energy Intake; Exercise; Exercise Therapy; Ghrelin; Humans; Insulin; Leptin; Male; Overweight; Pancreatic Polypeptide; Physical Education and Training

Breakfast omission is associated with obesity and CVD/diabetes, but the acute effects of extended morning fasting upon subsequent energy intake and metabolic/hormonal responses have received less attention. In a randomised cross-over design, thirty-five lean men (n 14) and women (n 21) extended their overnight fast or ingested a typical carbohydrate-rich breakfast in quantities relative to RMR (i.e. 1963 (sd 238) kJ), before an ad libitum lunch 3 h later. Blood samples were obtained hourly throughout the day until 3 h post-lunch, with subjective appetite measures assessed. Lunch intake was greater following extended fasting (640 (sd 1042) kJ, P< 0.01) but incompletely compensated for the omitted breakfast, with total intake lower than the breakfast trial (3887 (sd 1326) v. 5213 (sd 1590) kJ, P< 0.001). Systemic concentrations of peptide tyrosine-tyrosine and leptin were greater during the afternoon following breakfast (both P< 0.05) but neither acylated/total ghrelin concentrations were suppressed by the ad libitum lunch in the breakfast trial, remaining greater than the morning fasting trial throughout the afternoon (all P< 0.05). Insulin concentrations were greater during the afternoon in the morning fasting trial (all P< 0.01). There were no differences between trials in subjective appetite during the afternoon. In conclusion, morning fasting caused incomplete energy compensation at an ad libitum lunch. Breakfast increased some anorectic hormones during the afternoon but paradoxically abolished ghrelin suppression by the second meal. Extending morning fasting until lunch altered subsequent metabolic and hormonal responses but without greater appetite during the afternoon. The present study clarifies the impact of acute breakfast omission and adds novel insights into second-meal metabolism.

Topics: Adult; Appetite; Blood Glucose; Breakfast; Cross-Over Studies; Dietary Carbohydrates; Dipeptides; Energy Intake; Fasting; Fatty Acids, Nonesterified; Female; Ghrelin; Glucagon-Like Peptide 1; Glycemic Index; Humans; Insulin; Leptin; Lunch; Male; Meals; Middle Aged

What is the central question of this study? What are the interactions between sleep and appetite following early evening high-intensity interval exercise (HIIE)? What is the main finding and its importance? HIIE can be performed in the early evening without subsequent sleep disruptions and may favourably alter appetite-related hormone concentrations. Nonetheless, perceived appetite and energy intake do not change with acute HIIE regardless of time of day.. Despite exercise benefits for sleep and appetite, due to increased time restraints, many adults remain inactive. Methods to improve exercise compliance include preferential time-of-day or engaging in short-duration, high-intensity interval exercise (HIIE). Hence, this study aimed to compare effects of HIIE time-of-day on sleep and appetite. Eleven inactive men undertook sleep monitoring to determine baseline (BASE) sleep stages and exclude sleep disorders. On separate days, participants completed 30 min HIIE (60 s work at 100%

Topics: Adult; Appetite Regulation; Dipeptides; Energy Intake; Ghrelin; High-Intensity Interval Training; Humans; Leptin; Male; Middle Aged; Overweight; Oxygen Consumption; Sleep

Dietary fat supplementation during the periparturient period is one strategy to increase energy intake and attenuate the degree of negative energy balance during early lactation; however, little is known of the underlying hormonal and metabolic adaptations. We evaluated the effects of prepartum fat supplementation on energy-balance parameters and plasma concentrations of glucagon-like peptide-1, peptide tyrosine-tyrosine (PYY), adropin, insulin, leptin, glucose, nonesterified fatty acid, and β-hydroxybutyric acid in dairy cows. Twenty-four pregnant dairy cows were randomized to diets containing either rolled canola or sunflower seed at 8% of dry matter, or no oilseed supplementation, during the last 5 wk of gestation and then assigned to a common lactation diet postpartum. Blood samples were collected at -2, +2, and +14 h relative to feeding, at 2 wk after the initiation of the diets, and at 2 wk postpartum. Dietary canola and sunflower supplementation alone did not affect energy balance, body weight, and plasma concentrations of glucagon-like peptide-1, PYY, adropin, insulin, leptin, nonesterified fatty acid, and β-hydroxybutyric acid; however, canola decreased and sunflower tended to decrease dry matter intake. We also observed that the physiological stage had a significant, but divergent, effect on circulating hormones and metabolite concentrations. Plasma glucagon-like peptide-1, PYY, adropin, nonesterified fatty acid, and β-hydroxybutyric acid concentrations were greater postpartum than prepartum, whereas glucose, insulin, leptin, body weight, and energy balance were greater prepartum than postpartum. Furthermore, the interaction of treatment and stage was significant for leptin and adropin, and tended toward significance for PYY and insulin; only insulin exhibited an apparent postprandial increase. Postpartum PYY concentrations exhibited a strong negative correlation with body weight, suggesting that PYY may be associated with body weight regulation during the transition period. These novel findings demonstrate that the transition from pregnancy to lactation is a stronger determinant of circulating gut hormone concentrations than dietary lipid in transition dairy cows.

Topics: 3-Hydroxybutyric Acid; Animals; Blood Proteins; Body Weight; Cattle; Diet; Dietary Fats; Dietary Supplements; Dipeptides; Energy Intake; Energy Metabolism; Fatty Acids, Nonesterified; Female; Glucagon-Like Peptide 1; Hormones; Insulin; Lactation; Leptin; Peptide YY; Postpartum Period; Pregnancy; Random Allocation

Understanding the etiologic mechanisms underlying impaired glucose tolerance in obstructive sleep apnea (OSA) would assist development of therapies against this comorbidity. We hypothesized that in patients with OSA impaired glucose tolerance (IGT) would be associated with elevated levels of hormones associated with appetite regulation (leptin, ghrelin, neuropeptide Y [NPY] and peptide tyrosine-tyrosine [PYY]).. We studied 68 OSA patients (mean AHI 22 events/h) and 37 age and weight matched healthy controls recruited by advertisement. All participants received a standardized evening meal, attended polysomnography and an oral glucose tolerance test (OGTT) on waking. Hormones were measured in blood taken before sleep (22:30) and at the start of the OGTT.. Impaired glucose tolerance was present in 54% of patients and 32% of controls (p = 0.05). The only differences between groups was that leptin was significantly higher at 22:30 in OSA patients compared to controls (9.6 ng/L vs 7.9 ng/L, p = 0.05). OSA patients had marginally elevated plasma NPY levels at 22:30 (56.6 [52, 67] pmol/L vs 51.1[47.3, 61] pmol/L; p = 0.04). No differences in ghrelin, PYY or NPY were observed between patients with IGT and those without. However OSA patients with IGT had significantly higher value of leptin at both 22:30 (10.9 [7.7, 15.9] ng/mL vs 7.4 [5.6, 12.3] ng/mL, p = 0.02) and 07:00 (11.6 [7.6, 16.2] ng/mL vs 6.9 [5.4, 12.6] ng/mL, p = 0.024) than those without. In multivariate analysis the only major association of leptin was body mass index.. Clinically significant abnormalities of appetite regulating hormones are not present in OSA. Appetite regulating hormones did not differ in OSA patients with and without impaired glucose tolerance.

Topics: Blood Glucose; Dipeptides; Ghrelin; Glucose Intolerance; Glucose Tolerance Test; Humans; Leptin; Middle Aged; Neuropeptide Y; Risk Factors; Sleep Apnea, Obstructive

Type 2 diabetes is characterized by hyperglycaemia, delayed gastric emptying and a blunted response of gut hormones during feeding that may modulate satiety. We hypothesized that it is associated with more hunger when treated by medication.. We studied nine type 2 diabetic men (A1C: 6.7+/-0.3%, waist circumference: 104+/-4 cm) after an overnight fast, during 5 h in response to a 2.88 MJ breakfast, twice, in a crossover design, with or without antihyperglycaemic agents. Satiety ratings, thermic effect of meal, gastric emptying, plasma concentrations of gut peptides, leptin, insulin and substrates and intake from a subsequent buffet were determined.. With medication, fasting and postprandial plasma glucose levels were lower but area under the curve (AUC) did not vary vs. without medication. Gastric emptying was shortened, branched chain amino acids (BCAA) AUC and thermic effect were lower, and postprandial glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY3-36) were maintained at higher levels beyond 4 h. Correlations were significant between duration of diabetes and fasting ghrelin (r=0.779, p=0.013) and peak insulin (r=-0.769, p=0.016), 5-h postmeal ghrelin and peak glucose (r=0.822, p=0.007), 5-h glucose and GLP-1 (r=-0.788, p=0.012), and 5-h hunger scores and energy intake at buffet (r=0.828, p=0.006). Without medication, fullness scores correlated with BCAA levels. Visual analogue scale scores, ghrelin and leptin levels did not differ between studies.. The decrease in factors associated with postprandial satiety with treatment is counterbalanced by higher GLP-1 and PYY3-36. Medication may normalize the link between perception of hunger and subsequent food intake.

Topics: Aged; Amino Acids; Area Under Curve; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Dipeptides; Fasting; Gastric Emptying; Glucagon-Like Peptide 1; Glyburide; Humans; Hunger; Hypoglycemic Agents; Insulin; Leptin; Male; Metformin; Middle Aged; Postprandial Period; Satiation; Thiazolidinediones