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The endocrine effects of bitter tastant administration in the gastrointestinal system: intragastric versus intraduodenal administration.
Verbeure, W, Deloose, E, Tóth, J, Rehfeld, JF, Van Oudenhove, L, Depoortere, I, Tack, J
American journal of physiology. Endocrinology and metabolism. 2021;(1):E1-E10
Abstract
Bitter tastants are recently introduced as potential hunger-suppressive compounds, the so-called "Bitter pill." However, the literature about bitter administration lacks consistency in methods and findings. We want to test whether hunger ratings and hormone plasma levels are affected by: 1) the site of administration: intragastrically (IG) or intraduodenally (ID), 2) the bitter tastant itself, quinine hydrochloride (QHCl) or denatonium benzoate (DB), and 3) the timing of infusion. Therefore, 14 healthy, female volunteers participated in a randomized, placebo-controlled six-visit crossover study. After an overnight fast, DB (1 µmol/kg), QHCl (10 µmol/kg), or placebo were given IG or ID via a nasogastric feeding tube. Blood samples were taken 10 min before administration and every 10 min after administration for a period of 2 h. Hunger was rated at the same time points on a visual analogue scale. ID bitter administration did not affect hunger sensations, motilin, or acyl-ghrelin release compared with its placebo infusion. IG QHCl infusion tended to suppress hunger increase, especially between 50 and 70 min after infusion, simultaneously with reduced motilin values. Here, acyl-ghrelin was not affected. IG DB did not affect hunger or motilin, however acyl-ghrelin levels were reduced 50-70 minutes after infusion. Plasma values of glucagon-like peptide 1 and cholecystokinin were too low to be properly detected or to have any physiological relevance. In conclusion, bitter tastants should be infused into the stomach to reduce hunger sensations and orexigenic gut peptides. QHCl has the best potential to reduce hunger sensations, and it should be infused 60 min before food intake.NEW & NOTEWORTHY Bitter tastants are a potential new weight-loss treatment. This is a noninvasive, easy approach, which should be received with considerable enthusiasm by the public. However, literature about bitter administration lacks consistency in methods and findings. We summarize how the compound should be given based on: the site of administration, the best bitter compound to use, and at what timing in respect to the meal. This paper is therefore a fundamental step to continue research toward the further development of the "bitter pill."
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Increase of plasma erythroferrone levels during high-altitude exposure: A sub-analysis of the TOP OF HOMe study.
Emrich, IE, Scheuer, A, Wagenpfeil, S, Ganz, T, Heine, GH
American journal of hematology. 2021;(5):E179-E181
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Effects of altitude and recombinant human erythropoietin on iron metabolism: a randomized controlled trial.
Breenfeldt Andersen, A, Bonne, TC, Bejder, J, Jung, G, Ganz, T, Nemeth, E, Olsen, NV, Huertas, JR, Nordsborg, NB
American journal of physiology. Regulatory, integrative and comparative physiology. 2021;(2):R152-R161
Abstract
Current markers of iron deficiency (ID), such as ferritin and hemoglobin, have shortcomings, and hepcidin and erythroferrone (ERFE) could be of clinical relevance in relation to early assessment of ID. Here, we evaluate whether exposure to altitude-induced hypoxia (2,320 m) alone, or in combination with recombinant human erythropoietin (rHuEPO) treatment, affects hepcidin and ERFE levels before alterations in routine ID biomarkers and stress erythropoiesis manifest. Two interventions were completed, each comprising a 4-wk baseline, a 4-wk intervention at either sea level or altitude, and a 4-wk follow-up. Participants (n = 39) were randomly assigned to 20 IU·kg body wt-1 rHuEPO or placebo injections every second day for 3 wk during the two intervention periods. Venous blood was collected weekly. Altitude increased ERFE (P ≤ 0.001) with no changes in hepcidin or routine iron biomarkers, making ERFE of clinical relevance as an early marker of moderate hypoxia. rHuEPO treatment at sea level induced a similar pattern of changes in ERFE (P < 0.05) and hepcidin levels (P < 0.05), demonstrating the impact of accelerated erythropoiesis and not of other hypoxia-induced mechanisms. Compared with altitude alone, concurrent rHuEPO treatment and altitude exposure induced additive changes in hepcidin (P < 0.05) and ERFE (P ≤ 0.001) parallel with increases in hematocrit (P < 0.001), demonstrating a relevant range of both hepcidin and ERFE. A poor but significant correlation between hepcidin and ERFE was found (R2 = 0.13, P < 0.001). The findings demonstrate that hepcidin and ERFE are more rapid biomarkers of changes in iron demands than routine iron markers. Finally, ERFE and hepcidin may be sensitive markers in an antidoping context.
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Erythroferrone as a sensitive biomarker to detect stimulation of erythropoiesis.
Ramirez Cuevas, K, Schobinger, C, Gottardo, E, Voss, SC, Kuuranne, T, Tissot, JD, Favrat, B, Townsend, N, Leuenberger, N
Drug testing and analysis. 2020;(2):261-267
Abstract
Erythroferrone (ERFE) is a glycoprotein hormone secreted by erythroblasts in response to erythropoietin stimulation. ERFE suppresses the hepatic synthesis of the master iron-regulatory hormone, hepcidin. The impact of erythropoiesis stimulation on ERFE secretion in humans is poorly understood. This paucity of information is due in part to the lack of available means for ERFE quantification in serum samples. The present study tested a new sensitive sandwich immunoassay for human ERFE. This assay was used to demonstrate that injection of various erythropoiesis stimulating agents (ESAs) increased the blood ERFE levels in healthy volunteers. After exogenous stimulation of erythropoiesis, ERFE increased up to 8-fold with a detection window of 13 days. The impact of one unit of blood withdrawal on erythropoiesis stimulation of ERFE was also tested. ERFE significantly increased after blood withdrawal in subjects injected with both iron and saline solution, suggesting that iron supplementation did not mask the ERFE increase after blood withdrawal. The effects of exercise-induced muscle damage on ERFE was assessed by comparing ERFE levels with creatine kinase levels in samples from subjects with heavy exercise loads, and determined that this was not a confounder. The ERFE assay is a sensitive means to investigate the connection between iron metabolism and erythropoiesis in humans, and to detect ESA abuse in the antidoping field.
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Effects of a diet with or without physical activity on angiopoietin-like protein 8 concentrations in overweight/obese patients with newly diagnosed type 2 diabetes: a randomized controlled trial.
Hu, H, Yuan, G, Wang, X, Sun, J, Gao, Z, Zhou, T, Yin, W, Cai, R, Ye, X, Wang, Z
Endocrine journal. 2019;(1):89-105
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Abstract
Angiopoietin-like protein 8 (ANGPTL8) is a newly discovered adipokine plays an important role in energy homoeostasis, obesity and type 2 diabetes (T2D). Although lifestyle modification in obesity and T2D is known to offer metabolic benefits, there is paucity of comprehensive data on change in ANGPTL8. We investigated the effect of lifestyle intervention on ANGPTL8 concentrations. 384 obese/overweight adults with newly diagnosed T2D were randomly assigned (1:1:1) to diet (n = 128), diet + activity (n = 128) or usual care (control, n = 128) groups. All patients received usual care. Besides, the diet group received a calorie-restricted diet aiming for a weight loss of 5-10%. The diet + activity group additionally received a pedometer-based walking program. Primary outcome was change in ANGPTL8 concentration at 6 months. Data were analyzed according to intention-to-treat. From baseline to 6 months, the median ANGPTL8 level changed from 804.38 pg/mL to 792.86 pg/mL in control group. Compared with control, ANGPTL8 decreased with diet (baseline-adjusted between-group difference was -121.00 pg/mL, 95% CI -177.47 to -64.53; p < 0.0001) and diet + activity (-126.16 pg/mL, -181.21 to -71.11; p < 0.0001). There was no greater effect of diet + activity compared with diet (-5.16 pg/mL, -53.63 to 43.31; p = 0.8348). Both effects disappeared after adjusting for change in body fat, but did not differ significantly when adjusting for physical activity. A 6-month intervention inducing weight loss by a calorie-restricted diet or diet + activity, resulted in significant decrease on ANGPTL8 concentration. These effects were established by change in total body fat, and not by change in physical activity.
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Racial Variations in Appetite-Related Hormones, Appetite, and Laboratory-Based Energy Intake from the E-MECHANIC Randomized Clinical Trial.
Dorling, JL, Church, TS, Myers, CA, Höchsmann, C, White, UA, Hsia, DS, Martin, CK, Apolzan, JW
Nutrients. 2019;(9)
Abstract
African Americans (AAs) have a higher obesity risk than Whites; however, it is unclear if appetite-related hormones and food intake are implicated. We examined differences in appetite-related hormones, appetite, and food intake between AAs (n = 53) and Whites (n = 111) with overweight or obesity. Participants were randomized into a control group or into supervised, controlled exercise groups at 8 kcal/kg of body weight/week (KKW) or 20 KKW. Participants consumed lunch and dinner at baseline and follow-up, with appetite and hormones measured before and after meals (except leptin). At baseline, AAs had lower peptide YY (PYY; p < 0.01) and a blunted elevation in PYY after lunch (p = 0.01), as well as lower ghrelin (p = 0.02) and higher leptin (p < 0.01) compared to Whites. Despite desire to eat being lower and satisfaction being higher in AAs relative to Whites (p ≤ 0.03), no racial differences in food intake were observed. Compared to Whites, leptin increased in the 8 KKW group in AAs (p = 0.01), yet no other race-by-group interactions were evident. Differences in appetite-related hormones between AAs and Whites exist; however, their influence on racial disparities in appetite, food intake, and obesity within this trial was limited.
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Plasma Free Amino Acid Responses to Whey Protein and Their Relationships with Gastric Emptying, Blood Glucose- and Appetite-Regulatory Hormones and Energy Intake in Lean Healthy Men.
Elovaris, RA, Hutchison, AT, Lange, K, Horowitz, M, Feinle-Bisset, C, Luscombe-Marsh, ND
Nutrients. 2019;(10)
Abstract
This study determined the effects of increasing loads of whey protein on plasma amino acid (AA) concentrations, and their relationships with gastric emptying, blood glucose- and appetite-regulatory hormones, blood glucose and energy intake. Eighteen healthy lean men participated in a double-blinded study, in which they consumed, on 3 separate occasions, in randomised order, 450-mL drinks containing either 30 g (L) or 70 g (H) of pure whey protein isolate, or control with 0 g of protein (C). Gastric emptying, serum concentrations of AAs, ghrelin, cholecystokinin (CCK), glucagon-like-peptide 1 (GLP-1), insulin, glucagon and blood glucose were measured before and after the drinks over 180 min. Then energy intake was quantified. All AAs were increased, and 7/20 AAs were increased more by H than L. Incremental areas under the curve (iAUC0-180 min) for CCK, GLP-1, insulin and glucagon were correlated positively with iAUCs of 19/20 AAs (p < 0.05). The strongest correlations were with the branched-chain AAs as well as lysine, tyrosine, methionine, tryptophan, and aspartic acid (all R2 > 0.52, p < 0.05). Blood glucose did not correlate with any AA (all p > 0.05). Ghrelin and energy intake correlated inversely, but only weakly, with 15/20 AAs (all R2 < 0.34, p < 0.05). There is a strong relationship between gluco-regulatory hormones with a number of (predominantly essential) AAs. However, the factors mediating the effects of protein on blood glucose and energy intake are likely to be multifactorial.
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Effect of Oral Nutritional Supplements with Sucromalt and Isomaltulose versus Standard Formula on Glycaemic Index, Entero-Insular Axis Peptides and Subjective Appetite in Patients with Type 2 Diabetes: A Randomised Cross-Over Study.
Angarita Dávila, L, Bermúdez, V, Aparicio, D, Céspedes, V, Escobar, MC, Durán-Agüero, S, Cisternas, S, de Assis Costa, J, Rojas-Gómez, D, Reyna, N, et al
Nutrients. 2019;(7)
Abstract
Oral diabetes-specific nutritional supplements (ONS-D) induce favourable postprandial responses in subjects with type 2 diabetes (DM2), but they have not been correlated yet with incretin release and subjective appetite (SA). This randomised, double-blind, cross-over study compared postprandial effects of ONS-D with isomaltulose and sucromalt versus standard formula (ET) on glycaemic index (GI), insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1) and SA in 16 individuals with DM2. After overnight fasting, subjects consumed a portion of supplements containing 25 g of carbohydrates or reference food. Blood samples were collected at baseline and at 30, 60, 90, 120, 150 and 180 min; and SA sensations were assessed by a visual analogue scale on separate days. Glycaemic index values were low for ONS-D and intermediate for ET (p < 0.001). The insulin area under the curve (AUC0-180 min) (p < 0.02) and GIP AUC (p < 0.02) were lower after ONS-D and higher GLP-1 AUC when compared with ET (p < 0.05). Subjective appetite AUC was greater after ET than ONS-D (p < 0.05). Interactions between hormones, hunger, fullness and GI were found, but not within the ratings of SA; isomaltulose and sucromalt may have influenced these factors.
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Postprandial effects of consuming a staggered meal on gut peptide and glycemic responses in obese women and men.
Griffith, L, Haddad, EH, Tonstad, S
Obesity research & clinical practice. 2016;(3):264-74
Abstract
Eating slowly by staggering a meal may reduce energy intake. Our aim was to examine the effect of eating a portion of beans 15min before the rest of the meal, on gastrointestinal (GI) peptides, glucose and insulin concentrations and subsequent energy intake in obese adults. This was a randomised crossover design study with 28 obese subjects. Participants consumed a standardised breakfast on test days followed by test meals: (1) control meal containing 86g (0.5 cup) of beans, and (2) staggered meal in which 86g (0.5 cup) of beans were consumed 15min before the rest of the meal. Blood obtained prior to and at 30, 60, and 120min following the meals was analysed for acylated ghrelin, unacylated ghrelin, glucagon-like peptide-1 (GLP-1), peptide YY, oxyntomodulin, glucose and insulin. Feelings of hunger and satiety were assessed using analog visual scales. Energy intake following the test meal was obtained by computer assisted dietary recalls. Mixed model statistical analysis of data showed time effects for unacylated ghrelin, GLP-1, glucose, insulin, hunger and fullness, however, meal effects were not shown for any of the parameters. GLP-1 area under the curve from baseline to 120min (AUC0-120) decreased by 19% (P=0.024) and that of glucose increased by 7% (P=0.046) following the staggered compared to the control bean meal. Energy intake subsequent to the test meals did not differ between treatments. In conclusion, lengthening meal times by staggering eating did not benefit hormonal, metabolic or appetite control in obese individuals.
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Dietary whey protein influences plasma satiety-related hormones and plasma amino acids in normal-weight adult women.
Chungchunlam, SM, Henare, SJ, Ganesh, S, Moughan, PJ
European journal of clinical nutrition. 2015;(2):179-86
Abstract
BACKGROUND/OBJECTIVE A distinct suppressive effect of a whey protein (including glycomacropeptide)-enriched preload drink on subsequent food intake in comparison with a maltodextrin carbohydrate-enriched preload was demonstrated in an earlier companion study with the same female subjects; however, the potential mediators underlying the effect are unclear. The objective of this study was to investigate how the ingestion of a whey protein-enriched preload beverage affected postprandial plasma concentrations of several satiety-related gastrointestinal hormones and metabolites in comparison with a maltodextrin carbohydrate-enriched preload. SUBJECTS/METHODS Eighteen normal-weight women were studied in a single-blind, randomized block design. Blood samples were collected at various time intervals for 120 min after consumption of a test drink (300 ml, ~1300 kJ) enriched (45 g) with either maltodextrin carbohydrate or whey protein containing naturally present glycomacropeptide. RESULTS Plasma-active ghrelin concentrations decreased after both maltodextrin carbohydrate- and whey protein-enriched test drinks (P<0.05). The whey protein-enriched beverage led to increased plasma concentrations of cholecystokinin (CCK) at 60 and 75 min (P<0.05), glucagon-like peptide-1 (GLP-1) at 90 min (P<0.001), peptide tyrosine-tyrosine (PYY) at 90 and 120 min (P<0.01) and pancreatic polypeptide (PP) from 15 to 120 min (P<0.05) compared with maltodextrin carbohydrate. Total amino acid, urea and ammonia plasma concentrations were also higher after whey protein compared with maltodextrin carbohydrate ingestion (P<0.01). CONCLUSIONS Increased plasma concentrations of some gastrointestinal hormones related to satiety, particularly PP, and of amino acids and their metabolites, may have acted either singly or together to mediate the observed satiety response to whey protein.