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Acute effects of delayed-release hydrolyzed pine nut oil on glucose tolerance, incretins, ghrelin and appetite in healthy humans.
Sørensen, KV, Korfitzen, SS, Kaspersen, MH, Ulven, ER, Ekberg, JH, Bauer-Brandl, A, Ulven, T, Højlund, K
Clinical nutrition (Edinburgh, Scotland). 2021;(4):2169-2179
Abstract
BACGROUND & AIM: Pinolenic acid, a major component (~20%) of pine nut oil, is a dual agonist of the free fatty acid receptors, FFA1 and FFA4, which may regulate release of incretins and ghrelin from the gut. Here, we investigated the acute effects of hydrolyzed pine nut oil (PNO-FFA), delivered to the small intestine by delayed-release capsules, on glucose tolerance, insulin, incretin and ghrelin secretion, and appetite. METHODS In two cross-over studies, we evaluated 3 g unhydrolyzed pine nut oil (PNO-TG) or 3 g PNO-FFA versus no oil in eight healthy, non-obese subjects (study 1), and 3 g PNO-FFA or 6 g PNO-FFA versus no oil in ten healthy, overweight/obese subjects (study 2) in both studies given in delayed-release capsules 30 min prior to a 4-h-oral glucose tolerance test (OGTT). Outcomes were circulating levels of glucose, insulin, GLP-1, GIP, ghrelin, appetite and gastrointestinal tolerability during OGTT. RESULTS Both 3 g PNO-FFA in study 1 and 6 g PNO-FFA in study 2 markedly increased GLP-1 levels (p < 0.001) and attenuated ghrelin levels (p < 0.001) during the last 2 h of the OGTT compared with no oil. In study 2, these effects of PNO-FFA were accompanied by an increased satiety and fullness (p < 0.03), and decreased prospective food consumption (p < 0.05). PNO-FFA caused only small reductions in glucose and insulin levels during the first 2 h of the OGTT. CONCLUSIONS Our results provide evidence that PNO-FFA delivered to the small intestine by delayed-release capsules may reduce appetite by augmenting GLP-1 release and attenuating ghrelin secretion in the late postprandial state. CLINICAL TRIAL REGISTRY NUMBERS NCT03062592 and NCT03305367.
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LEAP-2/ghrelin interplay in adult growth hormone deficiency: Cause or consequence? A pilot study.
Vergani, E, Bruno, C, Gavotti, C, Aversa, LS, Martire, M, Mancini, A, Currò, D
IUBMB life. 2021;(7):978-984
Abstract
Ghrelin and its endogenous antagonist liver-expressed antimicrobial peptide-2 (LEAP-2) are involved in GH secretion and glucose/lipids metabolism. LEAP-2 expression in conditions of metabolic impairment may be upregulated, usually pairing with a concomitant reduction in ghrelin secretion. Adult growth hormone deficiency (aGHD) is characterized by insulin resistance, weight gain, and increased fat mass. Therefore, the primary endpoint of this cross-sectional observational pilot study was to compare circulating LEAP-2 and ghrelin levels in aGHD and healthy controls. Thirty patients were included in the study. Group A included adult GHD: 15 patients, 8 females, and 7 males. Median and interquartile range age of the group was 53 (41-57) years, while BMI was 27.1 (25-35) kg/m2 . Group B was formed by 15 healthy controls (10 females and 5 males). Median and interquartile range age was 47 (36-57) years, while BMI 22.9 (20.8-33.1) kg/m2 . They were evaluated for serum glucose and insulin, HOMA-index, QUICKI-index, total/LDL/HDL cholesterol, triglycerides, IGF-1, ghrelin, and LEAP-2. Ghrelin levels in the aGHD group were significantly lower than in healthy controls. In contrast, LEAP-2 showed a trend toward higher levels, although the differences were not significant. However, the LEAP-2/Ghrelin ratio was significantly higher in aGHD. No significant correlations between ghrelin and LEAP-2 with BMI and HOMA index were found in aGHD population. However, a significant inverse correlation (r2 = 0.15, p = .047) between BMI and ghrelin was evidenced when considering the whole population. Taken together, these results may suggest a body adaptation to a metabolic scenario typical of aGHD. The decrease in ghrelin production could prevent further weight gain and fat mass increase, although losing its secretagogue effect.
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Six-month changes in ghrelin and glucagon-like peptide-1 with weight loss are unrelated to long-term weight regain in obese older adults.
Rejeski, JJ, Fanning, J, Nicklas, BJ, Rejeski, WJ
International journal of obesity (2005). 2021;(4):888-894
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Abstract
BACKGROUND AND OBJECTIVE Weight loss (WL) and subsequent regain are complex physiologic processes, and our understanding of the hormonal changes associated with these processes continues to evolve. We aimed to examine the effects of behavioral WL on 6-month changes in ghrelin and GLP-1 and evaluate the effects of these changes in gut hormones on weight regain among older adults. SUBJECTS AND METHODS One hundred seventy-seven obese (BMI: 33.5 (3.5) kg/m2) older adults (66.9 ± 4.7 years, 71.2% female, 67.6% white) were randomized to WL (WL; n = 68), WL plus aerobic training (n = 79), or WL plus resistance training (n = 75) for 18 months. Ghrelin, GLP-1, power of food scale (PFS), and weight were measured at baseline, 6 months, and 18 months. RESULTS There was no differential treatment effect on change in either gut hormone, however, there was a significant time effect across all groups (p < 0.001), with increases in ghrelin (∆ = +106.77 pg/ml; 95% CI = + 84.82, +128.71) and decreases in GLP-1 (∆ = -4.90 pM; 95% CI = -6.27, -3.51) at 6-month. Ratings on the PFS decreased from baseline to 6-month and there was significant loss of weight from baseline to either 6- or 18-month, ∆ = -7.96 kg; 95% CI = -7.95, -8.78 and ∆ = -7.80 kg; 95% CI = -8.93, -6.65, respectively (p < 0.001). Changes in ghrelin and GLP-1 at 6-month did not predict weight regain from 6- to 18-month. DISCUSSION AND CONCLUSION Among older adults with obesity and cardiometabolic disease, the intensive phase of dietary WL results in increasing levels of ghrelin and decreasing levels of GLP-1 that are unrelated to weight regain a year later. Registered with ClinicalTrials.gov (NCT01547182).
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Higher unacylated ghrelin and insulin sensitivity following dietary restriction and weight loss in obese humans.
Barazzoni, R, Gortan Cappellari, G, Zanetti, M, Klaus, KA, Semolic, A, Johnson, ML, Nair, KS
Clinical nutrition (Edinburgh, Scotland). 2021;(2):638-644
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BACKGROUND & AIMS Unacylated ghrelin (UnAG) modulates insulin sensitivity. Low plasma UnAG occurs in obesity and potentially contributes to obesity-associated insulin resistance. We hypothesized that improvements in insulin sensitivity in obese people induced by moderate caloric restriction (CR) may be paralleled and at least in part explained by concurrent increases in UnAG levels. METHODS 20 general community obese people were randomly assigned to 16-week CR (n = 11) or control diet (n = 9). We investigated the impact of CR on the interaction between insulin sensitivity changes [area under the curve (AUCg) of glucose infusion to maintain euglycemia during hyperinsulinemic-euglycemic clamp] and plasma total (TotalG), acylated (AG) and Unacylated ghrelin (UnAG). Plasma pro-inflammatory tumor necrosis factor alpha (TNFα) and anti-inflammatory interleukin-10 (IL-10) were also measured since changes in inflammation may contribute to UnAG activities. RESULTS CR reduced BMI and increased insulin sensitivity (p < 0.05). TotalG and UnAG but not AG increased in CR but not in Control (p < 0.05). Il-10 and IL-10/TNFα ratio also increased in CR (p < 0.05). Changes in UnAG were positively associated with changes in AUCg in all subjects (n = 20; p < 0.01) also after adjustment for treatment and changes in BMI and cytokines. CONCLUSIONS Caloric restriction modifies circulating ghrelin profile with selective increase in unacylated hormone in obese individuals. The current study supports the hypothesis that higher unacylated ghrelin contributes to improvements in insulin sensitivity following diet-induced weight loss in human obesity.
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Changes in Ghrelin and Glucagon following a Low Glycemic Load Diet in Women with PCOS.
Hoover, SE, Gower, BA, Cedillo, YE, Chandler-Laney, PC, Deemer, SE, Goss, AM
The Journal of clinical endocrinology and metabolism. 2021;(5):e2151-e2161
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CONTEXT Altered satiety hormones in women with polycystic ovarian syndrome (PCOS) may contribute to obesity. Diets with a low glycemic load (GL) may influence appetite-regulating hormones including glucagon and ghrelin. OBJECTIVE To test the hypothesis that following a 4-week, eucaloric low vs high GL diet habituation, a low vs high GL meal will increase glucagon and decrease ghrelin to reflect greater satiety and improve self-reported fullness. METHODS Secondary analysis of a randomized crossover trial. PARTICIPANTS Thirty women diagnosed with PCOS. INTERVENTION Participants were provided low (41:19:40% energy from carbohydrate:protein:fat) and high (55:18:27) GL diets for 8 weeks each. At each diet midpoint, a solid meal test was administered to examine postprandial ghrelin, glucagon, glucose, insulin, and self-reported appetite scores. RESULTS After 4 weeks, fasting glucagon was greater with the low vs high GL diet (P = .035), and higher fasting glucagon was associated with lesser feelings of hunger (P = .009). Significant diet effects indicate 4-hour glucagon was higher (P < .001) and ghrelin was lower (P = .009) after the low vs high GL meal. A trending time × diet interaction (P = .077) indicates feelings of fullness were greater in the early postprandial phase after the high GL meal, but no differences were observed the late postprandial phase. CONCLUSION These findings suggest after low GL diet habituation, a low GL meal reduces ghrelin and increases glucagon in women with PCOS. Further research is needed to determine the influence of diet composition on ad libitum intake in women with PCOS.
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Current Aspects of the Role of Autoantibodies Directed Against Appetite-Regulating Hormones and the Gut Microbiome in Eating Disorders.
Smitka, K, Prochazkova, P, Roubalova, R, Dvorak, J, Papezova, H, Hill, M, Pokorny, J, Kittnar, O, Bilej, M, Tlaskalova-Hogenova, H
Frontiers in endocrinology. 2021;:613983
Abstract
The equilibrium and reciprocal actions among appetite-stimulating (orexigenic) and appetite-suppressing (anorexigenic) signals synthesized in the gut, brain, microbiome and adipose tissue (AT), seems to play a pivotal role in the regulation of food intake and feeding behavior, anxiety, and depression. A dysregulation of mechanisms controlling the energy balance may result in eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). AN is a psychiatric disease defined by chronic self-induced extreme dietary restriction leading to an extremely low body weight and adiposity. BN is defined as out-of-control binge eating, which is compensated by self-induced vomiting, fasting, or excessive exercise. Certain gut microbiota-related compounds, like bacterial chaperone protein Escherichia coli caseinolytic protease B (ClpB) and food-derived antigens were recently described to trigger the production of autoantibodies cross-reacting with appetite-regulating hormones and neurotransmitters. Gut microbiome may be a potential manipulator for AT and energy homeostasis. Thus, the regulation of appetite, emotion, mood, and nutritional status is also under the control of neuroimmunoendocrine mechanisms by secretion of autoantibodies directed against neuropeptides, neuroactive metabolites, and peptides. In AN and BN, altered cholinergic, dopaminergic, adrenergic, and serotonergic relays may lead to abnormal AT, gut, and brain hormone secretion. The present review summarizes updated knowledge regarding the gut dysbiosis, gut-barrier permeability, short-chain fatty acids (SCFA), fecal microbial transplantation (FMT), blood-brain barrier permeability, and autoantibodies within the ghrelin and melanocortin systems in eating disorders. We expect that the new knowledge may be used for the development of a novel preventive and therapeutic approach for treatment of AN and BN.
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Involvement of Ghrelin Dynamics in Stress-Induced Eating Disorder: Effects of Sex and Aging.
Yamada, C
International journal of molecular sciences. 2021;(21)
Abstract
Stress, a factor that affects appetite in our daily lives, enhances or suppresses appetite and changes palatability. However, so far, the mechanisms underlying the link between stress and eating have not been fully elucidated. Among the peripherally produced appetite-related peptides, ghrelin is the only orexigenic peptide, and abnormalities in the dynamics and reactivity of this peptide are involved in appetite abnormalities in various diseases and psychological states. This review presents an overview of the research results of studies evaluating the effects of various stresses on appetite. The first half of this review describes the relationship between appetite and stress, and the second half describes the relationship between the appetite-promoting peptide ghrelin and stress. The effects of sex differences and aging under stress on appetite are also described.
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Dairy products influence gut hormone secretion and appetite differently: A randomized controlled crossover trial.
Hansson, P, Holven, KB, Øyri, LKL, Brekke, HK, Gjevestad, GO, Rehfeld, JF, Raza, GS, Herzig, KH, Ulven, SM
Journal of dairy science. 2020;(2):1100-1109
Abstract
Little is known about how dairy products with different nutrient contents and food matrices affect appetite sensation and gut hormone secretion. The objective of this study was to investigate how appetite sensation and gut hormone secretion in healthy adults are affected by meals with the same amount of fat but from different dairy products. Forty-seven healthy adults (70% women) were recruited to a randomized controlled crossover study with 4 dairy meals consisting of butter, cheese, whipped cream, or sour cream, corresponding to 45 g (approximately 60 energy percent) of fat. Plasma samples were collected for analysis of cholecystokinin (CCK), pancreatic polypeptide (PP), peptide YY (PYY), and ghrelin concentrations at 0, 2, 4, and 6 h after the meals and analyzed as the incremental area under the curve (iAUC0-6h) in a mixed model. Hunger, satiety, and appetite sensations were measured with a visual analog scale (VAS) immediately after finishing the meals and at 4 and 6 h postprandially. Intake of cheese induced a higher level of plasma PP-iAUC0-6h compared with butter or whipped cream, and a higher level of plasma CCK-iAUC0-6h compared with whipped cream. Intake of whipped cream increased VAS appetite at 4 h compared with cheese or sour cream, and at 6 h compared with cheese or butter. No significant meal effect was found for hunger, satiety, plasma PYY, or plasma ghrelin concentration. Intake of cheese increased postprandial plasma PP and CCK concentrations and decreased appetite compared with whipped cream but not with sour cream. These findings encourage further investigations of how different dairy products affect gut hormone secretion and appetite sensation.
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How oro-sensory exposure and eating rate affect satiation and associated endocrine responses-a randomized trial.
Lasschuijt, M, Mars, M, de Graaf, C, Smeets, PAM
The American journal of clinical nutrition. 2020;(6):1137-1149
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BACKGROUND Longer oral processing decreases food intake. This can be attributed to greater oro-sensory exposure (OSE) and a lower eating rate (ER). How these factors contribute to food intake, and the underlying physiological mechanisms, remain unclear. OBJECTIVES We aimed to determine the independent and simultaneous effects of OSE and ER on satiation and associated endocrine responses. METHODS Forty participants in study 1 [mean ± SD age: 24 ± 4 y; BMI (in kg/m2): 22 ± 2] and 20 in study 2 (mean ± SD age: 23 ± 3 y; BMI: 23 ± 2) participated in a 2 × 2 randomized trial. In both studies, participants ate chocolate custard with added caramel sauce (low OSE) or caramel fudge (high OSE) and with short (fast ER) or long breaks (slow ER) in between bites, until fullness. In study 2, endocrine responses were measured during the meal. RESULTS In study 1, participants ate (mean ± SEM) 42 ± 15 g less in the slow- than in the fast-ER condition, only within the high-OSE condition (P = 0.04). In study 2, participants ate 66 ± 21 g less in the high- than in the low-OSE condition and there were no intake differences between slow and fast ER (P = 0.35). Eight minutes after starting to eat, insulin concentrations increased by 42%-65% in all treatments compared with the control. At the end of the meal, insulin concentrations were 81% higher in the high-OSE, slow-ER than in the low-OSE, fast-ER condition (P = 0.049). Pancreatic polypeptide (PP) increased by 62%, 5 min after meal onset in the low-OSE, fast-ER condition (P = 0.005). Ghrelin concentrations did not change. CONCLUSIONS Greater OSE increases insulin responsiveness. In contrast, PP responses are stronger when OSE is reduced and ER is fast. Insulin and PP responses may mediate the independent effects of OSE and ER on food intake. These may be beneficial eating strategies, particularly for type 2 diabetic patients, to control food intake and maintain glucose homeostasis.This trial was registered at trialregister.nl as NL6544.
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Influence of Short-Term Hyperenergetic, High-Fat Feeding on Appetite, Appetite-Related Hormones, and Food Reward in Healthy Men.
Thackray, AE, Willis, SA, Clayton, DJ, Broom, DR, Finlayson, G, Goltz, FR, Sargeant, JA, Woods, RM, Stensel, DJ, King, JA
Nutrients. 2020;(9)
Abstract
Short-term overfeeding may provoke compensatory appetite responses to correct the energy surplus. However, the initial time-course of appetite, appetite-related hormone, and reward-related responses to hyperenergetic, high-fat diets (HE-HFD) are poorly characterised. Twelve young healthy men consumed a HE-HFD (+50% energy, 65% fat) or control diet (36% fat) for seven days in a randomised crossover design. Mean appetite perceptions were determined during an oral glucose tolerance test (OGTT) before and after each diet. Fasted appetite perceptions, appetite-related hormones, and reward parameters were measured pre-diet and after 1-, 3- and 7-days of each diet. The HE-HFD induced a pre-to-post diet suppression in mean appetite during the OGTT (all ratings p ≤ 0.058, effect size (d) ≥ 0.31), and reduced the preference for high-fat vs. low-fat foods (main effect diet p = 0.036, d = 0.32). Fasted leptin was higher in the HE-HFD than control diet (main effect diet p < 0.001, d = 0.30), whilst a diet-by-time interaction (p = 0.036) revealed fasted acylated ghrelin was reduced after 1-, 3- and 7-days of the HE-HFD (all p ≤ 0.040, d ≥ 0.50 vs. pre-diet). Appetite perceptions and total peptide YY in the fasted state exhibited similar temporal patterns between the diets (diet-by-time interaction p ≥ 0.077). Seven days of high-fat overfeeding provokes modest compensatory changes in subjective, hormonal, and reward-related appetite parameters.