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1.
Comparative effects of intraduodenal protein and lipid on ghrelin, peptide YY, and leptin release in healthy men.
Ullrich, SS, Otto, B, Hutchison, AT, Luscombe-Marsh, ND, Horowitz, M, Feinle-Bisset, C
American journal of physiology. Regulatory, integrative and comparative physiology. 2015;(4):R300-4
Abstract
Intraduodenal infusion of lipid or protein potently reduces subsequent energy intake. There is evidence that the underlying mechanisms differ significantly between the two nutrients. While intraduodenal lipid stimulates glucagon-like peptide-1 and CCK much more than protein, the release of insulin and glucagon is substantially greater in response to protein. Ghrelin and PYY are both involved in short-term regulation, while leptin is a long-term regulator, of energy balance; the acute effects of nutrients on leptin release are unclear. We investigated the comparative effects of intraduodenal lipid and protein on plasma ghrelin, PYY, and leptin concentrations. Thirteen lean, young men received 90-min intraduodenal infusions of protein (whey hydrolysate) or lipid (long-chain triglyceride emulsion) at a rate of 3 kcal/min, or saline control, on three separate days. Blood samples were collected at baseline and regularly during infusions. Both lipid and protein potently suppressed plasma ghrelin compared with control (both P < 0.001), with no difference between them. While both lipid and protein stimulated plasma PYY (P < 0.001), the effect of lipid was substantially greater than that of protein (P < 0.001). Neither intraduodenal lipid nor protein affected plasma leptin. In conclusion, intraduodenal lipid and protein have discrepant effects on the release of PYY, but not ghrelin. When considered with our previous findings, it appears that, with the exception of ghrelin, the energy intake-suppressant effects of lipid and protein are mediated by different mechanisms.
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Appetite, appetite hormone and energy intake responses to two consecutive days of aerobic exercise in healthy young men.
Douglas, JA, King, JA, McFarlane, E, Baker, L, Bradley, C, Crouch, N, Hill, D, Stensel, DJ
Appetite. 2015;:57-65
Abstract
Single bouts of exercise do not cause compensatory changes in appetite, food intake or appetite regulatory hormones on the day that exercise is performed. It remains possible that such changes occur over an extended period or in response to a higher level of energy expenditure. This study sought to test this possibility by examining appetite, food intake and appetite regulatory hormones (acylated ghrelin, total peptide-YY, leptin and insulin) over two days, with acute bouts of exercise performed on each morning. Within a controlled laboratory setting, 15 healthy males completed two, 2-day long (09:00-16:00) experimental trials (exercise and control) in a randomised order. On the exercise trial participants performed 60 min of continuous moderate-high intensity treadmill running (day one: 70.1 ± 2.5% VO2peak, day two: 70.0 ± 3.2% VO2max (mean ± SD)) at the beginning of days one and two. Across each day appetite perceptions were assessed using visual analogue scales and appetite regulatory hormones were measured from venous blood samples. Ad libitum energy and macronutrient intakes were determined from meals provided two and six hours into each day and from a snack bag provided in-between trial days. Exercise elicited a high level of energy expenditure (total = 7566 ± 635 kJ across the two days) but did not produce compensatory changes in appetite or energy intake over two days (control: 29,217 ± 4006 kJ; exercise: 28,532 ± 3899 kJ, P > 0.050). Two-way repeated measures ANOVA did not reveal any main effects for acylated ghrelin or leptin (all P > 0.050). However a significant main effect of trial (P = 0.029) for PYY indicated higher concentrations on the exercise vs. control trial. These findings suggest that across a two day period, high volume exercise does not stimulate compensatory appetite regulatory changes.
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Effect of methylphenidate treatment on appetite and levels of leptin, ghrelin, adiponectin, and brain-derived neurotrophic factor in children and adolescents with attention deficit and hyperactivity disorder.
Sahin, S, Yuce, M, Alacam, H, Karabekiroglu, K, Say, GN, Salıs, O
International journal of psychiatry in clinical practice. 2014;(4):280-7
Abstract
OBJECTIVES We aimed to explore whether the use of methylphenidate relates leptin, ghrelin, adiponectin, and brain-derived neurotrophic factor (BDNF). In addition, the relationship between methylphenidate-related weight loss in attention deficit hyperactivity disorder (ADHD) patients and these biomolecules were evaluated. METHODS Thirty ADHD patients receiving methylphenidate and 20 healthy controls were included. Leptin, ghrelin, adiponectin, and BDNF levels were measured at baseline and after two-month treatment in both groups. RESULTS At baseline, leptin, ghrelin, adiponectin, and BDNF levels were similar in the ADHD and control groups. The most common adverse events occurring in the ADHD group after a 2-month treatment period included loss of appetite (70%) and weight loss (66.7%). A significant difference was found in body weight, BMI, and CGI scores of the ADHD patients after the treatment. While post-treatment ghrelin and adiponectin levels were significantly higher in the ADHD group, BDNF level was significantly lower. Post-treatment decrease in leptin levels was not significant. CONCLUSIONS Leptin and BDNF were not associated with poor appetite and/or weight loss due to methylphenidate treatment. However, ghrelin and adiponectin might be biomolecules that play a role in underlying neurobiological mechanisms of methylphenidate-related appetite or weight loss.
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Differential influences of gastric bypass and sleeve gastrectomy on plasma nesfatin-1 and obestatin levels in patients with type 2 diabetes mellitus.
Lee, WJ, Chen, CY, Ser, KH, Chong, K, Chen, SC, Lee, PC, Liao, YD, Lee, SD
Current pharmaceutical design. 2013;(32):5830-5
Abstract
OBJECTIVE The mechanisms by which bariatric surgeries, including gastric bypass (GB) and sleeve gastrectomy (SG), achieve remission of type 2 diabetes mellitus (T2DM) and sustained weight reduction are unknown. We hypothesized that the novel anorexic hormone nesfatin-1 and another new hormone obestatin might contribute to the marked improvement in glycemic homeostasis and weight loss in diabetics after GB and SG. METHODS A hospital-based, prospective study was conducted. Overnight fasting plasma concentrations of nesfatin-1 and obestatin were analyzed in T2DM patients before surgery, and at 3 and 12 months after laparoscopic GB (n =12) and SG (n = 6). RESULTS At 12 months, reductions of body mass index (BMI), fasting blood glucose, and glycated hemoglobin were similar between GB and SG groups (P all > 0.05). Plasma nesfatin-1 levels in patients undergoing GB or SG significantly decreased after surgeries (P both < 0.05). In contrast, plasma obestatin concentrations significantly increased in patients after SG (P < 0.05) but without any alteration after GB. The alterations of plasma nesfatin-1 were significantly and negatively associated with the reduction of fasting blood glucose (P <0.05) at 12 months after GB and SG. In the SG group, the reduction of nesfatin-1 significantly and positively correlated with the decrease of BMI (P < 0.05). CONCLUSIONS GB and SG produce differential influences with regards to circulating nesfatin-1 and obestatin levels in non-morbidly obese, T2DM patients. Circulating nesfatin-1 may modulate glucose homeostasis in two surgical procedures, and participate in regulating body weight in SG.
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Effects of L-thyroxine on gastric motility and ghrelin in subclinical hypothyroidism: a prospective study.
Canpolat, AG, Kav, T, Sivri, B, Yildiz, BO
The Journal of clinical endocrinology and metabolism. 2013;(11):E1775-9
Abstract
INTRODUCTION Overt hypothyroidism affects the gastrointestinal system. Limited data are available regarding gastric motility in subclinical hypothyroidism (SCH). OBJECTIVE The aim of this study was to assess gastric motility-related gastric symptoms and levels of ghrelin in patients with SCH compared with those in healthy control subjects and to evaluate the potential effects of l-thyroxine replacement therapy. METHODS Twenty premenopausal women with SCH and 20 age- and body mass index-matched healthy control women were enrolled in the study. The gastroparesis cardinal severity index questionnaire was used to reveal gastrointestinal motility changes, and electrogastrographic activities were measured. Fasting and postprandial ghrelin levels at 30, 60, and 120 minutes were determined during a mixed meal test. All tests were repeated after 6 months when patients were in the euthyroid state. RESULTS The gastroparesis cardinal severity index score, fasting tachygastria ratio, and postprandial/fasting bradygastria ratio in electrogastrography were higher in patients with SCH compared with control subjects (P = .03, P = .04, and P = .04, respectively). All 3 parameters significantly improved after l-thyroxine replacement therapy (P < .001, P = .005, and P =.02 respectively) reaching levels similar to those of control subjects. Baseline and area under the curve for ghrelin during mixed meal tests did not show a difference between patients with SCH and control subjects and before and after l-thyroxine replacement in SCH. CONCLUSION Gastric dysmotility and the resultant upper gastrointestinal symptoms can be observed in SCH, and symptomatology related to dysmotility and parameters appear to be improved with thyroid hormone replacement. Our results also suggest that ghrelin levels in response to a meal are similar between women with SCH and healthy women and that normalization of thyroid function by l-thyroxine does not modulate these levels.
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Desacyl ghrelin is influenced by changes in insulin concentration during an insulin tolerance test.
Blijdorp, K, van der Lely, AJ, van den Heuvel-Eibrink, MM, Huisman, TM, Themmen, AP, Delhanty, PJ, Neggers, SJ
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2013;(5):193-5
Abstract
OBJECTIVE Ghrelin, a gut-brain peptide, regulates energy homeostasis and glucose metabolism and is present in acylated and nonacylated form in the circulation. Although desacyl ghrelin (DAG), the predominant form of ghrelin, is associated with insulin sensitivity and improved metabolic state, not much is known about its direct regulation by insulin. We aimed to assess changes in DAG in response to the rapid increase in insulin concentration during an insulin tolerance test (ITT) in normal weight and obese subjects. DESIGN We performed an observational single center study. An ITT was assessed in eight subjects (four males), median age of 29.9 years (range 19.6-42.0). DAG concentrations were measured at 20, 40, 60 and 90 min after insulin infusion. Homeostatic Model Assessment (HOMA) was calculated from fasting insulin and glucose. Body mass index (BMI) and waist circumference were assessed. RESULTS Three subjects were obese (BMI ≥ 30 kg/m(2)), one subject was overweight (BMI = 25-30 kg/m(2)) and four subjects had normal weight (BMI = 18.5-25 kg/m(2)). Median DAG decreased after insulin infusion (90 pg/mL, p = 0.028), especially in normal weight subjects. Baseline DAG was lower in subjects with higher BMI (ρ = -0.76, p = 0.028) and higher fasting insulin (ρ = -0.76, p = 0.030). DAG changes correlated with fasting insulin levels (ρ = -0.85, p = 0.007), HOMA (ρ = -0.86, p = 0.007), BMI (ρ = -0.83, p = 0.010) and waist circumference (ρ = -0.93, p < 0.001). CONCLUSION DAG levels rapidly decreased in response to insulin administration in normal subjects, but not in insulin-resistant obese who are in a state of relative DAG deficiency.
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The impact of insulin-independent, glucagon-induced suppression of total ghrelin on satiety in obesity and type 1 diabetes mellitus.
Arafat, AM, Weickert, MO, Adamidou, A, Otto, B, Perschel, FH, Spranger, J, Möhlig, M, Pfeiffer, AF
The Journal of clinical endocrinology and metabolism. 2013;(10):4133-42
Abstract
AIMS/HYPOTHESIS The mechanisms underlying glucagon-induced satiety are incompletely understood. The glucagon-induced reduction in total ghrelin exerted at the hypothalamo-pituitary level might be responsible for this effect. Here we investigated glucagon-suppressive effects on circulating total and acyl-ghrelin, both in obesity and in type 1 diabetes mellitus (T1DM), with respect to the role of glucagon in appetite control. We further aimed to identify a possible mechanistic impact of changes in endogenous insulin. METHODS In our prospective, double-blinded, placebo-controlled study, we investigated the endocrine and metabolic responses to intramuscular glucagon administration in 13 patients with T1DM (6 males, 7 females; body mass index [BMI] 24.8 ± 0.95 kg/m(2)), 11 obese participants (OP; 5 males, 6 females; BMI 34.4 ± 1.7 kg/m(2)), and 13 healthy lean participants (LP; 6 males, 7 females; BMI 21.7 ± 0.6 kg/m(2)). RESULTS As compared with placebo, glucagon significantly increased satiety index in T1DM and in LP (P < .001) but failed to induce satiety in OP (P = .152). Total ghrelin significantly decreased after glucagon administration in all study groups (P < .01). Similarly, acyl-ghrelin significantly decreased in LP (P < .01). However, acyl-ghrelin concentrations showed no change in OP (P = .248) and even increased substantially in T1DM (P < .01). Changes in acyl-ghrelin correlated positively with changes in nonesterified fatty acid concentrations in all groups (r = 0.31-0.43; P < .01). CONCLUSIONS/INTERPRETATION Glucagon-induced satiety was preserved in T1DM but not in obesity. This effect was unrelated to changes in total or acylated ghrelin and was independent of endogenous insulin release. In contrast to the insulin-independent glucagon-induced suppression of total ghrelin, glucagon- and/or insulin-induced modification of lipolysis may determine changes in acylated ghrelin.
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Effects of habitual diet on ethnic differences in serum total ghrelin.
Ellis, AC, Chandler-Laney, P, Casazza, K, Goree, LL, Gower, BA
Endocrine. 2012;(2):359-65
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Abstract
Ghrelin, an orexigenic hormone, may be involved in the etiology of obesity. African Americans (AA) experience higher obesity rates than European Americans (EA), but it is unclear whether ghrelin differs with ethnicity. This study was designed to compare ghrelin concentrations between overweight AA and EA adults in a post absorptive state, in response to a standard meal, and after 8-week habituation to diets of differing macronutrient profiles. Sixty-one overweight men and women (31 EA and 30 AA) were assigned to either a higher-carbohydrate/lower-fat diet (55% CHO, 18% PRO, 27% FAT) or a lower-carbohydrate/higher-fat diet (43% CHO, 18% PRO, 39% FAT) for 8 weeks. At baseline and week 8, participants ingested a standard liquid mixed meal. Blood was sampled before the meal and serially after ingestion to measure total ghrelin and insulin. Hunger was assessed with a visual analog scale. Composite scores for ghrelin, insulin, and hunger were calculated as area under the curve (AUC), and ghrelin suppression was calculated as the change from fasting concentration. Fasting ghrelin and ghrelin AUC were higher among EA at baseline and week 8 (p < 0.001), and these differences were not affected by diet habituation. Despite greater postprandial ghrelin suppression, EA displayed greater hunger immediately following the test meal (p < 0.05). Overweight EA displayed higher circulating ghrelin and greater ghrelin suppression compared to AA. Further study is warranted to explore the physiological basis for these ethnic differences and to determine whether they may relate to higher obesity rates among AA.
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Low-glycemic load decreases postprandial insulin and glucose and increases postprandial ghrelin in white but not black women.
Brownley, KA, Heymen, S, Hinderliter, AL, Galanko, J, Macintosh, B
The Journal of nutrition. 2012;(7):1240-5
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Abstract
Alterations in appetite hormones favoring increased postprandial satiety have been implicated in both the glycemic control and potential weight-loss benefits of a low-glycemic diet. Racial differences exist in dietary glycemic load and appetite hormone concentrations. This study examined the impact of glycemic load on appetite hormones in 20 black women [10 normal weight, BMI = 22.8 ± 1.42 (mean ± SD); 10 obese, BMI = 35.1 ± 2.77] and 20 white women (10 normal weight, BMI = 22.9 ± 1.45; 10 obese, BMI = 34.3 ± 2.77). Each woman completed two 4.5-d weight-maintenance, mixed-macronutrient, high-glycemic vs. low-glycemic load diets that concluded with a test meal of identical composition. Blood samples collected before and serially for 3 h after each test meal were assayed for plasma ghrelin and serum insulin and glucose concentrations. Compared with the high-glycemic load meal, the low-glycemic load meal was associated with lower insulin(AUC) (P = 0.02), glucose(AUC) (P = 0.01), and urge to eat ratings (P = 0.05) but with higher ghrelin(AUC) (P = 0.008). These results suggest the satiating effect of a low-glycemic load meal is not directly linked to enhanced postprandial suppression of ghrelin. Notably, these effects were significant among white but not black women, suggesting that black women may be less sensitive than white women to the glucoregulatory effects of a low-glycemic load. These findings add to a growing literature demonstrating racial differences in postprandial appetite hormone responses. If reproducible, these findings have implications for individualized diet prescription for the purposes of glucose or weight control in women.
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Increase in energy intake leads to a decrease in obestatin in restricting-type of anorexia nervosa.
Uehara, M, Yasuhara, D, Nakahara, T, Harada, T, Koyama, KI, Ushikai, M, Asakawa, A, Inui, A
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2011;(9):536-9
Abstract
Restricting-type of anorexia nervosa (AN-R) is a serious disorder affecting adolescents and young adults, and decreases quality of life over long period. Successful weight restoration is an important prognostic factor for disease outcome; however, the underlying mechanism of refeeding-resistance, a core psychopathology relevant to 'ambivalent' eating behaviors, remains unclear in this disorder. Obestatin plays an important role in the regulation of growth hormone release, appetite, and energy metabolism. However, the progress of these patients and changes in the levels of obestatin during treatment were not reported. The purpose of this study was to determine the changes in obestatin levels when energy intake increases in AN-R patients. As a result, obestatin was higher in AN-R patients than in control subjects as well as acyl ghrelin and des-acyl ghrelin. An increase in the intake calorie has decreased obestatin as well as des-acyl ghrelin. These findings indicate that the obestatin is an important factor in the diagnosis and treatment of AN-R, similarly to acyl ghrelin and des-acyl ghrelin. In the future, the research on the clinical application of the ghrelin peptide family and the receptor will be expected to progress.