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1.
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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Regulation of iron homeostasis through the erythroferrone-hepcidin axis in sickle cell disease.
Mangaonkar, AA, Thawer, F, Son, J, Ajebo, G, Xu, H, Barrett, NJ, Wells, LG, Bowman, L, Clair, B, Patel, N, et al
British journal of haematology. 2020;(6):1204-1209
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Abstract
Sickle cell disease (SCD) has a distinct pattern of transfusional iron overload (IO) when compared to transfusion-dependent β-thalassaemia major (TDT). We conducted a single institution prospective study to evaluate plasma biomarkers of iron regulation and inflammation in patients with SCD with IO (SCD IO cases, n = 22) and without IO (SCD non-IO cases, n = 11), and non-SCD controls (n = 13). Hepcidin was found to be inappropriately low, as evidenced by a significantly higher median hepcidin/ferritin ratio in non-SCD controls compared to SCD IO cases (0·3 vs. 0·02, P < 0·0001) and SCD non-IO cases (0·3 vs. 0·02, P < 0·0001), suggesting that certain inhibitory mechanism (s) work to suppress hepcidin in SCD. As opposed to the SCD non-IO state, where hepcidin shows a strong significant positive correlation with ferritin (Spearman ρ = 0·7, P = 0·02), this correlation was lost when IO occurs (Spearman ρ = -0·2, P = 0·4). Although a direct non-linear correlation between erythroferrone (ERFE) and hepcidin did not reach statistical significance both in the IO (Spearman ρ = -0·4, P = 0·08) and non-IO state (Spearman ρ = -0·6, P = 0·07), patients with highest ERFE had low hepcidin levels, suggesting that ERFE contributes to hepcidin regulation in some patients. Our results suggest a multifactorial mechanism of hepcidin regulation in SCD.
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Changes in the Serum Hepcidin-to-ferritin Ratio with Erythroferrone after Hepatitis C Virus Eradication Using Direct-acting Antiviral Agents.
Inomata, S, Anan, A, Yamauchi, E, Yamauchi, R, Kunimoto, H, Takata, K, Tanaka, T, Yokoyama, K, Morihara, D, Takeyama, Y, et al
Internal medicine (Tokyo, Japan). 2019;(20):2915-2922
Abstract
Objective Hepcidin is a master iron regulator hormone produced by the liver, but precise mechanism underlying its involvement in iron overload in hepatitis C virus (HCV) infection remains unclear. We investigated the serum hepcidin levels against iron overload before and after HCV eradication. Methods We prospectively investigated the iron metabolism characteristics in 24 patients with HCV genotype 1b infection before and after treatment. We also assessed the serum erythroferrone (ERFE) levels to investigate its association with iron metabolism changes. Patients were treated with Ledipasvir 90 mg and Sofosbuvir 400 mg once daily for 12 weeks and observed for 12 more weeks in order to evaluate their sustained virological response. Results Serum hepcidin levels at baseline were in the normal range, although serum ferritin levels were increased. After HCV eradication, both serum ferritin and hepcidin levels were significantly decreased at 24 weeks from baseline (p<0.001, p=0.006, respectively). However, the serum hepcidin-to-ferritin ratios were significantly increased (p<0.001). In addition, the serum ERFE levels were significantly decreased (p<0.001). Increases in the serum hepcidin-to-ferritin ratios were correlated with decreases in the serum ERFE levels (ρ=-0.422, p=0.039). Conclusion Serum hepcidin levels were relatively low against ferritin levels in HCV infection. However, after HCV eradication, the serum hepcidin-to-ferritin ratios were increased. These results indicate the improvement of inadequate hepcidin secretion against iron overload after HCV eradication. Downregulation of ERFE may have affected the improvement of iron metabolism.
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Markers of metabolic health in children differ between weekdays--the result of unhealthier weekend behavior.
Hjorth, MF, Damsgaard, CT, Michaelsen, KF, Astrup, A, Sjödin, A
Obesity (Silver Spring, Md.). 2015;(4):733-6
Abstract
OBJECTIVE The aim of this study was to investigate whether indicators of metabolic health fluctuate during the week in a group of children posing unhealthier physical activity, sedentary time, and sleep during weekends compared to weekdays. METHODS A total of 807 eight- to eleven-year-old children had valid metabolic health markers from one, two, or three measurements contributing 2190 to 2240 observations of metabolic health markers. The weekly variation was tested using linear mixed models. RESULTS Homeostatic model assessment of insulin resistance (HOMAIR), triglycerides, leptin (all P < 0.001), and adiponectin (P = 0.03) decreased from Monday to Friday, whereas ghrelin increased (P < 0.001). HOMAIR , triglycerides, and leptin were 35%, 28%, and 33% higher on Mondays compared to Fridays, respectively, and ghrelin was 7% lower on Mondays compared to Fridays (all P < 0.001). CONCLUSIONS The large weekly variation in HOMAIR , triglycerides, and leptin was likely the result of unhealthier behaviors during weekends. These findings have public health relevance and raise methodological issues that should ideally be taken into account in future studies.
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The release of GLP-1 and ghrelin, but not GIP and CCK, by glucose is dependent upon the length of small intestine exposed.
Little, TJ, Doran, S, Meyer, JH, Smout, AJ, O'Donovan, DG, Wu, KL, Jones, KL, Wishart, J, Rayner, CK, Horowitz, M, et al
American journal of physiology. Endocrinology and metabolism. 2006;(3):E647-55
Abstract
Previous observations suggest that glucagon-like peptide-1 (GLP-1) is released into the bloodstream only when dietary carbohydrate enters the duodenum at rates that exceed the absorptive capacity of the proximal small intestine to contact GLP-1 bearing mucosa in more distal bowel. The aims of this study were to determine the effects of modifying the length of small intestine exposed to glucose on plasma concentrations of GLP-1 and also glucose-dependent insulinotropic peptide (GIP), insulin, cholecystokinin (CCK) and ghrelin, and antropyloric pressures. Glucose was infused at 3.5 kcal/min into the duodenum of eight healthy males (age 18-59 yr) over 60 min on the first day into an isolated 60-cm segment of the proximal small intestine ("short-segment infusion"); on the second day, the same amount of glucose was infused with access to the entire small intestine ("long-segment infusion"). Plasma GLP-1 increased and ghrelin decreased (P < 0.05 for both) during the long-, but not the short-, segment infusion. By contrast, increases in plasma CCK and GIP did not differ between days. The rises in blood glucose and plasma insulin were greater during the long- than during the short-segment infusion (P < 0.05). During the long- but not the short-segment infusion, antral pressure waves (PWs) were suppressed (P < 0.05). Isolated pyloric PWs and basal pyloric pressure were stimulated on both days. In conclusion, the release of GLP-1 and ghrelin, but not CCK and GIP, is dependent upon >60 cm of the intestine being exposed to glucose.
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Preprandial ghrelin is not affected by macronutrient intake, energy intake or energy expenditure.
Paul, DR, Kramer, M, Rhodes, DG, Rumpler, WV
Journal of negative results in biomedicine. 2005;:2
Abstract
BACKGROUND Ghrelin, a peptide secreted by endocrine cells in the gastrointestinal tract, is a hormone purported to have a significant effect on food intake and energy balance in humans. The influence of factors related to energy balance on ghrelin, such as daily energy expenditure, energy intake, and macronutrient intake, have not been reported. Secondly, the effect of ghrelin on food intake has not been quantified under free-living conditions over a prolonged period of time. To investigate these effects, 12 men were provided with an ad libitum cafeteria-style diet for 16 weeks. The macronutrient composition of the diets were covertly modified with drinks containing 2.1 MJ of predominantly carbohydrate (Hi-CHO), protein (Hi-PRO), or fat (Hi-FAT). Total energy expenditure was measured for seven days on two separate occasions (doubly labeled water and physical activity logs). RESULTS Preprandial ghrelin concentrations were not affected by macronutrient intake, energy expenditure or energy intake (all P > 0.05). In turn, daily energy intake was significantly influenced by energy expenditure, but not ghrelin. CONCLUSION Preprandial ghrelin does not appear to be influenced by macronutrient composition, energy intake, or energy expenditure. Similarly, ghrelin does not appear to affect acute or chronic energy intake under free-living conditions.
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Effect of moderate incremental exercise, performed in fed and fasted state on cardio-respiratory variables and leptin and ghrelin concentrations in young healthy men.
Zoladz, JA, Konturek, SJ, Duda, K, Majerczak, J, Sliwowski, Z, Grandys, M, Bielanski, W
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 2005;(1):63-85
Abstract
BACKGROUND Although hormonal responses to exercise performed in fed state are well documented, far less in known about the effect of a single exercise bout, performed after overnight fasting, on cardio-respiratory responses and hormones secretion. It has been reported that recently discovered hormones as leptin and ghrelin may affect cardiovascular responses at rest. However, their effect on the cardiovascular responses to exercise is unknown. AIMS This study was designed to determine the effect of overnight fasting on cardio- respiratory responses during moderate incremental exercise. We have hypothesised that fasting / exercise induced changes in plasma leptin / ghrelin concentrations may influence cardiovascular response. MATERIAL AND METHODS Eight healthy non-smoking men (means +/- SE.: age 23.0 +/- 0.5 years; body mass 71.9 +/- 1.5 kg; height 179.1 +/- 0.8 cm; BMI 22.42 +/- 0.49 kg x m(-2) with VO2max of 3.71 +/- 0.10 l x min(-1)) volunteered for this study. The subjects performed twice an incremental exercise test, with the increase of power output by 30 W every 3 minutes. Tests were performed in a random order: once in the feed state--cycling until exhaustion and second, about one week later, after overnight fasting--cycling until reaching 150 W. RESULTS In the present study we have compared the results obtained during incremental exercise performed only up to 150 W (59 +/- 2 % of VO2max) both in fed and fasted state. Heart rate measured during exercise at each power output, performed in fasted state was by about 10 bt x min(-1) (p = 0.02) lower then in fed subjects. Respiratory quotient and plasma lactate concentration in fasted state were also significantly (p<0.001) lower than in the fed state. Pre-exercise plasma leptin and ghrelin concentrations were not significantly different in fed and fasted state. Exercise induced increase in hGH was not accompanied by a significant changes in the studied gut hormones such as ghrelin, leptin, and insulin, except for plasma gastrin concentration, which was significantly (p = 0.008) lower in fasting subjects at the power output of 150 W. Plasma [IL-6] at rest before exercise performed in fasted state was significantly (p = 0.03) elevated in relation to the fed state. This was accompanied by significantly higher (p = 0.047) plasma noradrenaline concentration. Plasma IL-6 concentration at rest in fed subjects was negatively correlated with plasma ghrelin concentration (r = -0.73, p < 0.05) and positively correlated with plasma insulin concentration (r = 0.78, p < 0.05). Significant negative correlation (r = -0.90; p < 0.05) was found between plasma insulin and ghrelin concentration at rest in fed subjects. CONCLUSIONS We have concluded that plasma leptin and ghrelin concentrations have no significant effect on the fasting-induced attenuation of heart rate during exercise. We have postulated that this effect is caused by increased plasma norepinephrine concentration, leading to the increase in systemic vascular resistance and baroreceptor mediated vagal stimulation. Moreover we believe, that the fasting-induced significant increase in plasma IL-6 concentration at rest, accompanied by higher plasma norepinephrine concentration and lower RQ, belongs to the physiological responses, maintaining energy homeostasis in the fasting state.
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Ghrelin response to carbohydrate-enriched breakfast is related to insulin.
Blom, WA, Stafleu, A, de Graaf, C, Kok, FJ, Schaafsma, G, Hendriks, HF
The American journal of clinical nutrition. 2005;(2):367-75
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Abstract
BACKGROUND Ghrelin plays an important role in the regulation of food intake. Little is known about how ghrelin concentrations are modified by dietary factors. OBJECTIVE We examined the effects of both amount and type of carbohydrate on ghrelin concentrations and all correlations among the variables ghrelin, glucose, insulin, leptin, and all 4 subjective measures of appetite. DESIGN Twenty healthy nonobese men were studied in a double-blind, randomized, crossover design. Subjective measures of appetite and concentrations of ghrelin, glucose, insulin, and leptin were frequently assessed for 4 h after liquid breakfast meals differing in energy content and carbohydrate structure-ie, water, low-calorie (LC) meal, high-calorie simple carbohydrate (HC-SC) meal, and high-calorie complex carbohydrate (HC-CC) meal. RESULTS Ghrelin concentrations decreased after the HC-SC breakfast by 41%, after the HC-CC breakfast by 33%, and after the LC breakfast by 24%. No significant differences in ghrelin concentration among the 3 breakfasts were observed until 120 min. Ghrelin concentrations were correlated with subjective measures of hunger (r=0.51) and fullness (r=-0.44). The percentage decrease in ghrelin between 0 and 30 min was inversely correlated with the percentage increases in insulin (r=-0.76) and glucose (r=-0.79) but not with changes in leptin (r=0.10). The percentage changes in ghrelin concentrations between 30 and 180 min were correlated with the percentage changes in insulin (r=-0.53) and leptin (r=-0.47) but not with changes in glucose (r=0.22). CONCLUSION The results support the hypothesis that ghrelin requires postgastric feedback, which may be regulated through insulin.
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Metabolic regulation of growth hormone by free fatty acids, somatostatin, and ghrelin in HIV-lipodystrophy.
Koutkia, P, Meininger, G, Canavan, B, Breu, J, Grinspoon, S
American journal of physiology. Endocrinology and metabolism. 2004;(2):E296-303
Abstract
Human immunodeficiency virus (HIV)-lipodystrophy is a syndrome characterized by changes in fat distribution and insulin resistance. Prior studies suggest markedly reduced growth hormone (GH) levels in association with excess visceral adiposity among patients with HIV-lipodystrophy. We investigated mechanisms of altered GH secretion in a population of 13 male HIV-infected patients with evidence of fat redistribution, compared with 10 HIV-nonlipodystrophic patients and 11 male healthy controls similar in age and body mass index (BMI). Although similar in BMI, the lipodystrophic group was characterized by increased visceral adiposity, free fatty acids (FFA), and insulin and reduced extremity fat. We investigated ghrelin and the effects of acute lowering of FFA by acipimox on GH responses to growth hormone-releasing hormone (GHRH). We also investigated somatostatin tone, comparing GH response to combined GHRH and arginine vs. GHRH alone with a subtraction algorithm. Our data demonstrate an equivalent number of GH pulses (4.1 +/- 0.6, 4.7 +/- 0.8, and 4.5 +/- 0.3 pulses/12 h in the HIV-lipodystrophic, HIV-nonlipodystrophic, and healthy control groups, respectively, P > 0.05) but markedly reduced GH secretion pulse area (1.14 +/- 0.27 vs. 4.67 +/- 1.24 ng.ml(-1).min, P < 0.05, HIV-lipodystrophic vs. HIV-nonlipodystrophic; 1.14 +/- 0.27 vs. 3.18 +/- 0.92 ng.ml(-1).min, P < 0.05 HIV-lipodystrophic vs. control), GH pulse area, and GH pulse width in the HIV-lipodystrophy patients compared with the control groups. Reduced ghrelin (418 +/- 46 vs. 514 +/- 37 pg/ml, P < 0.05, HIV-lipodystrophic vs. HIV-nonlipodystrophic; 418 +/- 46 vs. 546 +/- 45 pg/ml, P < 0.05, HIV-lipodystrophic vs. control), impaired GH response to GHRH by excess FFA, and increased somatostatin tone contribute to reduced GH secretion in patients with HIV-lipodystrophy. These data provide novel insight into the metabolic regulation of GH secretion in subjects with HIV-lipodystrophy.
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Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues.
Cummings, DE, Frayo, RS, Marmonier, C, Aubert, R, Chapelot, D
American journal of physiology. Endocrinology and metabolism. 2004;(2):E297-304
Abstract
Ghrelin is an orexigenic hormone that is implicated in meal initiation, in part because circulating levels rise before meals. Because previous human studies have examined subjects fed on known schedules, the observed preprandial ghrelin increases could have been a secondary consequence of meal anticipation. A causal role for ghrelin in meal initiation would be better supported if preprandial increases occurred before spontaneously initiated meals not prompted by external cues. We measured plasma ghrelin levels among human subjects initiating meals voluntarily without cues related to time or food. Samples were drawn every 5 min between a scheduled lunch and a freely requested dinner, and hunger scores were obtained using visual analog scales. Insulin, glucose, fatty acids, leptin, and triglycerides were also measured. Ghrelin levels decreased shortly after the first meal in all subjects. A subsequent preprandial increase occurred over a wide range of intermeal intervals (IMI; 320-425 min) in all but one subject. Hunger scores and ghrelin levels showed similar temporal profiles and similar relative differences in magnitude between lunch and dinner. One subject displayed no preprandial ghrelin increase and was also the only individual whose insulin levels did not return to baseline between meals. This finding, along with a correlation between area-under-the-curve values of ghrelin and insulin, suggests a role for insulin in ghrelin regulation. The preprandial increase of ghrelin levels that we observed among humans initiating meals voluntarily, without time- or food-related cues, and the overlap between these levels and hunger scores are consistent with a role for ghrelin in meal initiation.