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Probiotics have minimal effects on appetite-related hormones in overweight or obese individuals: A systematic review of randomized controlled trials.
Cabral, LQT, Ximenez, JA, Moreno, KGT, Fernandes, R
Clinical nutrition (Edinburgh, Scotland). 2021;(4):1776-1787
Abstract
BACKGROUND & AIMS Overweight and obese individuals show changes in mechanisms related to appetite due to several factors, including excess fat and gut microbiota imbalance. Probiotics have been presented as a strategy for modulating gut microbiota and regulating these mechanisms. The aim of this systematic review was to assess the effects of probiotics on appetite-related hormones in overweight or obese individuals. METHODS A systematic review of randomized controlled trials was performed in nine electronic databases (Pubmed, Scopus, Web of Science, Cochrane Controlled Register of Trials, ProQuest Dissertations and Theses, PsycINFO, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov and Open Grey) and in a manual search of studies until March 20, 2020. The risk of bias of each study was appraised using the RoB 2.0 tool. All research stages were carefully based on PRISMA recommendations. RESULTS Twenty-four studies (1587 participants) were included in this systematic review. The outcomes related to appetite assessed in the included studies were: leptin, insulin, adiponectin, resistin, nesfatin-1, adropin, omentin-1, GLP-1, GLP-2 and glucagon. Compared to the control group after supplementation, four studies involving 272 participants reported statistically significant reduction in fasting insulin. On the other hand, one study involving 56 participants reported statistically significant increase in adropin and omentin-1. CONCLUSIONS Probiotics have minimal effects on appetite-related hormones in overweight or obese individuals. However, knowledge in this area is progressing and further studies with a low risk of bias may help to clarify the role of probiotics in appetite control.
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2.
The Role of Iron in Benign and Malignant Hematopoiesis.
Sinha, S, Pereira-Reis, J, Guerra, A, Rivella, S, Duarte, D
Antioxidants & redox signaling. 2021;(6):415-432
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Abstract
Significance: Iron is an essential element required for sustaining a normal healthy life. However, an excess amount of iron in the bloodstream and tissue generates toxic hydroxyl radicals through Fenton reactions. Henceforth, a balance in iron concentration is extremely important to maintain cellular homeostasis in both normal hematopoiesis and erythropoiesis. Iron deficiency or iron overload can impact hematopoiesis and is associated with many hematological diseases. Recent Advances: The mechanisms of action of key iron regulators such as erythroferrone and the discovery of new drugs, such as ACE-536/luspatercept, are of potential interest to treat hematological disorders, such as β-thalassemia. New therapies targeting inflammation-induced ineffective erythropoiesis are also in progress. Furthermore, emerging evidences support differential interactions between iron and its cellular antioxidant responses of hematopoietic and neighboring stromal cells. Both iron and its systemic regulator, such as hepcidin, play a significant role in regulating erythropoiesis. Critical Issues: Significant pre-clinical studies are on the way and new drugs targeting iron metabolism have been recently approved or are undergoing clinical trials to treat pathological conditions with impaired erythropoiesis such as myelodysplastic syndromes or β-thalassemia. Future Directions: Future studies should explore how iron regulates hematopoiesis in both benign and malignant conditions. Antioxid. Redox Signal. 35, 415-432.
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The role of Elabela in kidney disease.
Zheng, Q, Tian, G, Xu, F, Ci, X, Luan, R, Wu, L, Lu, X
International urology and nephrology. 2021;(9):1851-1857
Abstract
Elabela, also known as Toddler or Apela, is a recently discovered hormonal peptide containing 32 amino acids. Elabela is a ligand of the apelin receptor (APJ). APJ is a G protein-coupled receptor widely expressed throughout body, and together with its cognate ligand, apelin, it plays an important role in various physiological processes including cardiovascular functions, angiogenesis and fluid homeostasis. Elabela also participates in embryonic development and pathophysiological processes in adulthood. Elabela is highly expressed in undifferentiated embryonic stem cells and regulates endoderm differentiation and cardiovascular system development. During differentiation, Elabela is highly expressed in pluripotent stem cells and in adult renal collecting ducts and loops, where it functions to maintain water and sodium homeostasis. Other studies have also shown that Elabela plays a crucial role in the pathogenesis of kidney diseases. This review addresses the role of Elabela in kidney diseases including renal ischemia/reperfusion injury, hypertensive nephropathy, diabetic nephropathy, and cardiorenal syndrome.
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ANGPTL8 in metabolic homeostasis: more friend than foe?
Guo, C, Wang, C, Deng, X, He, J, Yang, L, Yuan, G
Open biology. 2021;(9):210106
Abstract
ANGPTL8 is an important cytokine, which is significantly increased in type 2 diabetes mellitus (T2DM), obesity and metabolic syndrome. Many studies have shown that ANGPTL8 can be used as a bio-marker of these metabolic disorders related diseases, and the baseline ANGPTL8 level has also been found to be positively correlated with retinopathy and all-cause mortality in patients with T2DM. This may be related to the inhibition of lipoprotein lipase activity and the reduction of circulating triglyceride (TG) clearance by ANGPTL8. Consistently, inhibition of ANGPTL8 seems to prevent or improve atherosclerosis. However, it is puzzling that ANGPTL8 seems to have a directing function for TG uptake in peripheral tissues; that is, ANGPTL8 specifically enhances the reserve and buffering function of white adipose tissue, which may alleviate the ectopic lipid accumulation to a certain extent. Furthermore, ANGPTL8 can improve insulin sensitivity and inhibit hepatic glucose production. These contradictory results lead to different opinions on the role of ANGPTL8 in metabolic disorders. In this paper, the correlation between ANGPTL8 and metabolic diseases, the regulation of ANGPTL8 and the physiological role of ANGPTL8 in the process of glucose and lipid metabolism were summarized, and the physiological/pathological significance of ANGPTL8 in the process of metabolic disorder was discussed.
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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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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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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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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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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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Erythroferrone, the new iron regulator: evaluation of its levels in Egyptian patients with beta thalassemia.
El-Gamal, RAE, Abdel-Messih, IY, Habashy, DM, Zaiema, SEG, Pessar, SA
Annals of hematology. 2020;(1):31-39
Abstract
Since iron overload is the commonest cause of morbidity and mortality in β thalassemia major (β-TM), it represents one major target in therapeutic management of the disease. The recently discovered erythroid regulator, erythroferrone (ERFE), governed by high levels of erythropoietin, was found to suppress hepcidin expression, thus increasing iron availability for developing erythroid progenitors. We aimed to investigate ERFE levels in Egyptian β-TM patients as an attempt to understand its role in the prediction of iron overload states. Our study included 70 β-TM patients, divided into two subgroups according to the degree of iron overload, and 30 sex and age-matched healthy subjects. ERFE gene expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), and serum hepcidin was measured using enzyme-linked immunosorbent assay (ELISA) technique. Both ERFE gene expression levels and transferrin saturation (TS%) values were able to discriminate among cases with different degrees of iron overload, in contrast to hepcidin. TS% was acknowledged as the best predictor of iron overload (AUC 0.893) in comparison with serum hepcidin and ERFE gene levels (AUC 0.807 and 0.677, respectively), and ERFE gene expression was an independent predictor for the estimated TS%. In conclusion, we suggest that using the ERFE gene expression, combined with serum hepcidin estimation, can substantiate the role of estimated TS% as a promising tool in screening for iron overload in β-TM patients.