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Alogaiel DM, Alsuwaylihi A, Alotaibi MS, Macdonald IA, Lobo DN. Effects of Ramadan intermittent fasting on hormones regulating appetite in healthy individuals: A systematic review and meta-analysis. Clin Nutr 2025; 45:250-261. [PMID: 39842253 DOI: 10.1016/j.clnu.2025.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 12/17/2024] [Accepted: 01/05/2025] [Indexed: 01/24/2025]
Abstract
BACKGROUND AND AIMS This systematic review and meta-analysis aimed to examine the effect of Ramadan intermittent fasting on appetite-regulating hormones including leptin, ghrelin, insulin, gastrin, glucagon-like peptide-1, peptide YY, and cholecystokinin. METHODS We searched the MEDLINE, Embase, Cochrane Library, CINAHL, Google Scholar, and Web of Science databases to identify relevant research on appetite-regulating hormones during Ramadan intermittent fasting, published until the end of March 2024. RESULTS Data from 16 eligible studies comprising 664 participants (341, 51.4 % male) with a mean ± standard deviation age of 33.9 ± 10.8 years were included. The meta-analysis included 12 studies with complete leptin data, showing no significant effect of Ramadan intermittent fasting on leptin concentrations (standardised mean difference - SMD = -0.11 μg/mL, 95 % CI: -0.36 to 0.14). Analysis of three studies with complete ghrelin data demonstrated a significant increase in ghrelin concentrations following Ramadan intermittent fasting (SMD = 0.31 pg/mL, 95 % CI: 0.03 to 0.60). Six studies examining insulin concentrations pre- and post-fasting revealed no significant effect on insulin concentrations (SMD = -0.24 μU/mL, 95 % CI: -0.54 to 0.02). Similarly, analysis of three studies with complete gastrin data showed no significant effect of intermittent fasting on gastrin concentrations (SMD = 0.23 pg/mL, 95 % CI: -0.71 to 0.99). CONCLUSION Ramadan intermittent fasting significantly increases ghrelin concentrations while showing no significant effects on leptin, insulin, and gastrin. While ghrelin findings were consistent across studies, the high heterogeneity in leptin studies suggests further research to better understand the effects of Ramadan intermittent fasting on appetite-regulating hormones.
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Affiliation(s)
- Deema M Alogaiel
- Nottingham Digestive Diseases Centre, Division of Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK; National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham, UK; MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK; Health Sciences Department, College of Health and Rehabilitation, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Abdulaziz Alsuwaylihi
- Nottingham Digestive Diseases Centre, Division of Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK; National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham, UK; Department of Clinical Nutrition, King Saud Medical City, Ministry of Health, Riyadh, Saudi Arabia
| | - May S Alotaibi
- Health Sciences Department, College of Health and Rehabilitation, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; Division of Food, Nutrition & Dietetics, School of Biosciences, University of Nottingham, LE12 5RD, UK
| | - Ian A Macdonald
- National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham, UK; MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK
| | - Dileep N Lobo
- Nottingham Digestive Diseases Centre, Division of Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK; National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham, UK; MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK; Division of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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Sadighi A, Aghamohammadpour Z, Sadeghpour Heravi F, Somi MH, Masnadi Shirazi Nezhad K, Hosseini S, Bahman Soufiani K, Ebrahimzadeh Leylabadlo H. The protective effects of Helicobacter pylori: A comprehensive review. JOURNAL OF RESEARCH IN CLINICAL MEDICINE 2024; 12:17. [DOI: 10.34172/jrcm.34509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 10/15/2023] [Indexed: 01/03/2025] Open
Abstract
Previous reports have estimated that approximately half of the world’s population is infected with Helicobacter pylori, the most prevalent infectious agent responsible for gastrointestinal illnesses. Due to the life-threatening effects of H. pylori infections, numerous studies have focused on developing medical therapies for H. pylori infections, while the commensal relationship and positive impacts of this bacterium on overall human health have been largely overlooked. The inhibitory efficacy of H. pylori on the progression of several chronic inflammatory disorders and gastrointestinal diseases has recently raised concerns about whether this bacterium should be eradicated in affected individuals or maintained in an appropriate balance depending on the patient’s condition. This review investigates the beneficial effects of H. pylori in preventing various diseases and discusses the potential association of conditions such as inflammatory disorders with the absence of H. pylori.
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Affiliation(s)
- Ali Sadighi
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zahra Aghamohammadpour
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Mohammad Hossein Somi
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Samaneh Hosseini
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Katayoun Bahman Soufiani
- Department of Laboratory Sciences and Microbiology, Faculty of Medical Sciences, Tabriz Medical Sciences, Islamic Azad University, Tabriz, Iran
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Lam CSD, Kaelberer MM. The pressure not to eat. Nat Metab 2024; 6:380-381. [PMID: 38467888 DOI: 10.1038/s42255-024-01002-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/13/2024]
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Yao R, Cools A, van Hees HMJ, Chiers K, Mebratu AT, Aluwé M, Maes D, Janssens GPJ. Getting clues from nature: the impact of grass hay on suckling piglets' gastrointestinal growth and colonic microbiota. Front Cell Infect Microbiol 2024; 13:1341147. [PMID: 38268791 PMCID: PMC10806113 DOI: 10.3389/fcimb.2023.1341147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Accepted: 12/15/2023] [Indexed: 01/26/2024] Open
Abstract
Introduction The effect of dietary fiber on pig production has been extensively evaluated. Inspired by observations of the diet of wild, young piglets, this study aimed to examine the possibility of feeding grass hay to suckling piglets besides concentrated creep feed. Methods The sow-nursed piglets in this study were divided into two groups based on balanced sow parities. The control group (CON, n = 7 sows) only received a regular, concentrated creep feed, while the treatment piglets (GH, n = 8 sows) were also provided with chopped grass hay from 2 days of age until weaning (28 days). At weaning, one piglet with a median weight was selected from each litter for post-mortem evaluation. Subsequently, six pigs around median weight per sow were grouped into nursery pens and monitored for their feed intake and body weight gain until 9 weeks of age. Results and discussion Piglets in GH consumed, on average, 57 g of grass hay per piglet during the entire lactation period. The emptied weight of the small and large intestine was significantly greater in GH (280 vs. 228 g, 88.8 vs. 79.3 g, respectively, p < 0.05), and the length of the large intestine was stimulated by the grass hay (164 vs. 150 cm, p < 0.05). Morphologically, the villus height in the jejunum was higher in GH (p < 0.05). In the large intestine, the crypt depth of the mid-colon was lower in GH. Moreover, the short-chain fatty acid (SCFA) concentrations in the cecum were increased in GH compared to CON (1,179 vs. 948 µmol/g dry matter, p < 0.05), whereas in the colon, SCFA concentrations were lower in CON (341 vs. 278 µmol/g dry matter, p < 0.05). There was no major impact of grass hay inclusion on the colonic microbiota composition. Only a trend was observed for a lower inverse of the classical Simpson (InvSimpon) index and a higher abundance of Lactobacillus genera in GH. After weaning, no significant differences in feed intake and body weight gain were observed. In conclusion, supplementing the grass hay to suckling piglets led to alterations in intestinal morphology, increased SCFA fermentation in proximal sections of large intestine, stimulation of gastrointestinal tract growth, and subtle modifications in colonic microbiota.
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Affiliation(s)
- Renjie Yao
- Department of Veterinary and Biosciences, Ghent University, Merelbeke, Belgium
- Department of Internal Medicine, Reproduction and Population Medicine, Ghent University, Merelbeke, Belgium
| | - An Cools
- Department of Veterinary and Biosciences, Ghent University, Merelbeke, Belgium
| | - Hubèrt M. J. van Hees
- Department of Veterinary and Biosciences, Ghent University, Merelbeke, Belgium
- Trouw Nutrition Research & Development, Amersfoort, Netherlands
| | - Koen Chiers
- Department of Pathology, Ghent University, Merelbeke, Belgium
| | - Awot Teklu Mebratu
- Department of Veterinary and Biosciences, Ghent University, Merelbeke, Belgium
| | - Marijke Aluwé
- Flanders Research Institute for Agriculture, Fisheries and Food (ILVO), Melle, Belgium
| | - Dominiek Maes
- Department of Internal Medicine, Reproduction and Population Medicine, Ghent University, Merelbeke, Belgium
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Pati B, Sendh S, Sahu B, Pani S, Jena N, Bal NC. Recent advancements in pharmacological strategies to modulate energy balance for combating obesity. RSC Med Chem 2023; 14:1429-1445. [PMID: 37593583 PMCID: PMC10429841 DOI: 10.1039/d3md00107e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 06/06/2023] [Indexed: 08/19/2023] Open
Abstract
The prevalence of obesity along with its related metabolic diseases has increased globally in recent decades. Obesity originates from a heterogeneous physiological state, which is further complicated by the influence of factors such as genetic, behavioural, and environmental. Lifestyle interventions including exercise and diet have limited success, necessitating the development of pharmacological approaches. Mechanistically, strategies target either reducing energy intake or increasing consumption through metabolism boosting. Current drugs lower energy intake via inducing satiety or inhibiting substrate absorption, while targeting mitochondria or cytosolic energy sensors has shown limited success due to toxicity. Nonshivering thermogenesis (NST) has provided hope for activating these processes selectively without significant side effects. The internet-based marketing of plant-based formulations for enhancing metabolism has surged. This review compiles scientific articles, magazines, newspapers, and online resources on anti-obesity drug development. Combination therapy of metabolic boosters and established anti-obesity compounds appears to be a promising future approach that requires further research.
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Affiliation(s)
- Benudhara Pati
- School of Biotechnology, KIIT University Bhubaneswar Odisha 751024 India
| | - Satyabrata Sendh
- School of Biotechnology, KIIT University Bhubaneswar Odisha 751024 India
| | - Bijayashree Sahu
- School of Biotechnology, KIIT University Bhubaneswar Odisha 751024 India
| | - Sunil Pani
- School of Biotechnology, KIIT University Bhubaneswar Odisha 751024 India
| | - Nivedita Jena
- Institute of Life Science, DBT ILS Bioincubator Bhubaneswar Odisha 751021-India
| | - Naresh Chandra Bal
- School of Biotechnology, KIIT University Bhubaneswar Odisha 751024 India
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Liu FS, Wang S, Guo XS, Ye ZX, Zhang HY, Li Z. State of art on the mechanisms of laparoscopic sleeve gastrectomy in treating type 2 diabetes mellitus. World J Diabetes 2023; 14:632-655. [PMID: 37383590 PMCID: PMC10294061 DOI: 10.4239/wjd.v14.i6.632] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 04/01/2023] [Accepted: 04/24/2023] [Indexed: 06/14/2023] Open
Abstract
Obesity and type-2 diabetes mellitus (T2DM) are metabolic disorders. Obesity increases the risk of T2DM, and as obesity is becoming increasingly common, more individuals suffer from T2DM, which poses a considerable burden on health systems. Traditionally, pharmaceutical therapy together with lifestyle changes is used to treat obesity and T2DM to decrease the incidence of comorbidities and all-cause mortality and to increase life expectancy. Bariatric surgery is increasingly replacing other forms of treatment of morbid obesity, especially in patients with refractory obesity, owing to its many benefits including good long-term outcomes and almost no weight regain. The bariatric surgery options have markedly changed recently, and laparoscopic sleeve gastrectomy (LSG) is gradually gaining popularity. LSG has become an effective and safe treatment for type-2 diabetes and morbid obesity, with a high cost-benefit ratio. Here, we review the me-chanism associated with LSG treatment of T2DM, and we discuss clinical studies and animal experiments with regard to gastrointestinal hormones, gut microbiota, bile acids, and adipokines to clarify current treatment modalities for patients with obesity and T2DM.
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Affiliation(s)
- Fa-Shun Liu
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
| | - Song Wang
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
| | - Xian-Shan Guo
- Department of Endocrinology, Xinxiang Central Hospital, Xinxiang 453000, Henan Province, China
| | - Zhen-Xiong Ye
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
| | - Hong-Ya Zhang
- Central Laboratory, Yangpu District Control and Prevention Center, Shanghai 200090, China
| | - Zhen Li
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
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Korkusuz M, Basaran B, Et T, Bilge A, Yarimoglu R, Osmanoglu UO. Gastric emptying times of obese and non-obese school-aged children after preoperative clear fluid intake: A prospective observational study. Paediatr Anaesth 2023. [PMID: 36876549 DOI: 10.1111/pan.14658] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 02/09/2023] [Accepted: 02/27/2023] [Indexed: 03/07/2023]
Abstract
BACKGROUND Liberal fasting regimens, which support clear fluid intake up to 1 h before surgery in children scheduled for elective surgery, are taking their place in guidelines. However, because of the lack of publications that investigate the gastric emptying time in preoperative obese children, the practice of 1-hour clear fluid fasting in obese children remained at the level of recommendation with weak evidence. AIMS The primary aim was to investigate whether there is a difference in gastric emptying times between obese and non- obese children after preoperative intake of 3 mL/kg clear liquid containing 5% dextrose by using ultrasound. METHODS A total of 70 children were included in the study in two groups, 35 obese and 35 non-obese, aged 6-14 years, who were scheduled for elective surgery. The baseline antral cross-sectional area measurements of the children in the groups were made using ultrasound. 3 mL/kg 5% dextrose was consumed. Ultrasound was repeated immediately after fluid intake and every 5 min until the antral cross-sectional area was at the baseline level. RESULTS The difference in median (IQR [range]) gastric emptying times (minutes) of non-obese {35 [30.0-45.0 (20-60)]} and obese children {35 [30.0-40.0 (25-60)]} were not statistically significant (median of differences 0.0, 95% CI -5.0 to 5.0; p = .563). The antral cross-sectional area and weight-adjusted gastric volumes returned to the baseline level within 60 min after the intake of clear liquid with 3 mL/kg 5% dextrose in all children in both groups. CONCLUSIONS Obese and non-obese children have similar gastric emptying times, and these groups can be offered clear fluids containing 3 mL/kg 5% dextrose 1 h before the surgery.
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Affiliation(s)
- Muhammet Korkusuz
- Department of Anaesthesiology and Reanimation, Karamanoglu Mehmetbey University, School of Medicine, Karaman, Turkey
| | - Betul Basaran
- Department of Anaesthesiology and Reanimation, Karamanoglu Mehmetbey University, School of Medicine, Karaman, Turkey
| | - Tayfun Et
- Department of Anaesthesiology and Reanimation, Karamanoglu Mehmetbey University, School of Medicine, Karaman, Turkey
| | - Aysegul Bilge
- Department of Anaesthesiology and Reanimation, Karamanoglu Mehmetbey University, School of Medicine, Karaman, Turkey
| | - Rafet Yarimoglu
- Department of Anaesthesiology and Reanimation, Karaman Training and Research Hospital, Karaman, Turkey
| | - Usame Omer Osmanoglu
- Department of Biostatistics, Karamanoglu Mehmetbey University, School of Medicine, Karaman, Turkey
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Kaneko K, Tokuyama Y, Taniguchi E, Abe S, Nakato J, Iwakura H, Sato M, Kurabayashi A, Suzuki H, Ito A, Higuchi Y, Nakayama R, Uchiyama K, Takahashi H, Ohinata K. Rice Endoplasmic Protein-Derived Peptides, Rice-Ghretropins A and B, Stimulate Ghrelin Release in MGN3-1 Cells and Increase Plasma Acylated Ghrelin and Food Intake in Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:421-429. [PMID: 36580688 DOI: 10.1021/acs.jafc.2c05965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
In this study, we demonstrated that novel rice-derived bioactive peptides promote the secretion of ghrelin, an endogenous orexigenic hormone secreted from the stomach. The enzymatic digest of rice endosperm protein with subtilisin, a microorganism-derived enzyme, stimulated acylated ghrelin secretion in the ghrelin-releasing cell line MGN3-1 and increased food intake after oral administration in mice. By performing a comprehensive analysis based on structure-activity relationships, we selected candidate peptides from over 30,000 peptides in the rice digest. Among them, we found that QAFEPIRSV and TNPWHSPRQGSF, corresponding to the amino acid sequence of the rice endoplasmic proteins glutelin A1 or A2(52-60) and B1 or B2(31-42), respectively, stimulated acylated ghrelin release in MGN3-1 cells. We named them rice-ghretropins A and B. Pyroglutamate formation of rice-ghretropin A, [pyr1]-rice-ghretropin A, also promoted ghrelin secretion. Furthermore, oral administration of rice-ghretropins increased food intake, plasma ghrelin concentration, and small intestinal transit in mice. In addition, the subtilisin digest of the rice protein significantly increased food intake for 4 h in 9 month-old (control: 0.61 ± 0.049 g; digest: 0.83 ± 0.059 g) and 24 month-old mice (control: 0.52 ± 0.067 g; digest: 1.01 ± 0.064 g). In summary, we found that novel bioactive peptides, namely, rice-ghretropins, from the enzymatic digest of rice endosperm stimulated acylated ghrelin secretion and increased food intake. This is the first report of rice-derived exogenous bioactive peptides that increase acylated ghrelin secretion.
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Affiliation(s)
- Kentaro Kaneko
- Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan
| | - Yuki Tokuyama
- Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan
| | - Eriko Taniguchi
- Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan
| | - Shimon Abe
- Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan
| | - Junya Nakato
- Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan
| | - Hiroshi Iwakura
- The First Department of Medicine, Wakayama Medical University, Wakayama 841-8509, Japan
| | - Masaru Sato
- Department of Applied Genomics, Kazusa DNA Research Institute, 2-6-7 Kazusakamatari, Kisarazu, Chiba 292-0818, Japan
| | - Atsushi Kurabayashi
- Department of Applied Genomics, Kazusa DNA Research Institute, 2-6-7 Kazusakamatari, Kisarazu, Chiba 292-0818, Japan
| | - Hideyuki Suzuki
- Department of Applied Genomics, Kazusa DNA Research Institute, 2-6-7 Kazusakamatari, Kisarazu, Chiba 292-0818, Japan
| | - Akira Ito
- Rice Research Institute, Kameda Seika CO., LTD. 3-1-1Kameda-kogyodanchi, Konan, Niigata, Niigata 950-0198, Japan
| | - Yuki Higuchi
- Rice Research Institute, Kameda Seika CO., LTD. 3-1-1Kameda-kogyodanchi, Konan, Niigata, Niigata 950-0198, Japan
| | - Ryoko Nakayama
- Rice Research Institute, Kameda Seika CO., LTD. 3-1-1Kameda-kogyodanchi, Konan, Niigata, Niigata 950-0198, Japan
| | - Kimiko Uchiyama
- Rice Research Institute, Kameda Seika CO., LTD. 3-1-1Kameda-kogyodanchi, Konan, Niigata, Niigata 950-0198, Japan
| | - Hajime Takahashi
- Rice Research Institute, Kameda Seika CO., LTD. 3-1-1Kameda-kogyodanchi, Konan, Niigata, Niigata 950-0198, Japan
| | - Kousaku Ohinata
- Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan
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Ramos AC, Bastos ELDS. Anatomical Considerations. DUODENAL SWITCH AND ITS DERIVATIVES IN BARIATRIC AND METABOLIC SURGERY 2023:219-228. [DOI: 10.1007/978-3-031-25828-2_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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De Mille CM, Burrough ER, Kerr BJ, Schweer WP, Gabler NK. Dietary Pharmacological Zinc and Copper Enhances Voluntary Feed Intake of Nursery Pigs. FRONTIERS IN ANIMAL SCIENCE 2022. [DOI: 10.3389/fanim.2022.874284] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
The objective of the three experiments herein were to characterize the effect of pharmacological zinc and copper concentrations on nursery pig feed intake, stomach ghrelin, energy and nutrient digestibility, and mineral retention in post-weaned pigs. In Expt. 1, 300 weaned pigs were allotted across three dietary treatments (n = 10 pens/treatment) and fed in two diet phases (P1 and P2) lasting 7 and 14 days, respectively. Treatments were: (1) Control diet with no pharmacological minerals in P1 and P2, CON; (2) CON + 3,000 mg/kg Zn and 200 mg/kg Cu (P1), no pharmacological minerals in P2, ZC-CON; and (3) CON + 3,000 mg/kg Zn and 200 mg/kg Cu (P1), CON + 2,000 mg/kg Zn and 200 mg/kg Cu (P2); ZC. Over the 21-day test period, ZC pigs had 15% higher ADG and 13–24% ADFI compared to the CON and ZC-CON pigs (P < 0.05). ZC-CON and ZC pig daily feed intakes were 29 and 73% higher by day 5 and 7 post-weaning, respectively, compared to the CON pigs (P < 0.0001). However, removing pharmacological minerals in P2 abruptly decreased ZC-CON daily feed intake within 24 h to similar intakes as the CON compared to the ZC pigs (0.17, 0.14, and 0.22 kg/d, respectively, P < 0.05). Dietary pharmacological minerals increased stomach fundus ghrelin-positive cells than CON pigs at day 7 (P = 0.005) and day 21 (P < 0.001). However, fasting plasma total and acyl-ghrelin concentrations did not differ from a control in response to zinc oxide daily drenching (Expt. 2). Expt. 3 showed that zinc and copper to have moderate to low retention; however, pharmacological zinc and copper diets increased zinc (P < 0.05) and copper retention (P = 0.06) after 28 days post-weaning compared to control pigs. Pharmacological zinc and copper did not improve digestible energy, metabolizable energy or nitrogen balance. Altogether, dietary pharmacological zinc and copper concentrations improve growth rates and mineral retention in nursery pigs. This improved performance may partially be explained by increased stomach ghrelin abundance and enhanced early feed intake in newly weaned pigs fed pharmacological concentrations of zinc and copper.
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Samy W, El Gebaly A, Ahmed NH, Talaat A. Ghrelin polymorphism/TRPV1 receptor expression in Egyptian IBS patients. Cytokine 2022; 152:155827. [PMID: 35182895 DOI: 10.1016/j.cyto.2022.155827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 11/07/2021] [Accepted: 02/06/2022] [Indexed: 11/03/2022]
Abstract
INTRODUCTION/OBJECTIVE Irritable bowel syndrome is a functional gastrointestinal disorder. Ghrelin is a peptide hormone which affects gastrointestinal motility. We have studied the association between ghrelin gene polymorphism, ghrelin expression, and their effect on TRPV1 correlating this with IBS manifestations in the Egyptian patients. METHODS Participants included 60 IBS patients meeting the Rome III criteria and 60 controls similar in age and gender were recruited. Whole blood samples were used for genotyping of Ghrelin polymorphisms rs696217. Colonic biopsies were processed for mRNA expression analysis of ghrelin and TRPV1. RESULTS The rs696217 GG genotype frequency was higher in patients (78.3%) compared to controls (57%). According to GT\TT genotype there was significant difference between IBS and control group: 21.7%, 43% respectively (p = 0.0126). In allele frequency distribution, G allele in the IBS group was 87.5% while in the control group was 74%.T allele presents in 12.5% of IBS patients and 26% in the control group (p = 0.010). The genotype frequencies did not significantly differ between IBS subtypes. TRPV1 mRNA levels in were significantly increased in IBS patients than in controls (p < 0.05), while GHRL mRNA expression was significantly decreased (p < 0.05). The IBS-C group showed significantly higher levels of TRPV1 and lower levels of GHRL mRNA expression (p < 0.05) CONCLUSIONS: we showed that ghrelin rs696217 might have a role in IBS, as those patients carrying the GG genotype showed a significant decrease in ghrelin mRNA expression, with a subsequent significant increase in TRPV1 gene expression, and could explain some of the IBS manifestations.
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Affiliation(s)
- Walaa Samy
- Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Egypt.
| | - Ahmed El Gebaly
- Department of Tropical Medicine, Faculty of Medicine, Zagazig University, Egypt
| | - Nabila H Ahmed
- Department of Tropical Medicine, Faculty of Medicine, Zagazig University, Egypt
| | - Aliaa Talaat
- Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Egypt
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Adams M, Eze E. Borassus aethiopum (Mart.) ethanol fruit extract reverses alloxan-treatment alterations in experimental animals. MEDITERRANEAN JOURNAL OF NUTRITION AND METABOLISM 2021. [DOI: 10.3233/mnm-211589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND: Borassus aethiopum fruit is claimed to be used for the management of diabetes without scientific validation. OBJECTIVE: This study seeks to evaluate the antihyperglycaemic activity of ethanol fruit extract of Borassus aethiopum in alloxan-induced diabetic rats. METHODS: 36 rats were placed in six groups (i-vi) (n = 6). Animals in group i (standard) were given 0.4 mls of distilled water (d.w) whereas the ones assigned to group ii, iii, iv, v and vi which were induced into diabetes (by intake of 140 mg/kg body weight [b.w] of alloxan) were also respectively given d.w, 50 mg/kg b.w of metformin, 25, 50 and 100 mg/kg b.w of ethanol fruit extract of Borassus aethiopum, once daily for 14 days. RESULTS: Flavonoid found in the extract (24.04 mg/ml) occurred the most with phenolic (0.35 mg/ml) being the least. While alloxan substantially (p < 0.05) increased the levels of some biological molecules and enzyme activity, it lowered those of others. The extract however significantly (p < 0.05) reversed all the alloxan-induced alterations, with the extract at 100 mg/kg b.w producing figures that compared (p > 0.05) well with those of the d.w treated non-diabetic animals and metformin-treated diabetic animals. The extract also renewed the wholeness of histological damage in the pancreas. CONCLUSION: The bioactive agents of B. aethiopum presented antihyperglycaemic property by preventing diabetes via reversal of alloxan-treatment alterations in the animals.
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Affiliation(s)
- M.D. Adams
- Phytopharmacology Biochemical Toxicology and Clinical Biochemistry Research Unit, Department of Biochemistry, Baze University, Abuja, Nigeria
| | - E.D. Eze
- Department of Physiology, School of Medicine, Kabale University, Uganda
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13
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Salman MA, Mikhail HMS, Abdelsalam A, Abdallah A, Elshafey HE, Abouelregal TE, Omar MG, Elkassar H, Ahmed RA, Atallah M, Shaaban HED, Abdellatif Z, Elkholy S, Salman AA. Acceleration of Gastric Emptying and Improvement of GERD Outcome After Laparoscopic Sleeve Gastrectomy in Non-diabetic Obese Patients. Obes Surg 2021; 30:2676-2683. [PMID: 32200446 DOI: 10.1007/s11695-020-04547-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
PURPOSE Obesity has become a pandemic nowadays. Bariatric surgery is increasingly performed to manage obesity. Currently, laparoscopic sleeve gastrectomy (LSG) is a widely accepted procedure given its feasibility and efficacy. Previous studies revealed conflicting results regarding the change of gastric emptying following sleeve gastrectomy. The primary aim of the present study is to assess gastric motor function by gastric emptying scintigraphy in a cohort of non-diabetic patients undergoing laparoscopic sleeve gastrectomy (LSG) for treatment of severe obesity. METHODS This prospective observational study included 100 obese, non-diabetic patients attending the surgery clinic at Cairo University Hospitals and Al Azhar University Hospitals. LSG was performed following a standardized protocol, with no complications observed. All patients had gastric emptying scintigraphy done through a standard semisolid meal (250 kcal), marked with 0.5 mCiTc 99, pre-operatively and 3 months after LSG. RESULTS The mean age was 38.71 years (9.2) and males comprised 57% of the cohort. The body mass index, low-density lipoproteins, and glycated hemoglobin declined significantly at 3-month postsurgery. The scintigraphy study revealed a significantly reduced percent retention at equivalent time points 3 months after LSG. In addition, the percent of patients suffering from GERD decreased significantly after LSG. CONCLUSION Gastric emptying becomes faster after LSG in morbidly obese non-diabetic patients. GERD symptoms improve after surgery.
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Affiliation(s)
| | | | - Ahmed Abdelsalam
- General Surgery Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Abdallah
- General Surgery Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hossam E Elshafey
- General Surgery Department, Faculty of Medicine, Helwan University, Helwan, Egypt
| | | | - Mahmoud Gouda Omar
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hesham Elkassar
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | | | - Mohamed Atallah
- National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | | | - Zeinab Abdellatif
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Shaimaa Elkholy
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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14
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Perego S, Sansoni V, Ziemann E, Lombardi G. Another Weapon against Cancer and Metastasis: Physical-Activity-Dependent Effects on Adiposity and Adipokines. Int J Mol Sci 2021; 22:ijms22042005. [PMID: 33670492 PMCID: PMC7922129 DOI: 10.3390/ijms22042005] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 02/15/2021] [Accepted: 02/16/2021] [Indexed: 12/15/2022] Open
Abstract
Physically active behavior has been associated with a reduced risk of developing certain types of cancer and improved psychological conditions for patients by reducing anxiety and depression, in turn improving the quality of life of cancer patients. On the other hand, the correlations between inactivity, sedentary behavior, and overweight and obesity with the risk of development and progression of various cancers are well studied, mainly in middle-aged and elderly subjects. In this article, we have revised the evidence on the effects of physical activity on the expression and release of the adipose-tissue-derived mediators of low-grade chronic inflammation, i.e., adipokines, as well as the adipokine-mediated impacts of physical activity on tumor development, growth, and metastasis. Importantly, exercise training may be effective in mitigating the side effects related to anti-cancer treatment, thereby underlining the importance of encouraging cancer patients to engage in moderate-intensity activities. However, the strong need to customize and adapt exercises to a patient’s abilities is apparent. Besides the preventive effects of physically active behavior against the adipokine-stimulated cancer risk, it remains poorly understood how physical activity, through its actions as an adipokine, can actually influence the onset and development of metastases.
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Affiliation(s)
- Silvia Perego
- Laboratory of Experimental Biochemistry and Molecular Biology, Milano, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy; (S.P.); or
| | - Veronica Sansoni
- Laboratory of Experimental Biochemistry and Molecular Biology, Milano, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy; (S.P.); or
- Correspondence: ; Tel.: +39-0266214068
| | - Ewa Ziemann
- Department of Athletics, Strength and Conditioning, Poznań University of Physical Education, 61-871 Poznań, Poland; or
| | - Giovanni Lombardi
- Laboratory of Experimental Biochemistry and Molecular Biology, Milano, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy; (S.P.); or
- Department of Athletics, Strength and Conditioning, Poznań University of Physical Education, 61-871 Poznań, Poland; or
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15
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Janet R, Fournel A, Fouillen M, Derrington E, Corgnet B, Bensafi M, Dreher JC. Cognitive and hormonal regulation of appetite for food presented in the olfactory and visual modalities. Neuroimage 2021; 230:117811. [PMID: 33524577 DOI: 10.1016/j.neuroimage.2021.117811] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 12/18/2020] [Accepted: 01/25/2021] [Indexed: 01/03/2023] Open
Abstract
The ability to regulate appetite is essential to avoid food over-consumption. The desire for a particular food can be triggered by its odor before it is even seen. Using fMRI, we identify the neural systems modulated by cognitive regulation when experiencing appetizing food stimuli presented in both olfactory and visual modalities, while being hungry. Regulatory instruction modulated bids for food items and inhalation patterns. Distinct brain regions were observed for up and down appetite-regulation, respectively the dorsomedial prefrontal cortex (dmPFC) and dorsolateral PFC. Food valuation engaged the ventromedial PFC and bilateral striatum. Furthermore, we identified a neurobiological marker for successful appetite upregulation. Individuals with higher blood levels of ghrelin were better at exercising up-regulation, and engaged the dmPFC more. These findings characterize the neural circuitry regulating food consumption within the healthy population and highlight how cognitive regulation modulates olfactomotor measures of olfaction.
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Affiliation(s)
- R Janet
- CNRS-Institut des Sciences Cognitives Marc Jeannerod, UMR5229, 'Neuroeconomics, reward, and decision making laboratory', 67 Bd Pinel, 69675 Bron, France; Univ Lyon, Université Claude Bernard Lyon 1, ISCMJ, F-69675 Lyon, France
| | - A Fournel
- Lyon Neuroscience Research Center, CNRS UMR5292, INSERM U1028, University of Lyon, Lyon, France; Univ Lyon, Université Claude Bernard Lyon 1, ISCMJ, F-69675 Lyon, France
| | - M Fouillen
- CNRS-Institut des Sciences Cognitives Marc Jeannerod, UMR5229, 'Neuroeconomics, reward, and decision making laboratory', 67 Bd Pinel, 69675 Bron, France; Univ Lyon, Université Claude Bernard Lyon 1, ISCMJ, F-69675 Lyon, France
| | - E Derrington
- CNRS-Institut des Sciences Cognitives Marc Jeannerod, UMR5229, 'Neuroeconomics, reward, and decision making laboratory', 67 Bd Pinel, 69675 Bron, France; Univ Lyon, Université Claude Bernard Lyon 1, ISCMJ, F-69675 Lyon, France
| | | | - M Bensafi
- Lyon Neuroscience Research Center, CNRS UMR5292, INSERM U1028, University of Lyon, Lyon, France; Univ Lyon, Université Claude Bernard Lyon 1, ISCMJ, F-69675 Lyon, France
| | - J C Dreher
- CNRS-Institut des Sciences Cognitives Marc Jeannerod, UMR5229, 'Neuroeconomics, reward, and decision making laboratory', 67 Bd Pinel, 69675 Bron, France; Univ Lyon, Université Claude Bernard Lyon 1, ISCMJ, F-69675 Lyon, France.
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16
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Stoica L, Gadea R, Navolan DB, Lazar F, Duta C, Stoian D, Tarta C, Olaru F, Isaic A, Dobrescu A. Plasma ghrelin, adiponectin and leptin levels in obese rats with type 2 diabetes mellitus after sleeve gastrectomy and gastric plication. Exp Ther Med 2021; 21:264. [PMID: 33603871 PMCID: PMC7851650 DOI: 10.3892/etm.2021.9695] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 10/09/2020] [Indexed: 12/16/2022] Open
Abstract
The prevalence of obesity has increased in recent decades and has become a public health problem. In obesity patients the metabolism of almost all adipokines is markedly dysregulated. Studies regarding levels of ghrelin, leptin, and adiponectin after bariatric surgery reveal contradictory results. The purpose of the present study was to analyze modification of body weight and plasma levels of fasting glucose, ghrelin, adiponectin and leptin, in obese rats with T2DM after sleeve gastrectomy (SG), gastric plication (GP) and sham-operated (SO). Eighteen specimens where randomized to three weight-matched groups: Group SG underwent sleeve gastrectomy (n=6), group GP underwent gastric plication (n=6) and the control group SO underwent sham surgery (n=6). Upon surgery a normal rat chow diet (Bio-Serv® product no. F4031) was fed to the rats until the end of the experiment. Additional blood samples were harvested after 4 weeks. The results revealed that body mass decreased in the SG (783.17±101.39 vs. 658.33±86.57 g; P<0.0001) and the GP (781.33±103.12 vs. 702.33±84.06 g; P=0.004) rats after surgery. There were significant lower fasting glucose levels at 4 weeks postoperative in the SG group compared to the SO group (83.1±12.81 vs. 104.5±9.81 mg/dl; P=0.016). The same trend was observed in the GP group vs. the SO group (86.7±11.43 vs. 104.5±9.81 mg/dl; P=0.026). There was no difference regarding mean glucose levels between the SG group compared to the GP group (P>0.05). Plasma acylated ghrelin and leptin levels decreased four weeks after surgery compared to preoperative levels, while adiponectin levels increased four weeks after surgery in the SG and GP groups, respectively. The present study revealed that plasma glucose levels, ghrelin and leptin levels decreased after SG and GP, while adiponectin levels improved. This suggests that there may be hormonal contribution in weight loss.
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Affiliation(s)
- Laurian Stoica
- Department of Surgery, 'Victor Babes' University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania.,2nd Department of Surgery, 'Pius Branzeu' Emergency Clinical County Hospital, 300723 Timisoara, Romania
| | - Ramona Gadea
- Department of Obstetrics and Gynecology, 'Victor Babes' University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania
| | - Dan-Bogdan Navolan
- Department of Obstetrics and Gynecology, 'Victor Babes' University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania
| | - Fulger Lazar
- Department of Surgery, 'Victor Babes' University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania
| | - Ciprian Duta
- Department of Surgery, 'Victor Babes' University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania.,2nd Department of Surgery, 'Pius Branzeu' Emergency Clinical County Hospital, 300723 Timisoara, Romania
| | - Dana Stoian
- Department of Endocrinology, 'Victor Babes' University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania
| | - Cristi Tarta
- Department of Surgery, 'Victor Babes' University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania.,2nd Department of Surgery, 'Pius Branzeu' Emergency Clinical County Hospital, 300723 Timisoara, Romania
| | - Flavius Olaru
- Department of Obstetrics and Gynecology, 'Victor Babes' University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania
| | - Alexandru Isaic
- Department of Surgery, 'Victor Babes' University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania.,2nd Department of Surgery, 'Pius Branzeu' Emergency Clinical County Hospital, 300723 Timisoara, Romania
| | - Amadeus Dobrescu
- Department of Surgery, 'Victor Babes' University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania.,2nd Department of Surgery, 'Pius Branzeu' Emergency Clinical County Hospital, 300723 Timisoara, Romania
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17
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Kim S, Nam Y, Shin SJ, Park YH, Jeon SG, Kim JI, Kim MJ, Moon M. The Potential Roles of Ghrelin in Metabolic Syndrome and Secondary Symptoms of Alzheimer's Disease. Front Neurosci 2020; 14:583097. [PMID: 33071750 PMCID: PMC7543232 DOI: 10.3389/fnins.2020.583097] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 08/26/2020] [Indexed: 12/12/2022] Open
Abstract
Although the major causative factors of Alzheimer's disease (AD) are the accumulation of amyloid β and hyperphosphorylated tau, AD can also be caused by metabolic dysfunction. The major clinical symptom of AD is cognitive dysfunction. However, AD is also accompanied by various secondary symptoms such as depression, sleep-wake disturbances, and abnormal eating behaviors. Interestingly, the orexigenic hormone ghrelin has been suggested to have beneficial effects on AD-related metabolic syndrome and secondary symptoms. Ghrelin improves lipid distribution and alters insulin sensitivity, effects that are hypothesized to delay the progression of AD. Furthermore, ghrelin can relieve depression by enhancing the secretion of hormones such as serotonin, noradrenaline, and orexin. Moreover, ghrelin can upregulate the expression of neurotrophic factors such as brain-derived neurotrophic factor and modulate the release of proinflammatory cytokines such as tumor necrosis factor α and interleukin 1β. Ghrelin alleviates sleep-wake disturbances by increasing the levels of melatonin, melanin-concentrating hormone. Ghrelin reduces the risk of abnormal eating behaviors by increasing neuropeptide Y and γ-aminobutyric acid. In addition, ghrelin increases food intake by inhibiting fatty acid biosynthesis. However, despite the numerous studies on the role of ghrelin in the AD-related pathology and metabolic disorders, there are only a few studies that investigate the effects of ghrelin on secondary symptoms associated with AD. In this mini review, our purpose is to provide the insights of future study by organizing the previous studies for the role of ghrelin in AD-related pathology and metabolic disorders.
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Affiliation(s)
- Sujin Kim
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon, South Korea
| | - Yunkwon Nam
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon, South Korea
| | - Soo Jung Shin
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon, South Korea
| | - Yong Ho Park
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon, South Korea
| | - Seong Gak Jeon
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon, South Korea.,Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), Daegu, South Korea
| | - Jin-Il Kim
- Department of Nursing, College of Nursing, Jeju National University, Jeju-si, South Korea
| | - Min-Jeong Kim
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon, South Korea
| | - Minho Moon
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon, South Korea
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18
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Zouhal H, Bagheri R, Triki R, Saeidi A, Wong A, Hackney AC, Laher I, Suzuki K, Ben Abderrahman A. Effects of Ramadan Intermittent Fasting on Gut Hormones and Body Composition in Males with Obesity. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17155600. [PMID: 32756479 PMCID: PMC7432640 DOI: 10.3390/ijerph17155600] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 07/28/2020] [Accepted: 07/29/2020] [Indexed: 02/06/2023]
Abstract
We studied the effects of Ramadan intermittent fasting (RIF) on gut hormones (leptin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), cholecystokinin (CCK), and ghrelin) in males with obesity. Thirty sedentary males were randomly allocated to either an experimental group (EG, n = 15) or a control group (CG, n = 15). The EG group completed their Ramadan fasting rituals (30 days), whereas the CG continued with their normal daily habits. Blood samples were collected at four time points: 24 h before the start of Ramadan (T0), on the 15th day of Ramadan (T1), the day after the end of Ramadan (T2) and 21 days after Ramadan (T3). There were significant pre-to-post improvements for leptin (p = 0.01, d = 1.52), GLP-1 (p = 0.022, d = 0.75), PYY (p = 0.031, d = 0.69) and CCK (p = 0.027, d = 0.81) in the EG, with no interaction effect for ghrelin (p = 0.74; d = 0.008). No significant changes (p > 0.05) occurred in plasma volume variations (ΔPV) after RIF in both EG (−0.03 ± 0.01%) and CG (0.06 ± 0.07%). RIF represents an effective strategy to modify appetite-regulating hormones, leading to improved body composition indices and reduced obesity.
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Affiliation(s)
- Hassane Zouhal
- Laboratoire Mouvement, Sport, Santé (M2S)-EA 1274, Université Rennes, F-35000 Rennes, France
- Correspondence: (H.Z.); (K.S.)
| | - Reza Bagheri
- Department of Exercise Physiology, University of Isfahan, Isfahan 8174673441, Iran;
| | - Raoua Triki
- ISSEP Ksar Said, University of La Manouba, Tunis 2000, Tunisia; (R.T.); (A.B.A.)
| | - Ayoub Saeidi
- Department of Physical Education, Damghan Branch, Islamic Azad University, Damghan 3671637849, Iran;
| | - Alexei Wong
- Department of Health and Human Performance, Marymount University, Arlington, VA 22207, USA;
| | - Anthony C. Hackney
- Department of Exercise & Sport Science, University of North Carolina, Chapel Hill, NC 27599, USA;
| | - Ismail Laher
- Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, BC V6T 1Z4, Canada;
| | - Katsuhiko Suzuki
- Faculty of Sport Sciences, Waseda University, Tokorozawa 359-1192, Japan
- Correspondence: (H.Z.); (K.S.)
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19
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Wong YS, Lin MY, Liu PF, Ko JL, Huang GT, Tu DG, Ou CC. D-methionine improves cisplatin-induced anorexia and dyspepsia syndrome by attenuating intestinal tryptophan hydroxylase 1 activity and increasing plasma leptin concentration. Neurogastroenterol Motil 2020; 32:e13803. [PMID: 31989744 DOI: 10.1111/nmo.13803] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 11/29/2019] [Accepted: 12/23/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND Cisplatin is a widely used antineoplastic drug. However, cisplatin-induced dyspepsia syndromes, including delayed gastric emptying, gastric distension, early satiety, nausea, and vomiting, often force patients to take doses lower than those prescribed or even refuse treatment. D-methionine has an appetite-enhancing effect and alleviates weight loss during cisplatin treatment. METHODS This work established a model of anorexia and dyspepsia symptoms with intraperitoneal injection of cisplatin (5 mg/kg) once a week for three cycles. Presupplementation with or without D-methionine (300 mg/kg) was performed. Orexigenic and anorexigenic hormones (ghrelin, leptin, and glucagon-like peptide-1), tryptophan hydroxylase 1 (TPH1), 5-hydroxytryptamine receptors (5-HT2C and 5-HT3 ), and hypothalamic feeding-related peptides were measured by immunohistochemistry staining, enzyme-linked immunosorbent assay, and real-time PCR assay. KEY RESULTS Cisplatin administration caused marked decrease in appetite and body weight, promoted adipose and fat tissue atrophy, and delayed gastric emptying and gastric distension, and D-methionine preadministration prior to cisplatin administration significantly ameliorated these side effects. Besides, cisplatin induced an evident increase in serum ghrelin level, TPH1 activity, and 5-HT3 receptor expression in the intestine and decreased plasma leptin levels and gastric ghrelin mRNA gene expression levels. D-methionine supplementation recovered these changes. The expression of orexigenic neuropeptide Y/agouti-related peptide and anorexigenic cocaine- and amphetamine-regulated transcript proopiomelanocortin neurons were altered by D-methionine supplementation in cisplatin-induced anorexia rats. CONCLUSIONS AND INFERENCES D-methionine supplementation prevents cisplatin-induced anorexia and dyspepsia syndrome possibly by attenuating intestinal tryptophan hydroxylase 1 activity and increasing plasma leptin concentration. Therefore, D-methionine can be used as an adjuvant therapy for treating cisplatin-induced adverse effects.
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Affiliation(s)
- Yi-Sin Wong
- Department of Family Medicine, Ditmanson Medical Foundation, Chia-Yi Christian Hospital, Chiayi City, Taiwan.,Department of Food Science and Technology, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Meei-Yn Lin
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan
| | - Pei-Fen Liu
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan
| | - Jiunn-Liang Ko
- Department of Medical Oncology and Chest Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.,Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan ROC
| | - Guan-Ting Huang
- Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Dom-Gene Tu
- Department of Nuclear Medicine, Ditmanson Medical Foundation, Chia-Yi Christian Hospital, Chiayi City, Taiwan.,Department of Biomedical Sciences, National Chung Cheng University, Minhsiung Chiayi, Taiwan
| | - Chu-Chyn Ou
- Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan.,School of Nutrition, Chung Shan Medical University, Taichung, Taiwan
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20
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Ziman B, Karabinis P, Barghouth P, Oviedo NJ. Sirtuin-1 regulates organismal growth by altering feeding behavior and intestinal morphology in planarians. J Cell Sci 2020; 133:jcs239467. [PMID: 32265271 PMCID: PMC7272345 DOI: 10.1242/jcs.239467] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 03/19/2020] [Indexed: 01/03/2023] Open
Abstract
Nutrient availability upon feeding leads to an increase in body size in the planarian Schmidtea mediterranea However, it remains unclear how food consumption integrates with cell division at the organismal level. Here, we show that the NAD-dependent protein deacetylases sirtuins are evolutionarily conserved in planarians, and specifically demonstrate that the homolog of human sirtuin-1 (SIRT1) (encoded by Smed-Sirt-1), regulates organismal growth by impairing both feeding behavior and intestinal morphology. Disruption of Smed-Sirt-1 with RNAi or pharmacological inhibition of Sirtuin-1 leads to reduced animal growth. Conversely, enhancement of Sirtuin-1 activity with resveratrol accelerates growth. Differences in growth rates were associated with changes in the amount of time taken to locate food and overall food consumption. Furthermore, Smed-Sirt-1(RNAi) animals displayed reduced cell death and increased stem cell proliferation accompanied by impaired expression of intestinal lineage progenitors and reduced branching of the gut. Taken together, our findings indicate that Sirtuin-1 is a crucial metabolic hub capable of controlling animal behavior, tissue renewal and morphogenesis of the adult intestine.
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Affiliation(s)
- Benjamin Ziman
- Department of Molecular and Cell Biology, University of California, Merced, CA 95343, USA
- Quantitative and Systems Biology Graduate Program, University of California, Merced, CA 95343, USA
| | - Peter Karabinis
- Department of Molecular and Cell Biology, University of California, Merced, CA 95343, USA
- Quantitative and Systems Biology Graduate Program, University of California, Merced, CA 95343, USA
| | - Paul Barghouth
- Department of Molecular and Cell Biology, University of California, Merced, CA 95343, USA
- Quantitative and Systems Biology Graduate Program, University of California, Merced, CA 95343, USA
| | - Néstor J Oviedo
- Department of Molecular and Cell Biology, University of California, Merced, CA 95343, USA
- Quantitative and Systems Biology Graduate Program, University of California, Merced, CA 95343, USA
- Health Sciences Research Institute, University of California, Merced, CA 95343, USA
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21
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Kiang JG, Smith JT, Cannon G, Anderson MN, Ho C, Zhai M, Cui W, Xiao M. Ghrelin, a novel therapy, corrects cytokine and NF-κB-AKT-MAPK network and mitigates intestinal injury induced by combined radiation and skin-wound trauma. Cell Biosci 2020; 10:63. [PMID: 32426105 PMCID: PMC7216502 DOI: 10.1186/s13578-020-00425-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Accepted: 05/04/2020] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Compared to radiation injury alone (RI), radiation injury combined wound (CI) further enhances acute radiation syndrome and subsequently mortality. We previously reported that therapy with Ghrelin, the 28-amino-acid-peptide secreted from the stomach, significantly increased 30-day survival and mitigated hematopoietic death by enhancing and sustaining granulocyte-colony stimulating factor (G-CSF) and keratinocyte chemoattractant (KC) in the blood and bone marrow; increasing circulating white blood cell depletion; inhibiting splenocytopenia; and accelerating skin-wound healing on day 30 after CI. Herein, we aimed to study the efficacy of Ghrelin on intestinal injury at early time points after CI. METHODS B6D2F1/J female mice were exposed to 60Co-γ-photon radiation (9.5 Gy, 0.4 Gy/min, bilateral), followed by 15% total-body-surface-area skin wounds. Several endpoints were measured: at 4-5 h and on days 1, 3, 7, and 15. RESULTS Ghrelin therapy mitigated CI-induced increases in IL-1β, IL-6, IL-17A, IL-18, KC, and TNF-α in serum but sustained G-CSF, KC and MIP-1α increases in ileum. Histological analysis of ileum on day 15 showed that Ghrelin treatment mitigated ileum injury by increasing villus height, crypt depth and counts, as well as decreasing villus width and mucosal injury score. Ghrelin therapy increased AKT activation and ERK activation; suppressed JNK activation and caspase-3 activation in ileum; and reduced NF-κB, iNOS, BAX and Bcl-2 in ileum. This therapy recovered the tight junction protein and mitigated bacterial translocation and lipopolysaccharides levels. The results suggest that the capacity of Ghrelin therapy to reduce CI-induced ileum injury is mediated by a balanced NF-κB-AKT-MAPK network that leads to homeostasis of pro-inflammatory and anti-inflammatory cytokines. CONCLUSIONS Our novel results are the first to suggest that Ghrelin therapy effectively decreases intestinal injury after CI.
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Affiliation(s)
- Juliann G. Kiang
- Scientific Research Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20814 USA
- Department of Pharmacology and Molecular Therapeutics, Uniformed Services, University of the Health Sciences, Bethesda, MD 20814 USA
- Department of Medicine, Uniformed Services, University of the Health Sciences, Bethesda, MD 20814 USA
| | - Joan T. Smith
- Scientific Research Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20814 USA
| | - Georgetta Cannon
- Scientific Research Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20814 USA
| | - Marsha N. Anderson
- Scientific Research Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20814 USA
| | - Connie Ho
- Department of Biochemistry, University of California, Berkeley, CA 94720 USA
| | - Min Zhai
- Scientific Research Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20814 USA
| | - Wanchang Cui
- Scientific Research Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20814 USA
| | - Mang Xiao
- Scientific Research Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20814 USA
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Tian P, Lu X, Jin N, Shi J. Knockdown of ghrelin-O-acyltransferase attenuates colitis through the modulation of inflammatory factors and tight junction proteins in the intestinal epithelium. Cell Biol Int 2020; 44:1681-1690. [PMID: 32281710 DOI: 10.1002/cbin.11362] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Revised: 04/03/2020] [Accepted: 04/11/2020] [Indexed: 12/13/2022]
Abstract
Ghrelin-O-acyltransferase (GOAT) is a membrane-bound enzyme that attaches eight-carbon octanoate to a serine residue in ghrelin and thereby acylates inactive ghrelin to produce active ghrelin. In this study, we investigated the function of GOAT in the intestinal mucosal barrier. The intestinal mucosal barrier prevents harmful substances such as bacteria and endotoxin from entering the other tissues, organs, and blood circulation through the intestinal mucosa. Here, we established 5% dextran sodium sulfate (DSS)-induced colitis in mice and found that the body weight and colon weight were significantly decreased in these mice. Furthermore, increased inflammation and apoptosis were observed in the tissues of DSS-induced colitis mice, with increased expression of tumor necrosis factor-α, interleukin-6, phosphorylation of nuclear factor kappa B-p65 (p-NF-κB-p65), and cleaved caspase-3, and decreased expression of tight junction (TJ) proteins such as zonula occluden-1 and occludin. The knockdown of GOAT significantly attenuated colitis-induced inflammation responses and apoptosis, while GOAT overexpression significantly enhanced the induction of colitis. These results suggest that knockdown of GOAT may attenuate colitis-induced inflammation, ulcers, and fecal occult blood by decreasing the intestinal mucosal permeability via the modulation of inflammatory factors and TJ proteins.
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Affiliation(s)
- Peiying Tian
- Department of Digestion, Shanghai Pudong Hospital, Shanghai, China
| | - Xiaolan Lu
- Department of Digestion, Shanghai Pudong Hospital, Shanghai, China
| | - Nuyun Jin
- Department of Digestion, Shanghai Pudong Hospital, Shanghai, China
| | - Jianping Shi
- Department of Digestion, Shanghai Pudong Hospital, Shanghai, China
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Postoperative hunger after outpatient surgery in patients anesthetized with propofol vs sevoflurane: a randomized-controlled trial. Can J Anaesth 2020; 67:550-559. [PMID: 31997087 DOI: 10.1007/s12630-020-01584-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Revised: 11/06/2019] [Accepted: 11/21/2019] [Indexed: 10/25/2022] Open
Abstract
PURPOSE Previous preclinical and preliminary clinical data suggest an appetite-stimulating effect of propofol compared with halogenated drugs. This study compared the effects of propofol with those of sevoflurane on recovery of hunger during the postoperative period. METHODS Patients undergoing outpatient transvaginal oocyte retrieval were randomized to propofol-remifentanil (propofol group) or sevoflurane-remifentanil (sevoflurane group) anesthesia. The primary endpoint was the time before feeling hungry (≥ 50/100 mm on a visual analogue scale). Secondary endpoints included plasma levels of ghrelin, leptin, and insulin (ten minutes, one hour, and two hours after anesthesia), caloric intake at first feed, and discharge readiness time. RESULTS In the 58 patients allocated to either the propofol or sevoflurane group, there was no difference in the median [interquartile range] recovery time of hunger (97 [75-138] vs 97 [80-140] min, respectively; median difference, 1; 95% confidence interval [CI], - 15 to 14; P = 0.91); caloric intake (245 [200-343] vs 260 [171-314] kcal; P = 0.39); or discharge readiness time (125 [85-153] vs 125 [95-174] min, P = 0.29). The groups showed no difference in crude plasma levels of ghrelin, leptin, and insulin at any time-point. When peptide plasma levels were expressed as a % change from baseline, there was a higher insulin plasma level one hour after anesthesia in the sevoflurane group (median difference, 4.9%; 95% CI, - 16.2 to 43.4) compared with the propofol group (median difference, - 21.2%; 95% CI, - 35.7 to 9.1; adjusted P = 0.01). CONCLUSION Propofol did not accelerate the recovery of hunger compared with sevoflurane after outpatient minor surgery. Moreover, propofol did not have distinguishable effects on other clinical or biological parameters associated with food intake. TRIAL REGISTRATION www.ClinicalTrials.gov (NCT02272166); registered 22 October, 2014.
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Rinde M, Kupferschmidt N, Iqbal MN, Robert-Nicoud G, Johnston EV, Lindgren M, Bengtsson T. Mesoporous silica with precisely controlled pores reduces food efficiency and suppresses weight gain in mice. Nanomedicine (Lond) 2020; 15:131-144. [PMID: 31933414 DOI: 10.2217/nnm-2019-0262] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Aim: Obesity is a risk factor for cardiovascular disease and diabetes. We aimed to elucidate the effects of distinct mesoporous silica particles (MSPs) supplemented in food on metabolic parameters in obesity. Materials & methods: MSPs with precisely controlled pore size were synthesized, characterized and compared with a control in a C57Bl/6 mouse diet-induced obesity model, studying weight, adiposity, metabolic regulation and food efficiency. Results: The most effective MSPs reduced adipose tissue formation to 6.5 ± 0.5 g compared with 9.4 ± 1.2 g, leptin levels nearly halved from 32.8 ± 7.4 to 16.9 ± 1.9 ng/ml and a 33% reduction of food efficiency. Control MSP showed no effects. Conclusion: Results demonstrate potential of distinct MSPs to improve metabolic risk factors. Further studies investigating mechanism of action and confirming human safety are needed.
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Affiliation(s)
- Mia Rinde
- Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91, Stockholm, Sweden
| | - Natalia Kupferschmidt
- Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91, Stockholm, Sweden
| | - Muhammad Naeem Iqbal
- Department of Material Chemistry, Stockholm University, SE-106 91, Stockholm, Sweden
| | | | - Eric V Johnston
- Sigrid Therapeutics AB, Sankt Göransgatan 159, SE-112 17, Stockholm, Sweden
| | - Maria Lindgren
- Sigrid Therapeutics AB, Sankt Göransgatan 159, SE-112 17, Stockholm, Sweden
| | - Tore Bengtsson
- Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91, Stockholm, Sweden
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Fu Y, Kraitchman DL. Rationale and Preclinical Data Supporting Bariatric Arterial Embolization. Tech Vasc Interv Radiol 2020; 23:100656. [PMID: 32192641 DOI: 10.1016/j.tvir.2020.100656] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The prevalence of obesity is increasing globally, leading to significantly increased morbidity, mortality, and health care costs. However, there is a lack of effective treatment options that can treat patients with obesity less invasively than with bariatric surgery. Bariatric arterial embolization (BAE) is an image-guided, minimally invasive, percutaneous procedure that is currently being investigated in preclinical animal models and early clinical trials. If successful, BAE may represent a viable interventional approach for obesity treatment. The purpose of this article is to introduce the physiological and anatomical rationale for BAE, review techniques involved in performing BAE for weight modulation, and provide up-to-date preclinical evidence that supports the translation of BAE into patients.
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Affiliation(s)
- Yingli Fu
- Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, MD.
| | - Dara L Kraitchman
- Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, MD
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Akalu Y, Molla MD, Dessie G, Ayelign B. Physiological Effect of Ghrelin on Body Systems. Int J Endocrinol 2020; 2020:1385138. [PMID: 32565790 PMCID: PMC7267865 DOI: 10.1155/2020/1385138] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 02/08/2020] [Accepted: 05/13/2020] [Indexed: 02/06/2023] Open
Abstract
Ghrelin is a relatively novel multifaceted hormone that has been found to exert a plethora of physiological effects. In this review, we found/confirmed that ghrelin has effect on all body systems. It induces appetite; promotes the use of carbohydrates as a source of fuel while sparing fat; inhibits lipid oxidation and promotes lipogenesis; stimulates the gastric acid secretion and motility; improves cardiac performance; decreases blood pressure; and protects the kidneys, heart, and brain. Ghrelin is important for learning, memory, cognition, reward, sleep, taste sensation, olfaction, and sniffing. It has sympatholytic, analgesic, antimicrobial, antifibrotic, and osteogenic effects. Moreover, ghrelin makes the skeletal muscle more excitable and stimulates its regeneration following injury; delays puberty; promotes fetal lung development; decreases thyroid hormone and testosterone; stimulates release of growth hormone, prolactin, glucagon, adrenocorticotropic hormone, cortisol, vasopressin, and oxytocin; inhibits insulin release; and promotes wound healing. Ghrelin protects the body by different mechanisms including inhibition of unwanted inflammation and induction of autophagy. Having a clear understanding of the ghrelin effect in each system has therapeutic implications. Future studies are necessary to elucidate the molecular mechanisms of ghrelin actions as well as its application as a GHSR agonist to treat most common diseases in each system without any paradoxical outcomes on the other systems.
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Affiliation(s)
- Yonas Akalu
- Department of Physiology, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Meseret Derbew Molla
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Gashaw Dessie
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Birhanu Ayelign
- Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Science, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
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De Leon AA, Hanlon EC. Impact of Sleep Restriction on Food Intake and Food Choice. NEUROLOGICAL MODULATION OF SLEEP 2020:217-228. [DOI: 10.1016/b978-0-12-816658-1.00023-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Expression of lysine-mediated neuropeptide hormones controlling satiety and appetite in broiler chickens. Poult Sci 2019; 99:1409-1420. [PMID: 32115028 PMCID: PMC7587822 DOI: 10.1016/j.psj.2019.10.053] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 10/18/2019] [Accepted: 10/19/2019] [Indexed: 11/21/2022] Open
Abstract
Lysine is the second most limiting amino acid after methionine and is considered the most limiting amino acid for growth in poultry. Lysine requirement for broiler chickens has changed over the years. Leptin and adiponectin represent 2 adipokines that mediate metabolism by eliciting satiety effects whereas ghrelin peptide hormone influences appetite. We hypothesize that this affects growth performance of chicks. This study evaluates the effect of varying dietary lysine homeostasis on performance of broiler chickens through satiety- and appetite-mediating hormones. In 3 replications, 270 one-day-old chicks were reared for 8 wk feeding on diets comprising 0.85, 1.14, and 1.42% lysine during the starter period and 0.75, 1.00, and 1.25% lysine during the grower period. These concentrations of lysine represent 75% (low lysine), 100% (control), and 125% (high lysine) of National Research Council recommendation for broiler chickens. Feed and water were provided for ad libitum consumption. At 8 wk of age, liver, pancreas, brain, and hypothalamus tissues were collected from 18 birds randomly selected from each treatment, snap frozen in liquid nitrogen, and stored at -80°C until use. Total RNA was extracted, and cDNA was synthesized for quantitative real-time PCR assays. Low lysine concentration caused slow growth and high mortality. There was significant upregulation of ghrelin in the hypothalamus and pancreas, and leptin and adiponectin in the hypothalamus and liver, and downregulation of ghrelin in the intestines. At low lysine concentrations, adiponectin was not expressed in both pancreas and intestines. High lysine concentration exhibited increased growth, upregulation of ghrelin in the liver, and downregulation of ghrelin in the intestines, and both adiponectin and leptin in the liver. The expression of ghrelin was negatively correlated with the expression of adiponectin and leptin (P < 0.05) in the liver, hypothalamus, and pancreas. Expression of leptin was positively correlated with adiponectin in the hypothalamus and liver (P < 0.05), exhibiting satiety effects when the concentrations of lysine were low.
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Gortan Cappellari G, Barazzoni R. Ghrelin forms in the modulation of energy balance and metabolism. Eat Weight Disord 2019; 24:997-1013. [PMID: 30353455 DOI: 10.1007/s40519-018-0599-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Accepted: 10/16/2018] [Indexed: 02/06/2023] Open
Abstract
Ghrelin is a gastric hormone circulating in acylated (AG) and unacylated (UnAG) forms. This narrative review aims at presenting current emerging knowledge on the impact of ghrelin forms on energy balance and metabolism. AG represents ~ 10% of total plasma ghrelin, has an appetite-stimulating effect and is the only form for which a receptor has been identified. Moreover, other metabolic AG-induced effects have been reported, including the modulation of glucose homeostasis with stimulation of liver gluconeogenesis, the increase of fat mass and the improvement of skeletal muscle mitochondrial function. On the other hand, UnAG has no orexigenic effects, however recent reports have shown that it is directly involved in the modulation of skeletal muscle energy metabolism by improving a cluster of interlinked functions including mitochondrial redox activities, tissue inflammation and insulin signalling and action. These findings are in agreement with human studies which show that UnAG circulating levels are positively associated with insulin sensitivity both in metabolic syndrome patients and in a large cohort from the general population. Moreover, ghrelin acylation is regulated by a nutrient sensor mechanism, specifically set on fatty acids availability. These recent findings consistently point towards a novel independent role of UnAG as a regulator of muscle metabolic pathways maintaining energy status and tissue anabolism. While a specific receptor for UnAG still needs to be identified, recent evidence strongly supports the hypothesis that the modulation of ghrelin-related molecular pathways, including those involved in its acylation, may be a potential novel target in the treatment of metabolic derangements in disease states characterized by metabolic and nutritional complications.Level of evidence Level V, narrative review.
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Affiliation(s)
- Gianluca Gortan Cappellari
- Department of Medical, Surgical and Health Sciences, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy.
| | - Rocco Barazzoni
- Department of Medical, Surgical and Health Sciences, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy.
- Azienda Sanitaria Universitaria Integrata di Trieste (ASUITS), Trieste, Italy.
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Development and validation of an assay for a novel ghrelin receptor inverse agonist PF-5190457 and its major hydroxy metabolite (PF-6870961) by LC-MS/MS in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 2019; 1130-1131:121820. [DOI: 10.1016/j.jchromb.2019.121820] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 08/26/2019] [Accepted: 09/28/2019] [Indexed: 01/10/2023]
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Kordzadeh A, Lorenzi B, Hanif MA, Charalabopoulos A. Left Gastric Artery Embolisation for the Treatment of Obesity: a Systematic Review. Obes Surg 2019; 28:1797-1802. [PMID: 29616467 DOI: 10.1007/s11695-018-3211-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Endovascular left gastric artery (LGA) embolisation has gained significant attention in the treatment of obesity/morbid obesity and reduction of ghrelin. The objective of this systematic review is to evaluate the recent literature, strengths, limitations and practical aspects of this new procedure in combination with its physiological and anatomical paradigm. METHODS A systematic electronic search of literature from 1966 to June 2017 in Medline, CINHAL, Embase, Scopus and Cochrane library in English language and adult subjects was conducted. This search was conducted in accordance with Preferred Reporting in Systematic Review and Meta-Analysis (PRISMA) guidelines. Quality assessment of the articles was performed, using Oxford critical appraisal skills programme (CASP), and their recommendation for practice was examined through National Institute for health Care Excellence (NICE). Inter-related reliability (Cronbach's Alpha) was assessed between the two independent reviewers. RESULTS A total of n = 62 individuals were subjected to LGA embolisation. At 1-3 months, 7-11% and, at 12 months, 2% weight reduction was associated with ghrelin concentration reduction of 36% at 6 months. There was Haemoglobin A1c reduction (7.4 to 6.3%) and improved quality of life (SF-36 questionnaire) at 6 months (9.5 points) (range, 3.2-17.2). Despite immediate epigastric pain and mucosal ulceration, no long-term adverse outcome was identified. The overall length of stay was 2-3 days. CONCLUSIONS The outcome of this review (level of evidence 3) suggests LGA embolisation is feasible and effective and perhaps a safe procedure in the treatment of obesity and reduction of ghrelin. However, further trials are highly advocated.
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Affiliation(s)
- Ali Kordzadeh
- Department of Vascular, Endovascular and Renal Access, Mid Essex Hospitals Services NHS Trust, Broomfield, UK. .,Broomfield Hospital, Essex, CM1 7ET, UK.
| | - Bruno Lorenzi
- Department of General and Upper Gastrointestinal Surgery, Regional Oesophagogastric Centre, Mid Essex Hospitals Services NHS Trust, Broomfield, UK
| | - Muhammad A Hanif
- Department of Interventional Radiology, Mid Essex Hospitals Services NHS Trust, Broomfield, UK
| | - Alexandros Charalabopoulos
- Department of General and Upper Gastrointestinal Surgery, Regional Oesophagogastric Centre, Mid Essex Hospitals Services NHS Trust, Broomfield, UK
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Adusumalli S, Jamwal R, Obach RS, Ryder TF, Leggio L, Akhlaghi F. Role of Molybdenum-Containing Enzymes in the Biotransformation of the Novel Ghrelin Receptor Inverse Agonist PF-5190457: A Reverse Translational Bed-to-Bench Approach. Drug Metab Dispos 2019; 47:874-882. [PMID: 31182423 PMCID: PMC6636241 DOI: 10.1124/dmd.119.087015] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Accepted: 05/28/2019] [Indexed: 12/29/2022] Open
Abstract
(R)-2-(2-methylimidazo[2,1-b]thiazol-6-yl)-1-(2-(5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonan-7-yl)ethan-1-one (PF-5190457) was identified as a potent and selective inverse agonist of the ghrelin receptor [growth hormone secretagogue receptor 1a (GHS-R1a)]. The present translational bed-to-bench work characterizes the biotransformation of this compound in vivo and then further explores in vitro metabolism in fractions of human liver and primary hepatocytes. Following oral administration of PF-5190457 in a phase 1b clinical study, hydroxyl metabolites of the compound were observed, including one that had not been observed in previously performed human liver microsomal incubations. PF-6870961 was biosynthesized using liver cytosol, and the site of hydroxylation was shown to be on the pyrimidine using nuclear magnetic resonance spectroscopy. The aldehyde oxidase (AO) inhibitor raloxifene and the xanthine oxidase inhibitor febuxostat inhibited the formation of PF-6870961 in human liver cytosol, suggesting both enzymes were involved in the metabolism of the drug. However, greater inhibition was observed with raloxifene, indicating AO is a dominant enzyme in the biotransformation. The intrinsic clearance of the drug in human liver cytosol was estimated to be 0.002 ml/min per milligram protein. This study provides important novel information at three levels: 1) it provides additional new information on the recently developed novel compound PF-5190457, the first GHS-R1a blocker that has moved to development in humans; 2) it provides an example of a reverse translational approach where a discovery in humans was brought back, validated, and further investigated at the bench level; and 3) it demonstrates the importance of considering the molybdenum-containing oxidases during the development of new drug entities. SIGNIFICANCE STATEMENT: PF-5190457 is a novel ghrelin receptor inverse agonist that is currently undergoing clinical development for treatment of alcohol use disorder. PF-6870961, a major hydroxyl metabolite of the compound, was observed in human plasma, but was absent in human liver microsomal incubations. PF-6870961 was biosynthesized using liver cytosol, and the site of hydroxylation on the pyrimidine ring was characterized. Inhibitors of aldehyde oxidase and xanthine oxidase inhibited the formation of PF-6870961 in human liver cytosol, suggesting both enzymes were involved in the metabolism of the drug. This information is important for patient selection in subsequent clinical studies.
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Affiliation(s)
- Sravani Adusumalli
- Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., R.J., F.A.); Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer, Inc., Groton, Connecticut (R.S.O., T.F.R.); Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research and National Institute on Drug Abuse Intramural Research Program, Bethesda, Maryland (L.L.); Medication Development Program, National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland (L.L.); and Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, Rhode Island (L.L.)
| | - Rohitash Jamwal
- Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., R.J., F.A.); Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer, Inc., Groton, Connecticut (R.S.O., T.F.R.); Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research and National Institute on Drug Abuse Intramural Research Program, Bethesda, Maryland (L.L.); Medication Development Program, National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland (L.L.); and Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, Rhode Island (L.L.)
| | - R Scott Obach
- Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., R.J., F.A.); Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer, Inc., Groton, Connecticut (R.S.O., T.F.R.); Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research and National Institute on Drug Abuse Intramural Research Program, Bethesda, Maryland (L.L.); Medication Development Program, National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland (L.L.); and Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, Rhode Island (L.L.)
| | - Tim F Ryder
- Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., R.J., F.A.); Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer, Inc., Groton, Connecticut (R.S.O., T.F.R.); Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research and National Institute on Drug Abuse Intramural Research Program, Bethesda, Maryland (L.L.); Medication Development Program, National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland (L.L.); and Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, Rhode Island (L.L.)
| | - Lorenzo Leggio
- Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., R.J., F.A.); Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer, Inc., Groton, Connecticut (R.S.O., T.F.R.); Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research and National Institute on Drug Abuse Intramural Research Program, Bethesda, Maryland (L.L.); Medication Development Program, National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland (L.L.); and Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, Rhode Island (L.L.)
| | - Fatemeh Akhlaghi
- Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., R.J., F.A.); Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer, Inc., Groton, Connecticut (R.S.O., T.F.R.); Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research and National Institute on Drug Abuse Intramural Research Program, Bethesda, Maryland (L.L.); Medication Development Program, National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland (L.L.); and Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, Rhode Island (L.L.)
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Zhou Y, Qi X, Wen H, Zhang K, Zhang X, Li J, Li Y, Fan H. Identification, expression analysis, and functional characterization of motilin and its receptor in spotted sea bass (Lateolabrax maculatus). Gen Comp Endocrinol 2019; 277:38-48. [PMID: 30771290 DOI: 10.1016/j.ygcen.2019.02.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Revised: 01/08/2019] [Accepted: 02/11/2019] [Indexed: 12/28/2022]
Abstract
Motilin (MLN), an interdigestive hormone secreted by endocrine cells of the intestinal mucosa, binds to a G protein-coupled receptor to exert its biological function of regulating gastrointestinal motility. In the present study, we identified the prepromotilin and mln receptor (mlnr) from the spotted sea bass, Lateolabrax maculatus. Mln consisted of an ORF of 336 nucleotides encoding 111 amino acids. The precursor protein contained a 17-amino-acid mature peptide. Mlnr had an ORF of 1089 bp encoding a protein of 362 amino acids. Seven transmembrane domains were predicted with TMHMM analysis. The phylogenetic analysis of mln and mlnr showed that they fell into the same clade with respective counterpart of selected fishes before clustering with other detected vertebrates. Both mln and mlnr genes were highly expressed in intestine of spotted sea bass using quantitative real-time PCR. In situ hybridization indicated that mln and mlnr mRNA were both localized in the lamina propria and the epithelial cell of intestinal villus. The expressions of both genes were regulated under short-term starvation in a time-dependent manner. In vitro experiments indicated that the expressions of ghrelin (ghrl), gastrin (gas) and cholecystokinin (cck) were enhanced by MLN after 3-h treatment, but the effect was absent after 6 or 12-h incubation. Taken together, the MLN and its receptor might play important roles in regulating intestinal motility in spotted sea bass.
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MESH Headings
- Amino Acid Sequence
- Animals
- Base Sequence
- Bass/genetics
- Cloning, Molecular
- Fasting
- Gene Expression Profiling
- Gene Expression Regulation
- Intestines/cytology
- Molecular Docking Simulation
- Motilin/chemistry
- Motilin/genetics
- Motilin/metabolism
- Phylogeny
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Receptors, Gastrointestinal Hormone/chemistry
- Receptors, Gastrointestinal Hormone/genetics
- Receptors, Gastrointestinal Hormone/metabolism
- Receptors, Neuropeptide/chemistry
- Receptors, Neuropeptide/genetics
- Receptors, Neuropeptide/metabolism
- Sequence Analysis, DNA
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Affiliation(s)
- Yangyang Zhou
- Key Laboratory of Mariculture (Ocean University of China), Ministry of Education, Qingdao, 266003, PR China
| | - Xin Qi
- Key Laboratory of Mariculture (Ocean University of China), Ministry of Education, Qingdao, 266003, PR China
| | - Haishen Wen
- Key Laboratory of Mariculture (Ocean University of China), Ministry of Education, Qingdao, 266003, PR China
| | - Kaiqiang Zhang
- Key Laboratory of Mariculture (Ocean University of China), Ministry of Education, Qingdao, 266003, PR China
| | - Xiaoyan Zhang
- Key Laboratory of Mariculture (Ocean University of China), Ministry of Education, Qingdao, 266003, PR China
| | - Jin Li
- Ji'nan Aquatic Technology Extension Station, Ji'nan 250021, China
| | - Yun Li
- Key Laboratory of Mariculture (Ocean University of China), Ministry of Education, Qingdao, 266003, PR China.
| | - Hongying Fan
- Key Laboratory of Mariculture (Ocean University of China), Ministry of Education, Qingdao, 266003, PR China.
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Kshatriya D, Li X, Giunta GM, Yuan B, Zhao D, Simon JE, Wu Q, Bello NT. Phenolic-enriched raspberry fruit extract (Rubus idaeus) resulted in lower weight gain, increased ambulatory activity, and elevated hepatic lipoprotein lipase and heme oxygenase-1 expression in male mice fed a high-fat diet. Nutr Res 2019; 68:19-33. [PMID: 31252376 DOI: 10.1016/j.nutres.2019.05.005] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Revised: 05/06/2019] [Accepted: 05/17/2019] [Indexed: 12/15/2022]
Abstract
Red raspberries (Rubus idaeus) contain numerous phenolic compounds with purported health benefits. Raspberry ketone (4-(4-hydroxyphenyl)-2-butanone) is a primary raspberry flavor phenolic found in raspberries and is designated as a synthetic flavoring agent by the Food and Drug Administration. Synthetic raspberry ketone has been demonstrated to result in weight loss in rodents. We tested whether phenolic-enriched raspberry extracts, compared with raspberry ketone, would be more resilient to the metabolic alterations caused by an obesogenic diet. Male C57BL/6J mice (8 weeks old) received a daily oral dose of vehicle (VEH; 50% propylene glycol, 40% water, and 10% dimethyl sulfoxide), raspberry extract low (REL; 0.2 g/kg), raspberry extract high (REH; 2 g/kg), or raspberry ketone (RK; 0.2 g/kg). Coincident with daily dosing, mice were placed on a high-fat diet (45% fat). After 4 weeks, REH and RK reduced body weight gain (approximately 5%-9%) and white adipose mass (approximately 20%) compared with VEH. Hepatic gene expression of heme oxygenase-1 and lipoprotein lipase was upregulated in REH compared with VEH. Indirect calorimetry indicated that respiratory exchange ratio (CO2 production to O2 consumption) was lower, suggesting increased fat oxidation with all treatments. REH treatment increased total ambulatory behavior. Energy expenditure/lean mass was higher in REH compared with REL treatment. There were no treatment differences in cumulative intake, meal patterns, or hypothalamic feed-related gene expression. Our results suggest that raspberry ketone and a phenolic-enriched raspberry extract both have the capacity to prevent weight gain but differ in the preventative mechanisms for excess fat accumulation following high-fat diet exposure.
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Affiliation(s)
- Dushyant Kshatriya
- Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA; Nutritional Sciences Graduate Program, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey New Brunswick, NJ, 08901, USA
| | - Xinyi Li
- Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA; Nutritional Sciences Graduate Program, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey New Brunswick, NJ, 08901, USA
| | - Gina M Giunta
- Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA
| | - Bo Yuan
- New Use Agriculture and Natural Plant Products Program, Department of Plant Biology, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA
| | - Danyue Zhao
- New Use Agriculture and Natural Plant Products Program, Department of Plant Biology, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA
| | - James E Simon
- New Use Agriculture and Natural Plant Products Program, Department of Plant Biology, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA
| | - Qingli Wu
- New Use Agriculture and Natural Plant Products Program, Department of Plant Biology, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA
| | - Nicholas T Bello
- Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA; Nutritional Sciences Graduate Program, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey New Brunswick, NJ, 08901, USA.
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35
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Farokhnia M, Faulkner ML, Piacentino D, Lee MR, Leggio L. Ghrelin: From a gut hormone to a potential therapeutic target for alcohol use disorder. Physiol Behav 2019; 204:49-57. [DOI: 10.1016/j.physbeh.2019.02.008] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Revised: 01/24/2019] [Accepted: 02/06/2019] [Indexed: 12/22/2022]
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Ertosun MG, Kocak G, Ozes ON. The regulation of circadian clock by tumor necrosis factor alpha. Cytokine Growth Factor Rev 2019; 46:10-16. [PMID: 31000463 DOI: 10.1016/j.cytogfr.2019.04.001] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 03/23/2019] [Accepted: 04/01/2019] [Indexed: 12/13/2022]
Abstract
All organisms display circadian rhythms which are under the control of the circadian clock located in the hypothalamus at the suprachiasmatic nucleus, (SCN). The circadian rhythms allow individuals to adjust their physiological activities and daily behavior for the diurnal changes in the living environment. To achieve these, all metabolic processes are aligned with the sleep/wake and fasting/feeding cycles. Subtle changes of daily behavior or food intake can result in misalignment of circadian rhythms. This can cause development of variety of metabolic diseases and even cancer. Although light plays a pivotal role for the activation of the master clock in SCN, the peripheral secondary clocks (or non-SCN), such as melatonin, growth hormone (GH), insulin, adiponectin and Ghrelin also are important in maintaining the circadian rhythms in the brain and peripheral organs. In recent years, growing body of evidence strongly suggest that CA2+ signaling, tumor necrosis factor alpha (TNFα) and transforming growth factor beta (TGFβ) also play very important roles in the regulation of circadian rhythms by regulating the transcription of the clock genes.
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Affiliation(s)
- Mustafa Gokhan Ertosun
- Akdeniz University School of Medicine, Department of Plastic, Reconstructive & Anesthetic Surgery, Turkey.
| | - Gamze Kocak
- Akdeniz University School of Medicine, Department of Medical Biology and Genetics, Turkey.
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37
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38
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Koutouratsas T, Kalli T, Karamanolis G, Gazouli M. Contribution of ghrelin to functional gastrointestinal disorders’ pathogenesis. World J Gastroenterol 2019; 25:539-551. [PMID: 30774270 PMCID: PMC6371003 DOI: 10.3748/wjg.v25.i5.539] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 12/20/2018] [Accepted: 01/15/2019] [Indexed: 02/06/2023] Open
Abstract
Functional gastrointestinal disorders (FGID) are heterogeneous disorders with a variety of clinical manifestations, primarily defined by signs and symptoms rather than a definite underlying cause. Their pathophysiology remains obscure and, although it is expected to differ according to the specific FGID, disruptions in the brain-gut axis are now thought to be a common denominator in their pathogenesis. The hormone ghrelin is an important component of this axis, exerting a wide repertoire of physiological actions, including regulation of gastrointestinal motility and protection of mucosal tissue. Ghrelin’s gene shows genetic polymorphism, while its protein product undergoes complex regulation and metabolism in the human body. Numerous studies have studied ghrelin’s relation to the emergence of FGIDs, its potential value as an index of disease severity and as a predictive marker for symptom relief during attempted treatment. Despite the mixed results currently available in scientific literature, the plethora of statistically significant findings shows that disruptions in ghrelin genetics and expression are plausibly related to FGID pathogenesis. The aim of this paper is to review current literature studying these associations, in an effort to uncover certain patterns of alterations in both genetics and expression, which could delineate its true contribution to FGID emergence, either as a causative agent or as a pathogenetic intermediate.
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Affiliation(s)
- Tilemachos Koutouratsas
- Department of Basic Medical Science, Laboratory of Biology, School of Medicine, University of Athens, Athens 11527, Greece
| | - Theodora Kalli
- Gastroenterology Department, Larnaca General Hospital, Larnaca 6301, Cyprus
| | - Georgios Karamanolis
- Gastroenterology Unit, 2nd Department of Surgery, “Aretaieio” University Hospital, School of Medicine, University of Athens, Athens 11527, Greece
| | - Maria Gazouli
- Department of Basic Medical Science, Laboratory of Biology, School of Medicine, University of Athens, Athens 11527, Greece
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Petkus DL, Murray-Kolb LE, De Souza MJ. The Unexplored Crossroads of the Female Athlete Triad and Iron Deficiency: A Narrative Review. Sports Med 2018; 47:1721-1737. [PMID: 28290159 DOI: 10.1007/s40279-017-0706-2] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Despite the severity and prevalence of iron deficiency in exercising women, few published reports have explored how iron deficiency interacts with another prevalent and severe condition in exercising women: the 'female athlete triad.' This review aims to describe how iron deficiency may interact with each component of the female athlete triad, that is, energy status, reproductive function, and bone health. The effects of iron deficiency on energy status are discussed in regards to thyroid function, metabolic fuel availability, eating behaviors, and energy expenditure. The interactions between iron deficiency and reproductive function are explored by discussing the potentially impaired fertility and hyperprolactinemia due to iron deficiency and the alterations in iron metabolism due to menstrual blood loss and estrogen exposure. The interaction of iron deficiency with bone health may occur via dysregulation of the growth hormone/insulin-like growth factor-1 axis, hypoxia, and hypothyroidism. Based on these discussions, several future directions for research are presented.
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Affiliation(s)
- Dylan L Petkus
- Department of Kinesiology, The Pennsylvania State University, 104 Noll Laboratory, University Park, PA, 16802, USA
| | - Laura E Murray-Kolb
- Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, USA
| | - Mary Jane De Souza
- Department of Kinesiology, The Pennsylvania State University, 104 Noll Laboratory, University Park, PA, 16802, USA.
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40
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Solomon I, Ilie MA, Draghici C, Voiculescu VM, Căruntu C, Boda D, Zurac S. The impact of lifestyle factors on evolution of atopic dermatitis: An alternative approach. Exp Ther Med 2018; 17:1078-1084. [PMID: 30679977 PMCID: PMC6327646 DOI: 10.3892/etm.2018.6980] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 09/26/2018] [Indexed: 01/19/2023] Open
Abstract
Atopic dermatitis (AD) is a multifactorial chronic inflammatory disease with an incompletely understood etiopathogenesis. With a significant impact on the quality of life of patients, AD has attracted the interest of many research studies aiming to investigate the complex cellular and molecular mechanisms and to identify new therapeutic pathways. Various studies have focused on psycho-immunology, emphasizing the involvement of stress, defined as a general response of the body to external or internal challenges to the AD pathology. Factors like lifestyle and leisure activities may change the behavior of immune cells in AD with a strong impact on the evolution of the disease. Moreover, the poor adherence of AD patient to standard treatment approach has led to the necessity to combine different therapies in the field of complementary and alternative medicine. Although there are still not enough data to conclude that adjuvant therapies are effective in a conventional sense, there are already promising results suggesting that alternative therapeutic strategies could be a main subject of further research.
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Affiliation(s)
- Iulia Solomon
- Department of Dermatology and Allergology, Elias Emergency University Hospital, 011461 Bucharest, Romania
| | - Mihaela Adriana Ilie
- Dermatology Research Laboratory, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.,Department of Biochemistry, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Carmen Draghici
- Department of Dermatology and Allergology, Elias Emergency University Hospital, 011461 Bucharest, Romania
| | - Vlad Mihai Voiculescu
- Department of Dermatology and Allergology, Elias Emergency University Hospital, 011461 Bucharest, Romania.,Dermatology Research Laboratory, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Constantin Căruntu
- Department of Physiology, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.,Department of Dermatology, 'Prof. N. Paulescu' National Institute of Diabetes, Nutrition and Metabolic Diseases, 011233 Bucharest, Romania
| | - Daniel Boda
- Dermatology Research Laboratory, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.,Department of Dermatology, 'Prof. N. Paulescu' National Institute of Diabetes, Nutrition and Metabolic Diseases, 011233 Bucharest, Romania
| | - Sabina Zurac
- Department of Pathology, Faculty of Dental Medicine, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.,Department of Pathology, Colentina Clinical Hospital, 020125 Bucharest, Romania
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41
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Wang Q, Yin Y, Zhang W. Ghrelin Restores the Disruption of the Circadian Clock in Steatotic Liver. Int J Mol Sci 2018; 19:E3134. [PMID: 30322022 PMCID: PMC6213951 DOI: 10.3390/ijms19103134] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 09/22/2018] [Accepted: 10/09/2018] [Indexed: 12/25/2022] Open
Abstract
Obese mice demonstrate disruption of the circadian clock and feeding cycle. Circulating ghrelin, a hormone secreted mainly by gastric X/Alike cells, is significantly reduced in obese humans and animals. Here, we examined whether ghrelin improves the disruption of the circadian rhythm in steatotic hepatocytes and liver. The effects of ghrelin on hepatic circadian clock genes were studied in steatotic hepatocytes and liver of mice fed a high-fat diet (HFD) for 12 weeks. The circadian clock of cultured hepatocytes was synchronized by treatment with 100 nM dexamethasone for 1 h. Ghrelin was administrated to the cultured hepatocytes (10-8 M) or to mice at a dose of 11 nmol/kg/d for two weeks via a subcutaneous minipump. The mRNA and protein levels of core clock genes were analyzed. Steatosis significantly blunted the circadian pattern of clock genes such as Bmal1, Clock, and Per in cultured hepatocytes and liver. Treatment with ghrelin markedly restored the daily rhythm of the clock genes, with a robust oscillation between peak and trough in cultured hepatocytes isolated from obese mice. It also increased the abundance and expression amplitude of clock genes in steatotic liver, causing the peak of Clock to shift to the dark period and the peak of Per2 to shift to the light period compared with the control groups. Deletion of GHSR1a further deteriorated the derangement of clock gene patterns in obese mice. Ghrelin significantly increased the oscillations of mTOR/S6 signaling. We demonstrate that ghrelin restored the derangement of the circadian rhythm in steatotic liver via mTOR signaling.
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Affiliation(s)
- Qin Wang
- Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
| | - Yue Yin
- Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
| | - Weizhen Zhang
- Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
- Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109-0346, USA.
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42
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Okushin K, Tsutsumi T, Ikeuchi K, Kado A, Enooku K, Fujinaga H, Moriya K, Yotsuyanagi H, Koike K. Helicobacter pylori infection and liver diseases: Epidemiology and insights into pathogenesis. World J Gastroenterol 2018; 24:3617-3625. [PMID: 30166857 PMCID: PMC6113725 DOI: 10.3748/wjg.v24.i32.3617] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 05/30/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
Both Helicobacter pylori (H. pylori) infection and liver diseases, including nonalcoholic fatty liver disease (NAFLD), viral hepatitis, and hepatocellular carcinoma (HCC), have high prevalences worldwide, and the relationship between H. pylori infection and liver disease has been discussed for many years. Although positive correlations between H. pylori and NAFLD have been identified in some clinical and experimental studies, negative correlations have also been obtained in high-quality clinical studies. Associations between H. pylori and the pathogenesis of chronic viral hepatitis, mainly disease progression with fibrosis, have also been suggested in some clinical studies. Concerning HCC, a possible role for H. pylori in hepatocarcinogenesis has been identified since H. pylori genes have frequently been detected in resected HCC specimens. However, no study has revealed the direct involvement of H. pylori in promoting the development of HCC. Although findings regarding the correlations between H. pylori and liver disease pathogenesis have been accumulating, the existing data do not completely lead to an unequivocal conclusion. Further high-quality clinical and experimental analyses are necessary to evaluate the efficacy of H. pylori eradication in ameliorating the histopathological changes observed in each liver disease.
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Affiliation(s)
- Kazuya Okushin
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Takeya Tsutsumi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
| | - Kazuhiko Ikeuchi
- Department of Infectious Diseases, The University of Tokyo, Tokyo 113-8655, Japan
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
| | - Akira Kado
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Kenichiro Enooku
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Hidetaka Fujinaga
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Kyoji Moriya
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
- Department of Infectious Diseases, The University of Tokyo, Tokyo 113-8655, Japan
| | - Hiroshi Yotsuyanagi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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Tzanavari T, Tasoulas J, Vakaki C, Mihailidou C, Tsourouflis G, Theocharis S. The Role of Adipokines in the Establishment and Progression of Head and Neck Neoplasms. Curr Med Chem 2018; 26:4726-4748. [PMID: 30009699 DOI: 10.2174/0929867325666180713154505] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2017] [Revised: 03/13/2018] [Accepted: 07/06/2018] [Indexed: 12/15/2022]
Abstract
Adipokines constitute a family of protein factors secreted by white adipose tissue (WAT), that regulate the functions of WAT and other sites. Leptin, adiponectin and resistin, are the main adipokines present in serum and saliva, targeting several tissues and organs, including vessels, muscles, liver and pancreas. Besides body mass regulation, adipokines affect glucose homeostasis, inflammation, angiogenesis, cell proliferation and apoptosis, and other crucial cell procedures. Their involvement in tumor formation and growth is well established and deregulation of adipokine and adipokine receptors' expression is observed in several malignancies including those located in the head and neck region. Intracellular effects of adipokines are mediated by a plethora of receptors that activate several signaling cascades including Janus kinase/ Signal transducer and activator of transcription (JAK/ STAT pathway), Phospatidylinositol kinase (PI3/ Akt/ mTOR) and Peroxisome proliferator-activated receptor (PPAR). The present review summarizes the current knowledge on the role of adipokines family members in carcinogenesis of the head and neck region. The diagnostic and prognostic significance of adipokines and their potential role as serum and saliva biomarkers are also discussed.
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Affiliation(s)
- Theodora Tzanavari
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece
| | - Jason Tasoulas
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece
| | - Chrysoula Vakaki
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece
| | - Chrysovalantou Mihailidou
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece
| | - Gerasimos Tsourouflis
- Second Department of Propaedeutic Surgery, Medical School, National and Kapodistrian, University of Athens, Athens, 11527, Greece
| | - Stamatios Theocharis
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece
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Farokhnia M, Lee MR, Farinelli LA, Ramchandani VA, Akhlaghi F, Leggio L. Pharmacological manipulation of the ghrelin system and alcohol hangover symptoms in heavy drinking individuals: Is there a link? Pharmacol Biochem Behav 2018; 172:39-49. [PMID: 30030128 DOI: 10.1016/j.pbb.2018.07.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 06/23/2018] [Accepted: 07/16/2018] [Indexed: 12/14/2022]
Abstract
Ghrelin, an orexigenic peptide synthesized in the stomach, is a key player in the gut-brain axis. In addition to its role in regulating food intake and energy homeostasis, ghrelin has been shown to modulate alcohol-related behaviors. Alcohol consumption frequently results in hangover, an underexplored phenomenon with considerable medical, psychological, and socioeconomic consequences. While the pathophysiology of hangover is not clear, contributions of mechanisms such as alcohol-induced metabolic/endocrine changes, inflammatory/immune response, oxidative stress, and gut dysbiosis have been reported. Interestingly, these mechanisms considerably overlap with ghrelin's physiological functions. Here, we investigated whether pharmacological manipulation of the ghrelin system may affect alcohol hangover symptoms. Data were obtained from two placebo-controlled laboratory studies. The first study tested the effects of intravenous (IV) ghrelin and consisted of two experiments: a progressive-ratio IV alcohol self-administration (IV-ASA) and a fixed-dose IV alcohol clamp. The second study tested the effects of an oral ghrelin receptor inverse agonist (PF-5190457) and included a fixed-dose oral alcohol administration experiment. Alcohol hangover data were collected the morning after each alcohol administration experiment using the Acute Hangover Scale (AHS). IV ghrelin, compared to placebo, significantly reduced alcohol hangover after IV-ASA (p = 0.04) and alcohol clamp (p = 0.04); PF-5190457 had no significant effect on AHS scores. Females reported significantly higher hangover symptoms than males following the IV-ASA experiment (p = 0.04), but no gender × drug condition (ghrelin vs. placebo) effect was found. AHS total scores were positively correlated with peak subjective responses, including 'stimulation' (p = 0.08), 'sedation' (p = 0.009), 'feel high' (p = 0.05), and 'feel intoxicated' (p = 0.03) during the IV-ASA. IV ghrelin blunted the positive association between alcohol sedation and hangover as shown by trend-level drug × sedation effect (p = 0.08). This is the first study showing that exogenous ghrelin administration, but not ghrelin receptor inverse agonism, affects hangover symptoms. Future research should investigate the potential mechanism(s) underlying this effect.
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Affiliation(s)
- Mehdi Farokhnia
- Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA
| | - Mary R Lee
- Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA
| | - Lisa A Farinelli
- Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA
| | - Vijay A Ramchandani
- Section on Human Psychopharmacology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
| | - Fatemeh Akhlaghi
- Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, USA
| | - Lorenzo Leggio
- Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA; Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, RI, USA.
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Abusarah J, Khodayarian F, Cui Y, El-Kadiry AEH, Rafei M. Thymic Rejuvenation: Are We There Yet? Gerontology 2018. [DOI: 10.5772/intechopen.74048] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
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Scolnick B. Treatment of anorexia nervosa with palmitoylethanoamide. Med Hypotheses 2018; 116:54-60. [PMID: 29857912 DOI: 10.1016/j.mehy.2018.04.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 04/09/2018] [Accepted: 04/11/2018] [Indexed: 12/11/2022]
Affiliation(s)
- Barbara Scolnick
- Boston University, Dept of Psychological and Brain Sciences, 64 Cummington Street, Boston, MA 02215, United States.
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Birerdinc A, Stoddard S, Younossi ZM. The Stomach as an Endocrine Organ: Expression of Key Modulatory Genes and Their Contribution to Obesity and Non-alcoholic Fatty Liver Disease (NAFLD). Curr Gastroenterol Rep 2018; 20:24. [PMID: 29675753 DOI: 10.1007/s11894-018-0629-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
PURPOSE OF REVIEW Obesity is currently seen in epidemic proportions globally and is one of the largest contributors to the development of NAFLD. The spectrum of NAFLD, particularly the progressive forms of NASH, is likely to become the leading cause of liver disease in the next decade. RECENT FINDINGS Soluble molecules, encoded by the stomach tissue, have been shown to have pleiotropic effects in both central and peripheral systems involved in energy homeostasis and obesity regulation. As such, the stomach is one of the important players in the complex, multi-system deregulation leading to obesity and NAFLD. The understanding of the stomach tissue as an active endocrine organ that contributes to the signaling milieu leading to the development of obesity and NAFLD is crucial.
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Affiliation(s)
- Aybike Birerdinc
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Claude Moore Health Education and Research Building, 3300 Gallows Road, Falls Church, VA, 22042, USA
| | - Sasha Stoddard
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Claude Moore Health Education and Research Building, 3300 Gallows Road, Falls Church, VA, 22042, USA
| | - Zobair M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Claude Moore Health Education and Research Building, 3300 Gallows Road, Falls Church, VA, 22042, USA.
- Department of Medicine and Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA.
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Zhang S, Mao Y, Fan X. Inhibition of ghrelin o-acyltransferase attenuated lipotoxicity by inducing autophagy via AMPK-mTOR pathway. DRUG DESIGN DEVELOPMENT AND THERAPY 2018; 12:873-885. [PMID: 29713145 PMCID: PMC5912383 DOI: 10.2147/dddt.s158985] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) has been considered the most commonly occurring chronic hepatopathy in the world. Ghrelin o-acyltransferase (GOAT) is an acylation enzyme which has an acylated position 3 serine on ghrelin. Recent investigation revealed that activated autophagy could attenuate liver steatosis. The aim of this study was to explore therapeutic roles that inhibit GOAT exerted in NAFLD, and its potential association with autophagy. Materials and methods Human LO2 cells were pretreated with siRNA-GOAT to induce liver steatosis using free fatty acids (FFAs). A chronic NAFLD model was established by feeding male mice C57bl/6 with high-fat diet (HFD) for 56 days with GO-CoA-Tat administrated subcutaneously. Lipid droplets were identified by Oil Red O stains. Body weight (BW) of mice was measured every week. Autophagy, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), serum biochemical indicators (glucose [Glu], total cholesterol [TC], triglyceride [TG], aspartate aminotransferase [AST], alanine aminotransferase [ALT]) and signaling pathway proteins of phosphorylated AMPK–mTOR were measured. Results The TG contents of the FFA and HFD groups were decreased by the inhibition of GOAT. Among mice treated with GO-CoA-Tat and siRNA-GOAT, IL-6 and TNF-α concentrations were remarkably decreased. Indicators of liver injury such as ALT and AST were also remarkably decreased among mice treated with GO-CoA-Tat. Likewise, GO-CoA-Tat significantly reduced the BW of mice and serum TG, TC and Glu. Autophagy was induced along with reduced lipids in the cells of the FFA and HFD groups. The inhibition of GOAT upregulated autophagy via AMPK–mTOR restoration. Conclusion These results indicate that the inhibition of GOAT attenuates lipotoxicity by autophagy stimulation via AMPK–mTOR restoration and offers innovative evidence for using GO-CoA-Tat or siRNA-GOAT in NAFLD clinically.
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Affiliation(s)
- Shaoren Zhang
- Department of Gastroenterology and Hepatology, Jinshan Hospital of Fudan University, Shanghai, China
| | - Yuqing Mao
- Department of Gastroenterology and Hepatology, Jinshan Hospital of Fudan University, Shanghai, China
| | - Xiaoming Fan
- Department of Gastroenterology and Hepatology, Jinshan Hospital of Fudan University, Shanghai, China
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Impact of Laparoscopic Sleeve Gastrectomy on Gastrointestinal Motility. Gastroenterol Res Pract 2018; 2018:4135813. [PMID: 29849586 PMCID: PMC5907392 DOI: 10.1155/2018/4135813] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2017] [Accepted: 03/04/2018] [Indexed: 01/19/2023] Open
Abstract
Objective Laparoscopic sleeve gastrectomy (LSG) was considered mainly as a restrictive procedure due to anatomic alterations in the upper gastrointestinal tract. Additionally, due to neurohormonal alterations, LSG modifies the gastrointestinal motility, which controls appetite and feeling of satiety. Aim The aim of the study was to review the impact of laparoscopic sleeve gastrectomy on gastrointestinal motility. Material and Methods A search of the medical literature was undertaken in Pubmed, Web of Science, and Cochrane library. Esophageal, gastric, bowel motility were assessed separately. Results Nine studies assessed esophageal motility. The data remain debatable attributing to the heterogeneity of follow-up timing, surgical technique, bougie size, and distance from pylorus. The stomach motility was assessed in eighteen studies. Functionally, the sleeve was divided into a passive sleeve and an accelerated antrum. All scintigraphic studies revealed accelerated gastric emptying after LSG except of one. Patients demonstrated a rapid gastroduodenal transit time. The resection of the gastric pacemaker had as a consequence aberrant distal ectopic pacemaking or bioelectrical quiescence after LSG. The bowel motility was the least studied. Small bowel transit time was reduced; opposite to that the initiation of cecal filling and the ileocecal valve transit was delayed. Conclusion Laparoscopic sleeve gastrectomy has impacts on gastrointestinal motility. The data remain debatable for esophageal motility. Stomach and small bowel motility were accelerated, while the initiation of cecal filling and the ileocecal valve transit was delayed. Further pathophysiological studies are needed to evaluate the correlation of motility data with clinical symptoms.
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Kiang JG, Anderson MN, Smith JT. Ghrelin therapy mitigates bone marrow injury and splenocytopenia by sustaining circulating G-CSF and KC increases after irradiation combined with wound. Cell Biosci 2018; 8:27. [PMID: 29632660 PMCID: PMC5887249 DOI: 10.1186/s13578-018-0225-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Accepted: 03/30/2018] [Indexed: 01/02/2023] Open
Abstract
Background Radiation injury combined wound (CI) enhances acute radiation syndrome and subsequently mortality as compared to radiation injury alone (RI). We previously reported that ghrelin (a 28-amino-acid-peptide secreted from the stomach) treatment significantly increased a 30-day survival, mitigated hematopoietic death, circulating white blood cell (WBC) depletion and splenocytopenia and accelerated skin-wound healing on day 30 after CI. Herein, we aimed to study the ghrelin efficacy at early time points after CI. Methods B6D2F1/J female mice were exposed to 60Co-γ-photon radiation at 9.5 Gy (LD50/30) followed by a 15% total-body-surface-area skin wound. Several endpoints were measured at 4-5 h, days 1, 3, 7 and 15. Results Histological analysis of sternums on day 15 showed that CI induced more adipocytes and less megakaryocytes than RI. Bone marrow cell counts from femurs also indicated CI resulted in lower bone marrow cell counts on days 1, 7 and 15 than RI. Ghrelin treatment mitigated these CI-induced adverse effects. RI and CI decreased WBCs within 4-5 h and continued to decrease to day 15. Ghrelin treatment mitigated decreases in CI mice, mainly from all types of WBCs, but not RBCs, hemoglobin levels and hematocrit values. Ghrelin mitigated the CI-induced thrombocytopenia and splenocytopenia. CI increased granulocyte-colony stimulating factor (G-CSF) and keratinocyte chemoattractant (KC) in blood and bone marrow. Ghrelin therapy was able to enhance and sustain the increases in serum on day 15, probably contributed by spleen and ileum, suggesting the correlation between G-CSF and KC increases and the neutropenia mitigation. Activated caspase-3 levels in bone marrow cells were significantly mitigated by ghrelin therapy on days 3 and 15. Conclusions Our novel results are the first to suggest that ghrelin therapy effectively decreases hematopoietic death and splenocytopenia by sustaining circulating G-CSF and KC increases after CI. These results demonstrate efficacy of ghrelin as a radio-mitigator/therapy agent for CI.
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Affiliation(s)
- Juliann G Kiang
- 1Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889 USA.,2Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814 USA.,3Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814 USA
| | - Marsha N Anderson
- 1Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889 USA
| | - Joan T Smith
- 1Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889 USA
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