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Zong X, Wang Y, Chen Y, Fang P, Zhang Y. Role of lactoferrin and its derived peptides in metabolic syndrome treatment. Front Endocrinol (Lausanne) 2025; 16:1562653. [PMID: 40313489 PMCID: PMC12043466 DOI: 10.3389/fendo.2025.1562653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Accepted: 03/31/2025] [Indexed: 05/03/2025] Open
Abstract
The prevalence of metabolic syndrome is increasing globally year by year, which has prompted researchers to actively seek and develop natural biotherapeutics to address this challenge. Lactoferrin (LF), as a multifunctional iron-binding natural transferrin, has garnered significant attention due to its potential role in regulating metabolism and the immune system. Recent studies show lactoferrin may influence lipid metabolism and glucose-insulin balance, and its levels are linked to body measurements. We systematically summarized the phenotypic and genotypic changes of LF in patients with metabolic syndrome, and the effect of exogenous LF on the treatment of metabolic syndrome. We also recapitulate LF can alleviate insulin resistance by inhibiting the NF-κB inflammatory pathway, activating the IRS/PI3K/Akt/Glut signaling pathway, and inhibiting the renin-angiotensin system to reduce the blood pressure, therefore improving the metabolic syndrome. This provides an important theoretical basis for the clinical application of LF in metabolic syndrome.
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Affiliation(s)
- Xicui Zong
- Laboratory Training Center, Nanjing University of Chinese Medicine Hanlin College, Taizhou, Jiangsu, China
| | - Yajing Wang
- Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou, China
| | - Yuqing Chen
- School of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China
| | - Penghua Fang
- The First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yi Zhang
- School of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China
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2
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Obayashi M, Kimura M, Haraguchi A, Gotanda M, Kitagawa T, Matsuno M, Sakao K, Hamanaka D, Kusakisako K, Kameda T, Ibrahim HR, Ikadai H, Miyata T. Bovine lactoferrin inhibits Plasmodium berghei growth by binding to heme. Sci Rep 2024; 14:20344. [PMID: 39223194 PMCID: PMC11369202 DOI: 10.1038/s41598-024-70840-6] [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: 06/07/2024] [Accepted: 08/21/2024] [Indexed: 09/04/2024] Open
Abstract
Bovine lactoferrin (bLF) is a 77 kDa glycoprotein that is abundant in bovine breast milk and exerts various bioactive functions, including antibacterial and antiviral functions. Few studies have explored bLF activity against parasites. We found that bLF affects hemozoin synthesis by binding to heme, inhibiting heme iron polymerization necessary for Plasmodium berghei ANKA survival in infected erythrocytes, and also binds to hemozoin, causing it to disassemble. In a challenge test, bLF administration inhibited the growth of murine malaria parasites compared to untreated group growth. To determine whether the iron content of bLF affects the inhibition of malaria growth, we tested bLFs containing different amounts of iron (apo-bLF, native-bLF, and holo-bLF), but found no significant difference in their effects. This indicated that the active sites were located within the bLFs themselves. Further studies showed that the C-lobe domain of bLF can inhibit hemozoin formation and the growth of P. berghei ANKA. Evaluation of pepsin degradation products of the C-lobe identified a 47-amino-acid section, C-1, as the smallest effective region that could inhibit hemozoin formation. This study highlights bLF's potential as a novel therapeutic agent against malaria, underscoring the importance of its non-iron-dependent bioactive sites in combating parasite growth.
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Affiliation(s)
- Momoka Obayashi
- Division of Molecular Functions of Food, Department of Biochemistry and Biotechnology, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan
| | - Momoko Kimura
- Division of Molecular Functions of Food, Department of Biochemistry and Biotechnology, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan
| | - Asako Haraguchi
- Laboratory of Veterinary Parasitology, School of Veterinary Medicine, Kitasato University, 23-35-1 Higashi, Towada, Aomori, 034-8628, Japan
| | - Mari Gotanda
- Division of Molecular Functions of Food, Department of Biochemistry and Biotechnology, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan
| | - Taiki Kitagawa
- Division of Molecular Functions of Food, Department of Biochemistry and Biotechnology, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan
| | - Misato Matsuno
- Division of Molecular Functions of Food, Department of Biochemistry and Biotechnology, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan
| | - Kozue Sakao
- The United Graduate School of Agricultural Sciences, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan
| | - Daisuke Hamanaka
- The United Graduate School of Agricultural Sciences, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan
| | - Kodai Kusakisako
- Laboratory of Veterinary Parasitology, School of Veterinary Medicine, Kitasato University, 23-35-1 Higashi, Towada, Aomori, 034-8628, Japan
| | - Tomoshi Kameda
- Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, 135-0064, Japan
| | - Hisham R Ibrahim
- Division of Molecular Functions of Food, Department of Biochemistry and Biotechnology, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan
- The United Graduate School of Agricultural Sciences, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan
| | - Hiromi Ikadai
- Laboratory of Veterinary Parasitology, School of Veterinary Medicine, Kitasato University, 23-35-1 Higashi, Towada, Aomori, 034-8628, Japan.
| | - Takeshi Miyata
- Division of Molecular Functions of Food, Department of Biochemistry and Biotechnology, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan.
- The United Graduate School of Agricultural Sciences, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan.
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Wazzan HA, Abraham AN, Saiara N, Anand S, Gill H, Shukla R. Effect of Milk Protein-Polyphenol Conjugate on the Regulation of GLP-1 Hormone. Foods 2024; 13:1935. [PMID: 38928876 PMCID: PMC11202982 DOI: 10.3390/foods13121935] [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: 05/27/2024] [Revised: 06/07/2024] [Accepted: 06/12/2024] [Indexed: 06/28/2024] Open
Abstract
Modern functional foods are designed to provide health benefits beyond basic nutrition. They are enriched with bioactive ingredients like probiotics, vitamins, minerals, and antioxidants. These foods support overall health, enhance immune function, and help prevent chronic diseases. Milk proteins and tea are known to influence satiety and regulate body weight. Studies have shown that green tea polyphenols, namely, (-)-epigallocatechin gallate (EGCG), and whey proteins, predominantly lactoferrin (LF) from milk, play a role in regulating satiety. This study aims to investigate the effect of conjugating EGCG with apo-lactoferrin (Apo-LF) and assessing these effects on satiety through monitoring glucagon-like peptide-1 (GLP-1) regulation in a human colon (NCI-H716) cell line. Apo-LF-EGCG conjugates were synthesized and characterized in terms of structural and functional properties. The effect on GLP-1 regulation was assessed by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) to monitor gene and protein expressions, respectively. The results revealed that the protein-polyphenol interaction occurs through the complex formation of hydrogen bonds at the O-H and carbonyl groups of EGCG. The conjugates also showed a significant up-regulation of gene and protein expression levels of GLP-1 while also preventing EGCG from degradation, thereby preserving its antioxidant properties. The Apo-LF-EGCG conjugates increase satiety via increasing GLP-1 secretion in human colon cells while simultaneously retaining the antioxidant properties of EGCG. Therefore, these conjugates show potential for use as dietary supplements to enhance satiety.
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Affiliation(s)
- Huda Abdulrahim Wazzan
- Food and Nutrition, School of Human Science and Design, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
- Bioscience and Food Technology, School of Science, RMIT University, Bundoora, VIC 3083, Australia;
| | - Amanda N. Abraham
- Sir Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory (NBRL), RMIT University, Melbourne, VIC 3001, Australia; (A.N.A.); (N.S.)
| | - Noshin Saiara
- Sir Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory (NBRL), RMIT University, Melbourne, VIC 3001, Australia; (A.N.A.); (N.S.)
| | - Sushil Anand
- Bioscience and Food Technology, School of Science, RMIT University, Bundoora, VIC 3083, Australia;
| | - Harsharn Gill
- Bioscience and Food Technology, School of Science, RMIT University, Bundoora, VIC 3083, Australia;
| | - Ravi Shukla
- Bioscience and Food Technology, School of Science, RMIT University, Bundoora, VIC 3083, Australia;
- Sir Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory (NBRL), RMIT University, Melbourne, VIC 3001, Australia; (A.N.A.); (N.S.)
- Centre for Advanced Materials & Industrial Chemistry, RMIT University, Melbourne, VIC 3001, Australia
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Pu TY, Chuang KC, Tung MC, Yen CC, Chen YH, Cidem A, Ko CH, Chen W, Chen CM. Lactoferrin as a therapeutic agent for attenuating hepatic stellate cell activation in thioacetamide-induced liver fibrosis. Biomed Pharmacother 2024; 174:116490. [PMID: 38554526 DOI: 10.1016/j.biopha.2024.116490] [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: 01/18/2024] [Revised: 03/16/2024] [Accepted: 03/19/2024] [Indexed: 04/01/2024] Open
Abstract
Liver fibrosis is a chronic liver disease caused by prolonged liver injuries. Excessive accumulation of extracellular matrix replaces the damaged hepatocytes, leading to fibrous scar formation and fibrosis induction. Lactoferrin (LF) is a glycoprotein with a conserved, monomeric signal polypeptide chain, exhibiting diverse physiological functions, including antioxidant, anti-inflammatory, antibacterial, antifungal, antiviral, and antitumoral activities. Previous study has shown LF's protective role against chemically-induced liver fibrosis in rats. However, the mechanisms of LF in liver fibrosis are still unclear. In this study, we investigated LF's mechanisms in thioacetamide (TAA)-induced liver fibrosis in rats and TGF-β1-treated HSC-T6 cells. Using ultrasonic imaging, H&E, Masson's, and Sirius Red staining, we demonstrated LF's ability to improve liver tissue damage and fibrosis induced by TAA. LF reduced the levels of ALT, AST, and hydroxyproline in TAA-treated liver tissues, while increasing catalase levels. Additionally, LF treatment decreased mRNA expression of inflammatory factors such as Il-1β and Icam-1, as well as fibrogenic factors including α-Sma, Collagen I, and Ctgf in TAA-treated liver tissues. Furthermore, LF reduced TAA-induced ROS production and cell death in FL83B cells, and decreased α-SMA, Collagen I, and p-Smad2/3 productions in TGF-β1-treated HSC-T6 cells. Our study highlights LF's ability to ameliorate TAA-induced hepatocyte damage, oxidative stress, and liver fibrosis in rats, potentially through its inhibitory effect on HSC activation. These findings suggest LF's potential as a therapeutic agent for protecting against liver injuries and fibrosis.
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Affiliation(s)
- Tzu-Yu Pu
- Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan
| | - Kai-Cheng Chuang
- Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan
| | - Min-Che Tung
- Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; Department of Surgery, Tungs' Taichung Metro Harbor Hospital, Taichung 435, Taiwan
| | - Chih-Ching Yen
- Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, China Medical University Hospital, and College of Health Care, China Medical University, Taichung 404, Taiwan
| | - Yu-Hsuan Chen
- Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan
| | - Abdulkadir Cidem
- Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; Department of Molecular Biology and Genetics, Erzurum Technical University, Erzurum 25250, Turkey
| | - Chu-Hsun Ko
- Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan
| | - Wei Chen
- Division of Pulmonary and Critical Care Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan
| | - Chuan-Mu Chen
- Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; The iEGG and Animal Biotechnology Center, and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan.
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Li B, Zhang B, Zhang F, Liu X, Zhang Y, Peng W, Teng D, Mao R, Yang N, Hao Y, Wang J. Interaction between Dietary Lactoferrin and Gut Microbiota in Host Health. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:7596-7606. [PMID: 38557058 DOI: 10.1021/acs.jafc.3c09050] [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: 04/04/2024]
Abstract
The gut microbiota are known to play an important role in host health and disease. Alterations in the gut microbiota composition can disrupt the stability of the gut ecosystem, which may result in noncommunicable chronic diseases (NCCDs). Remodeling the gut microbiota through personalized nutrition is a novel therapeutic avenue for both disease control and prevention. However, whether there are commonly used gut microbiota-targeted diets and how gut microbiota-diet interactions combat NCCDs and improve health remain questions to be addressed. Lactoferrin (LF), which is broadly used in dietary supplements, acts not only as an antimicrobial in the defense against enteropathogenic bacteria but also as a prebiotic to propagate certain probiotics. Thus, LF-induced gut microbiota alterations can be harnessed to induce changes in host physiology, and the underpinnings of their relationships and mechanisms are beginning to unravel in studies involving humans and animal models.
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Affiliation(s)
- Bing Li
- Institute of Translational Medicine, College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou 466001, Henan, PR China
| | - Bo Zhang
- International Joint Research Laboratory for Biomedical Nanomaterials of Henan, Zhoukou Normal University, Zhoukou 466001, Henan, PR China
| | - Fuli Zhang
- Institute of Translational Medicine, College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou 466001, Henan, PR China
| | - Xiaomeng Liu
- Institute of Translational Medicine, College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou 466001, Henan, PR China
| | - Yunxia Zhang
- Institute of Translational Medicine, College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou 466001, Henan, PR China
| | - Weifeng Peng
- Institute of Translational Medicine, College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou 466001, Henan, PR China
| | - Da Teng
- Gene Engineering Lab, Feed Research Institute, Chinese Academy of Agricultural Science, Beijing 100081, P. R. China
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing 100081, P. R. China
| | - Ruoyu Mao
- Gene Engineering Lab, Feed Research Institute, Chinese Academy of Agricultural Science, Beijing 100081, P. R. China
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing 100081, P. R. China
| | - Na Yang
- Gene Engineering Lab, Feed Research Institute, Chinese Academy of Agricultural Science, Beijing 100081, P. R. China
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing 100081, P. R. China
| | - Ya Hao
- Gene Engineering Lab, Feed Research Institute, Chinese Academy of Agricultural Science, Beijing 100081, P. R. China
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing 100081, P. R. China
| | - Jianhua Wang
- Gene Engineering Lab, Feed Research Institute, Chinese Academy of Agricultural Science, Beijing 100081, P. R. China
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing 100081, P. R. China
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Wang W, An Q, Huang K, Dai Y, Meng Q, Zhang Y. Unlocking the power of Lactoferrin: Exploring its role in early life and its preventive potential for adult chronic diseases. Food Res Int 2024; 182:114143. [PMID: 38519174 DOI: 10.1016/j.foodres.2024.114143] [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: 12/21/2023] [Revised: 02/05/2024] [Accepted: 02/17/2024] [Indexed: 03/24/2024]
Abstract
Nutrition during the early postnatal period exerts a profound impact on both infant development and later-life health. Breast milk, which contains lactoferrin, a dynamic protein, plays a crucial role in the growth of various biological systems and in preventing numerous chronic diseases. Based on the relationship between early infant development and chronic diseases later in life, this paper presents a review of the effects of lactoferrin in early life on neonates intestinal tract, immune system, nervous system, adipocyte development, and early intestinal microflora establishment, as well as the preventive and potential mechanisms of early postnatal lactoferrin against adult allergy, inflammatory bowel disease, depression, cancer, and obesity. Furthermore, we summarized the application status of lactoferrin in the early postnatal period and suggested directions for future research.
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Affiliation(s)
- Wenli Wang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Qin An
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Kunlun Huang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Yunping Dai
- College of Biological Sciences, China Agricultural University, Beijing, China
| | - Qingyong Meng
- College of Biological Sciences, China Agricultural University, Beijing, China
| | - Yali Zhang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.
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Mohandas S, Milan KL, Anuradha M, Ramkumar KM. Exploring Lactoferrin as a novel marker for disease pathology and ferroptosis regulation in gestational diabetes. J Reprod Immunol 2024; 161:104182. [PMID: 38159430 DOI: 10.1016/j.jri.2023.104182] [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: 10/15/2023] [Revised: 11/30/2023] [Accepted: 12/12/2023] [Indexed: 01/03/2024]
Abstract
Iron overload is linked to heightened susceptibility to ferroptosis, a process increasingly implicated in diabetes pathogenesis. This present study aims to assess the utility of Lactoferrin in predicting different stages of GDM and explore its association with disease pathology and ferroptosis. In this observational study, 72 pregnant women were recruited and categorized into three groups: healthy pregnant women without diabetes (NGDM, n = 24), early gestational diabetes (eGDM, n = 24), and established gestational diabetes (GDM, n = 24), all receiving standard antenatal care at 12 weeks of gestation. Circulating levels of ferritin, soluble transferrin receptor (sTFR), and Lactoferrin using multiplexed bead-based cytokine immunoassay. Gene expression analysis focused on analyzing crucial ferroptosis regulators, SLC7A11 and GPX4, in isolated peripheral blood mononuclear cells (PBMCs). A significant elevation in ferritin levels and a decrease in the sTFR: Ferritin ratio supported iron overload and disrupted iron homeostasis in GDM subjects. Notably, Lactoferrin levels were significantly lower in women with GDM than in the control group and those with eGDM. This decline in Lactoferrin correlated with increased hyperglycemia indicators and reduced expression of ferroptosis regulators among GDM patients. Furthermore ROC curve analysis demonstrated that Lactoferrin shows promise as a valuable marker for distinguishing individuals with GDM from those with eGDM. Lactoferrin shows promise as a biomarker for detecting GDM. These findings indicate its role as a potential biomarker and highlight Lactoferrin as a critical regulator of hyperglycemia and ferroptosis in women with GDM.
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Affiliation(s)
- Sundhar Mohandas
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, Tamil Nadu, India
| | - Kunnath Lakshmanan Milan
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, Tamil Nadu, India
| | - Murugesan Anuradha
- Department of Obstetrics & Gynecology, SRM Medical College Hospital and Research Centre, Kattankulathur 603203, Tamil Nadu, India
| | - Kunka Mohanram Ramkumar
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, Tamil Nadu, India.
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Ianiro G, Niro A, Rosa L, Valenti P, Musci G, Cutone A. To Boost or to Reset: The Role of Lactoferrin in Energy Metabolism. Int J Mol Sci 2023; 24:15925. [PMID: 37958908 PMCID: PMC10650157 DOI: 10.3390/ijms242115925] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 10/25/2023] [Accepted: 10/31/2023] [Indexed: 11/15/2023] Open
Abstract
Many pathological conditions, including obesity, diabetes, hypertension, heart disease, and cancer, are associated with abnormal metabolic states. The progressive loss of metabolic control is commonly characterized by insulin resistance, atherogenic dyslipidemia, inflammation, central obesity, and hypertension, a cluster of metabolic dysregulations usually referred to as the "metabolic syndrome". Recently, nutraceuticals have gained attention for the generalized perception that natural substances may be synonymous with health and balance, thus becoming favorable candidates for the adjuvant treatment of metabolic dysregulations. Among nutraceutical proteins, lactoferrin (Lf), an iron-binding glycoprotein of the innate immune system, has been widely recognized for its multifaceted activities and high tolerance. As this review shows, Lf can exert a dual role in human metabolism, either boosting or resetting it under physiological and pathological conditions, respectively. Lf consumption is safe and is associated with several benefits for human health, including the promotion of oral and gastrointestinal homeostasis, control of glucose and lipid metabolism, reduction of systemic inflammation, and regulation of iron absorption and balance. Overall, Lf can be recommended as a promising natural, completely non-toxic adjuvant for application as a long-term prophylaxis in the therapy for metabolic disorders, such as insulin resistance/type II diabetes and the metabolic syndrome.
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Affiliation(s)
- Giusi Ianiro
- Department of Biosciences and Territory, University of Molise, 86090 Pesche, Italy; (G.I.); (A.N.); (G.M.)
| | - Antonella Niro
- Department of Biosciences and Territory, University of Molise, 86090 Pesche, Italy; (G.I.); (A.N.); (G.M.)
| | - Luigi Rosa
- Department of Public Health and Infectious Diseases, University of Rome La Sapienza, 00185 Rome, Italy; (L.R.); (P.V.)
| | - Piera Valenti
- Department of Public Health and Infectious Diseases, University of Rome La Sapienza, 00185 Rome, Italy; (L.R.); (P.V.)
| | - Giovanni Musci
- Department of Biosciences and Territory, University of Molise, 86090 Pesche, Italy; (G.I.); (A.N.); (G.M.)
| | - Antimo Cutone
- Department of Biosciences and Territory, University of Molise, 86090 Pesche, Italy; (G.I.); (A.N.); (G.M.)
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Nilaweera KN, Cotter PD. Can dietary proteins selectively reduce either the visceral or subcutaneous adipose tissues? Obes Rev 2023; 24:e13613. [PMID: 37548066 DOI: 10.1111/obr.13613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 06/22/2023] [Accepted: 07/12/2023] [Indexed: 08/08/2023]
Abstract
There is a considerable appeal for interventions that can selectively reduce either the visceral or subcutaneous white adipose tissues in humans and other species because of their associated impact on outcomes related to metabolic health. Here, we reviewed the data related to the specificity of five interventions to affect the two depots in humans and rodents. The interventions relate to the use of dietary proteins, monounsaturated fatty acids, polyunsaturated fatty acids, calorie restriction, or bariatric surgery. The available data show that calorie restriction and bariatric surgery reduce both visceral and subcutaneous tissues, whereas there is no consistency in the effect of monounsaturated or polyunsaturated fatty acids. Dietary proteins, more specifically, whey proteins show efficacy to reduce one or both depots based on how the proteins interact with other macronutrients in the diet. We provide evidence that this specificity is related to changes in the composition and the functional potential of the gut microbiota and the resulting metabolites produced by these microorganisms. The effect of the sex of the host is also discussed. This knowledge may help to develop nutritional approaches to deplete either the visceral or subcutaneous adipose tissues and improve metabolic health in humans and other species.
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Affiliation(s)
- Kanishka N Nilaweera
- Food Biosciences Department, Teagasc Food Research Centre, Fermoy, County Cork, Ireland
- VistaMilk Research Centre, Teagasc, Fermoy, County Cork, Ireland
| | - Paul D Cotter
- Food Biosciences Department, Teagasc Food Research Centre, Fermoy, County Cork, Ireland
- VistaMilk Research Centre, Teagasc, Fermoy, County Cork, Ireland
- APC Microbiome Ireland, University College Cork, Cork, Ireland
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Coccolini C, Berselli E, Blanco-Llamero C, Fathi F, Oliveira MBPP, Krambeck K, Souto EB. Biomedical and Nutritional Applications of Lactoferrin. Int J Pept Res Ther 2023; 29:71. [DOI: 10.1007/s10989-023-10541-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/06/2023] [Indexed: 01/05/2025]
Abstract
AbstractLactoferrin (Lf) is a glycoprotein belonging to the transferrin family, which can be found in mammalian milk. It was first isolated from bovine milk in the 1930s, and later in the 1960s, it was determined from human milk. This multifunctional protein has the specific ability to bind iron. It plays various biological roles, such as antibacterial, antiviral, antifungal, anti-tumour, anti-obesity, antioxidant, anti-inflammatory and immunomodulatory activities. There are several studies describing its use against in various cancer cell lines (e.g., liver, lung and breast) and the glycoprotein has even been reported to inhibit the development of experimental metastases in mice. Previous studies also suggest Lf-mediated neuroprotection against age-related neurodegenerative diseases and it is also expected to attenuate aging. More recently, Lf has been proposed as a potential approach in COVID-19 prophylaxis. In this review, we discuss the recent developments about the biological activities of this pleiotropic glycoprotein that will reason the exploitation of its biomedical and supplementary nutritional value.
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Yokoyama K, Takamura M, Watanabe J, Nakamura A, Sato Y, Sekine A, Terai S. The Visceral-to-subcutaneous Adipose Tissue Area Ratio Is Associated with Retreatment in Chronic Pancreatitis Patients with Pancreatolithiasis after Extracorporeal Shock Wave Lithotripsy. Intern Med 2022; 61:3633-3639. [PMID: 35650122 PMCID: PMC9841102 DOI: 10.2169/internalmedicine.9038-21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Objective Extracorporeal shock wave lithotripsy (ESWL) has been used to treat pancreatolithiasis in patients with chronic pancreatitis (CP), but the high recurrence rate remains challenging. We therefore evaluated the association between body composition parameters and the prediction of retreatment after ESWL. Methods This study retrospectively evaluated 42 patients with CP who had been treated with ESWL between 2008 and 2019 in a single center. Body composition parameters were measured on pretreatment computed tomography images. Patients who underwent repeat ESWL were classified as the retreatment group. Results There were 13 (31.0%) and 29 (69.0%) patients in the retreatment and non-retreatment groups, respectively. The visceral-to-subcutaneous adipose tissue area ratio (VSR) of the retreatment group was significantly lower than that of the non-retreatment group (p=0.016). When divided by the median VSR, 10 of the 20 patients with a VSR of <0.85 underwent retreatment, whereas 3 of the 22 patients with a VSR of ≥0.85 underwent retreatment (p=0.019). According to a multivariate analysis, the VSR (p=0.010) and age (p=0.037) were independent factors associated with retreatment after ESWL. Conclusion This study showed that the VSR can predict the retreatment of patients with CP after ESWL.
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Affiliation(s)
- Kunihiko Yokoyama
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Science, Japan
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Science, Japan
- Department of Gastroenterology, JA Niigata Kouseiren Nagaoka Chuo General Hospital, Japan
| | - Jun Watanabe
- Department of Internal Medicine, Niigata Prefectural Yoshida Hospital, Japan
| | - Atsuo Nakamura
- Department of Internal Medicine, Niigata Prefectural Yoshida Hospital, Japan
| | - Yuichi Sato
- Department of Gastroenterology, JA Niigata Kouseiren Nagaoka Chuo General Hospital, Japan
| | - Atsuo Sekine
- Department of Internal Medicine, Niigata Prefectural Yoshida Hospital, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Science, Japan
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12
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Otsuki K, Nishi T, Kondo T, Okubo K. Review, role of lactoferrin in preventing preterm delivery. Biometals 2022; 36:521-530. [PMID: 36495415 PMCID: PMC10182139 DOI: 10.1007/s10534-022-00471-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 11/17/2022] [Indexed: 12/14/2022]
Abstract
AbstractPrevention of preterm birth (PTB) is a global challenge and is one of the most important issues to be addressed in perinatal care. The hypothesis that ascending lower genital infection leads to PTB has been tested in numerous in vitro and in vivo studies. For patients with intractable vaginitis or high-risk patients with successive PTBs, mainly due to intra-uterine infection, the vaginal flora is enhanced to increase systemic immunity and locally propagate Lactobacillus species. It has been shown that the administration of lactoferrin (LF), a prebiotic with minimum side effects, may be effective in suppressing PTB. This hypothesis has been evaluated in this review using various relevant test examples. The findings suggest that LF may play a role in inflammatory protection in pregnant human cervical tissue. The antibacterial and anti-cytokine effects of LF in human-derived mucus-producing cervical cell lines were also demonstrated. It was also clarified that LF suppresses PTB and improves the prognosis of pups in inflammation-induced PTB animal models. Thus, we have identified that LF, a prebiotic contained in breast milk, can be clinically applied to suppress PTB in humans and to prevent PTBs in high-risk pregnancies.
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Affiliation(s)
- Katsufumi Otsuki
- Department of Obstetrics and Gynecology, Showa University Koto Toyosu Hospital, 5-1-38 Toyosu, Koto-Ku, Tokyo, 135-8577, Japan.
| | - Takshi Nishi
- Department of Obstetrics and Gynecology, Showa University Koto Toyosu Hospital, 5-1-38 Toyosu, Koto-Ku, Tokyo, 135-8577, Japan
| | - Tetsuro Kondo
- Department of Obstetrics and Gynecology, Showa University Koto Toyosu Hospital, 5-1-38 Toyosu, Koto-Ku, Tokyo, 135-8577, Japan
| | - Kazutoshi Okubo
- Department of Obstetrics and Gynecology, Showa University Koto Toyosu Hospital, 5-1-38 Toyosu, Koto-Ku, Tokyo, 135-8577, Japan
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13
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Hassan MA, Abedelmaksoud TG, Abd El-Maksoud AA. Effects of Lactoferrin Supplemented with Fermented Milk on Obesity-Associated Pancreatic Damage in Rats. LIFE (BASEL, SWITZERLAND) 2022; 12:life12122019. [PMID: 36556384 PMCID: PMC9785828 DOI: 10.3390/life12122019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 11/26/2022] [Accepted: 11/30/2022] [Indexed: 12/09/2022]
Abstract
Non-alcoholic fatty pancreas disease is a newly emerging disease that represents an important risk factor for the development of pancreatic cancer. Obesity is a risk factor for pancreatic diseases, including pancreatitis and pancreatic cancer. On the other hand, the development of healthy aspects-based food products is a recent trend. Lactoferrin is a component of the body's immune system, which interacts with DNA, RNA, polysaccharides, and heparin, and it has many biological functions and many important immunomodulatory properties. Thus, this study aims to investigate the enhancement effect of supplementation of lactoferrin with stirred yogurt on weight gain, lipid profile, glucose level, and pancreatic enzymes in animals fed a high-fat diet (HFD). Forty-eight female albino rats were divided into 6 groups treated orally for 45 days as follows: negative control (basal diet), positive control (add 1% cholesterol), stirred yogurt (SY), Lactoferrin LF (100 mg/kg bw), supplementation of lactoferrin with stirred yogurt SY-LF at two concentrations LF1 (50 mg/kg bw) and LF2 (100 mg/kg bw). Blood and pancreas samples were collected for different analyses. Animals fed with a HFD showed a significant increase in body weight, total cholesterol, triglyceride, low-density lipoprotein (LDL), glucose level, amylase, and Lipase enzymes (44.72%, 151.33 mg/dL, 142.67 mg/dL, 85.37 mg/dL, 141.33 mg/dL, 39.33 U/mL, 23.43 U/mL). Moreover, it observed a significant decrease in high-density lipoprotein (HDL, 37.33 mg/dL); meanwhile, SY fortified with lactoferrin was useful in losing weight gain and improving lipid profile, pancreas function, and histological change in the pancreas. The supplementation of lactoferrin at 100 mg/Kg bw with LB. Acidophilus as a probiotic was more effective for pancreas functions. This application is a natural protective alternative to manufactured medicines for children and the elderly as a natural product.
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Affiliation(s)
- Mona A. Hassan
- Food Evaluation and Food Science Department, National Organization for Drug Control and Research, Giza 12553, Egypt
| | | | - Ahmed A. Abd El-Maksoud
- Dairy Science Department, Faculty of Agriculture, Cairo University, Giza 12613, Egypt
- Correspondence:
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14
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Mayneris-Perxachs J, Moreno-Navarrete JM, Fernández-Real JM. The role of iron in host-microbiota crosstalk and its effects on systemic glucose metabolism. Nat Rev Endocrinol 2022; 18:683-698. [PMID: 35986176 DOI: 10.1038/s41574-022-00721-3] [Citation(s) in RCA: 70] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/01/2022] [Indexed: 11/09/2022]
Abstract
Iron is critical for the appearance and maintenance of life on Earth. Almost all organisms compete or cooperate for iron acquisition, demonstrating the importance of this essential element for the biological and physiological processes that are key for the preservation of metabolic homeostasis. In humans and other mammals, the bidirectional interactions between the bacterial component of the gut microbiota and the host for iron acquisition shape both host and microbiota metabolism. Bacterial functions influence host iron absorption, whereas the intake of iron, iron deficiency and iron excess in the host affect bacterial biodiversity, taxonomy and function, resulting in changes in bacterial virulence. These consequences of the host-microbial crosstalk affect systemic levels of iron, its storage in different tissues and host glucose metabolism. At the interface between the host and the microbiota, alterations in the host innate immune system and in circulating soluble factors that regulate iron (that is, hepcidin, lipocalin 2 and lactoferrin) are associated with metabolic disease. In fact, patients with obesity-associated metabolic dysfunction and insulin resistance exhibit dysregulation in iron homeostasis and alterations in their gut microbiota profile. From an evolutionary point of view, the pursuit of two important nutrients - glucose and iron - has probably driven human evolution towards the most efficient pathways and genes for human survival and health.
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Affiliation(s)
- Jordi Mayneris-Perxachs
- Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IDIBGI), Girona, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
| | - José María Moreno-Navarrete
- Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IDIBGI), Girona, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
| | - José Manuel Fernández-Real
- Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IDIBGI), Girona, Spain.
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.
- Department of Medicine, Universitat de Girona, Girona, Spain.
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15
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Xu SF, Pang ZQ, Fan YG, Zhang YH, Meng YH, Bai CY, Jia MY, Chen YH, Wang ZY, Guo C. Astrocyte-specific loss of lactoferrin influences neuronal structure and function by interfering with cholesterol synthesis. Glia 2022; 70:2392-2408. [PMID: 35946355 DOI: 10.1002/glia.24259] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 07/26/2022] [Accepted: 07/29/2022] [Indexed: 11/07/2022]
Abstract
Growing evidence indicates that circulating lactoferrin (Lf) is implicated in peripheral cholesterol metabolism disorders. It has emerged that the distribution of Lf changes in astrocytes of aging brains and those exhibiting neurodegeneration; however, its physiological and/or pathological role remains unknown. Here, we demonstrate that astrocyte-specific knockout of Lf (designated cKO) led to decreased body weight and cognitive abnormalities during early life in mice. Accordingly, there was a reduction in neuronal outgrowth and synaptic structure in cKO mice. Importantly, Lf deficiency in the primary astrocytes led to decreased sterol regulatory element binding protein 2 (Srebp2) activation and cholesterol production, and cholesterol content in cKO mice and/or in astrocytes was restored by exogenous Lf or a Srebp2 agonist. Moreover, neuronal dendritic complexity and total dendritic length were decreased after culture with the culture medium of the primary astrocytes derived from cKO mice and that this decrease was reversed after cholesterol supplementation. Alternatively, these alterations were associated with an activation of AMP-activated protein kinase (AMPK) and inhibition of SREBP2 nuclear translocation. These data suggest that astrocytic Lf might directly or indirectly control in situ cholesterol synthesis, which may be implicated in neurodevelopment and several neurological diseases.
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Affiliation(s)
- Shuang-Feng Xu
- College of Life and Health Sciences, Institute of Neuroscience, Northeastern University, Shenyang, China
| | - Zhong-Qiu Pang
- College of Life and Health Sciences, Institute of Neuroscience, Northeastern University, Shenyang, China
| | - Yong-Gang Fan
- College of Life and Health Sciences, Institute of Neuroscience, Northeastern University, Shenyang, China
- Health Sciences Institute, Key Laboratory of Major Chronic Diseases of Nervous System, China Medical University, Shenyang, China
| | - Yan-Hui Zhang
- College of Life and Health Sciences, Institute of Neuroscience, Northeastern University, Shenyang, China
- Health Sciences Institute, Key Laboratory of Major Chronic Diseases of Nervous System, China Medical University, Shenyang, China
| | - Yu-Han Meng
- College of Life and Health Sciences, Institute of Neuroscience, Northeastern University, Shenyang, China
| | - Chen-Yang Bai
- College of Life and Health Sciences, Institute of Neuroscience, Northeastern University, Shenyang, China
| | - Meng-Yu Jia
- College of Life and Health Sciences, Institute of Neuroscience, Northeastern University, Shenyang, China
| | - Yan-Hong Chen
- College of Life and Health Sciences, Institute of Neuroscience, Northeastern University, Shenyang, China
| | - Zhan-You Wang
- Health Sciences Institute, Key Laboratory of Major Chronic Diseases of Nervous System, China Medical University, Shenyang, China
| | - Chuang Guo
- College of Life and Health Sciences, Institute of Neuroscience, Northeastern University, Shenyang, China
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16
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Matsuoka R, Sugano M. Health Functions of Egg Protein. Foods 2022; 11:2309. [PMID: 35954074 PMCID: PMC9368041 DOI: 10.3390/foods11152309] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 07/22/2022] [Accepted: 07/29/2022] [Indexed: 11/16/2022] Open
Abstract
Egg protein is a remarkably abundant source of protein, with an amino acid score of 100 and the highest net protein utilization rate. However, there have been relatively fewer studies investigating the health benefits of egg protein. In this review, we have summarized the available information regarding the health benefits of egg proteins based on human studies. In particular, studies conducted on the characteristics of egg whites, as they are high in pure protein, have reported their various health functions, such as increases in muscle mass and strength enhancement, lowering of cholesterol, and visceral fat reduction. Moreover, to facilitate and encourage the use of egg white protein in future, we also discuss its health functions. These benefits were determined by developing an egg white hydrolysate and lactic-fermented egg whites, with the latter treatment simultaneously improving the egg flavor. The health benefits of the protein hydrolysates from the egg yolk (bone growth effect) and eggshell membrane (knee join pain-lowering effect) have been limited in animal studies. Therefore, the consumption of egg protein may contribute to the prevention of physical frailty and metabolic syndromes.
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Affiliation(s)
| | - Michihiro Sugano
- Kyushu University, Fukuoka 819-0395, Japan;
- Prefectural University of Kumamoto, Kumamoto 862-8502, Japan
- Chair of the Japan Egg Science Society, Tokyo 182-0002, Japan
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17
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Li YQ, Guo C. A Review on Lactoferrin and Central Nervous System Diseases. Cells 2021; 10:cells10071810. [PMID: 34359979 PMCID: PMC8307123 DOI: 10.3390/cells10071810] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 07/08/2021] [Accepted: 07/15/2021] [Indexed: 12/14/2022] Open
Abstract
Central nervous system (CNS) diseases are currently one of the major health issues around the world. Most CNS disorders are characterized by high oxidative stress levels and intense inflammatory responses in affected tissues. Lactoferrin (Lf), a multifunctional iron-binding glycoprotein, plays a significant role in anti-inflammatory, antibacterial, antiviral, reactive oxygen species (ROS) modulator, antitumor immunity, and anti-apoptotic processes. Previous studies have shown that Lf is abnormally expressed in a variety of neurological diseases, especially neurodegenerative diseases. Recently, the promotion of neurodevelopment and neuroprotection by Lf has attracted widespread attention, and Lf could be exploited both as an active therapeutic agent and drug nanocarrier. However, our understanding of the roles of Lf proteins in the initiation or progression of CNS diseases is limited, especially the roles of Lf in regulating neurogenesis. This review highlights recent advances in the understanding of the major pharmacological effects of Lf in CNS diseases, including neurodegenerative diseases, cerebrovascular disease, developmental delays in children, and brain tumors.
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Affiliation(s)
| | - Chuang Guo
- Correspondence: ; Tel.: +86-24-8365-6109
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18
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Interaction of Lactoferrin with Unsaturated Fatty Acids: In Vitro and In Vivo Study of Human Lactoferrin/Oleic Acid Complex Cytotoxicity. MATERIALS 2021; 14:ma14071602. [PMID: 33805987 PMCID: PMC8037541 DOI: 10.3390/ma14071602] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 03/16/2021] [Accepted: 03/21/2021] [Indexed: 12/24/2022]
Abstract
As shown recently, oleic acid (OA) in complex with lactoferrin (LF) causes the death of cancer cells, but no mechanism(s) of that toxicity have been disclosed. In this study, constitutive parameters of the antitumor effect of LF/OA complex were explored. Complex LF/OA was prepared by titrating recombinant human LF with OA. Spectral analysis was used to assess possible structural changes of LF within its complex with OA. Structural features of apo-LF did not change within the complex LF:OA = 1:8, which was toxic for hepatoma 22a cells. Cytotoxicity of the complex LF:OA = 1:8 was tested in cultured hepatoma 22a cells and in fresh erythrocytes. Its anticancer activity was tested in mice carrying hepatoma 22a. In mice injected daily with LF-8OA, the same tumor grew significantly slower. In 20% of animals, the tumors completely resolved. LF alone was less efficient, i.e., the tumor growth index was 0.14 for LF-8OA and 0.63 for LF as compared with 1.0 in the control animals. The results of testing from 48 days after the tumor inoculation showed that the survival rate among LF-8OA-treated animals was 70%, contrary to 0% rate in the control group and among the LF-treated mice. Our data allow us to regard the complex of LF and OA as a promising tool for cancer treatment.
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19
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Vasilyev V, Sokolov A, Kostevich V, Elizarova A, Gorbunov N, Panasenko O. Binding of lactoferrin to the surface of low-density lipoproteins modified by myeloperoxidase prevents intracellular cholesterol accumulation by human blood monocytes. Biochem Cell Biol 2021; 99:109-116. [DOI: 10.1139/bcb-2020-0141] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Myeloperoxidase (MPO) is a unique heme-containing peroxidase that can catalyze the formation of hypochlorous acid (HOCl). The strong interaction of MPO with low-density lipoproteins (LDL) promotes proatherogenic modification of LDL by HOCl. The MPO-modified LDL (Mox-LDL) accumulate in macrophages, resulting in the formation of foam cells, which is the pathognomonic symptom of atherosclerosis. A promising approach to prophylaxis and atherosclerosis therapy is searching for remedies that prevent the modification or accumulation of LDL in macrophages. Lactoferrin (LF) has several application points in obesity pathogenesis. We aimed to study LF binding to Mox-LDL and their accumulation in monocytes transformed into macrophages. Using surface plasmon resonance and ELISA techniques, we observed no LF interaction with intact LDL, whereas Mox-LDL strongly interacted with LF. The affinity of Mox-LDL to LF increased with the degree of oxidative modification of LDL. Moreover, an excess of MPO did not prevent interaction of Mox-LDL with LF. LF inhibits accumulation of cholesterol in macrophages exposed to Mox-LDL. The results obtained reinforce the notion of LF potency as a remedy against atherosclerosis.
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Affiliation(s)
- V.B. Vasilyev
- FSBSI (Institute of Experimental Medicine), Saint Petersburg 197376, Russia
- Saint Petersburg State University, Saint Petersburg 199034, Russia
| | - A.V. Sokolov
- FSBSI (Institute of Experimental Medicine), Saint Petersburg 197376, Russia
- Saint Petersburg State University, Saint Petersburg 199034, Russia
- Federal Research and Clinical Center of Physical–Chemical Medicine of Federal Medical Biological Agency, Moscow 119435, Russia
| | - V.A. Kostevich
- FSBSI (Institute of Experimental Medicine), Saint Petersburg 197376, Russia
- Federal Research and Clinical Center of Physical–Chemical Medicine of Federal Medical Biological Agency, Moscow 119435, Russia
| | - A.Yu. Elizarova
- FSBSI (Institute of Experimental Medicine), Saint Petersburg 197376, Russia
| | - N.P. Gorbunov
- FSBSI (Institute of Experimental Medicine), Saint Petersburg 197376, Russia
- Federal Research and Clinical Center of Physical–Chemical Medicine of Federal Medical Biological Agency, Moscow 119435, Russia
| | - O.M. Panasenko
- Federal Research and Clinical Center of Physical–Chemical Medicine of Federal Medical Biological Agency, Moscow 119435, Russia
- Pirogov Russian National Research Medical University, Moscow 117997, Russia
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20
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Rao VN, Fudim M, Mentz RJ, Michos ED, Felker GM. Regional adiposity and heart failure with preserved ejection fraction. Eur J Heart Fail 2020; 22:1540-1550. [PMID: 32619081 PMCID: PMC9991865 DOI: 10.1002/ejhf.1956] [Citation(s) in RCA: 91] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 06/28/2020] [Accepted: 06/30/2020] [Indexed: 12/12/2022] Open
Abstract
The role of obesity in the pathogenesis of heart failure (HF), and in particular HF with preserved ejection fraction (HFpEF), has drawn significant attention in recent years. The prevalence of both obesity and HFpEF has increased worldwide over the past decades and when present concomitantly suggests an obese-HFpEF phenotype. Anthropometrics, including body mass index, waist circumference, and waist-to-hip ratio, are associated with incident HFpEF. However, the cardiovascular effects of obesity may actually be driven by the distribution of fat, which can accumulate in the epicardial, visceral, and subcutaneous compartments. Regional fat can be quantified using non-invasive imaging techniques, including computed tomography, magnetic resonance imaging, and dual-energy X-ray absorptiometry. Regional variations in fat accumulation are associated with different HFpEF risk profiles, whereby higher epicardial and visceral fat have a much stronger association with HFpEF risk compared with elevated subcutaneous fat. Thus, regional adiposity may serve a pivotal role in the pathophysiology of HFpEF contributing to decreased cardiopulmonary fitness, impaired left ventricular compliance, upregulation of local and systemic inflammation, promotion of neurohormonal dysregulation, and increased intra-abdominal pressure and vascular congestion. Strategies to reduce total and regional adiposity have shown promise, including intensive exercise, dieting, and bariatric surgery programmes, but few studies have focused on HFpEF-related outcomes among obese. Further understanding the role these variable fat depots play in the progression of HFpEF and HFpEF-related hospitalizations may provide therapeutic targets in treating the obese-HFpEF phenotype.
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Affiliation(s)
- Vishal N Rao
- Division of Cardiology, Duke University School of Medicine, Durham, NC, USA
| | - Marat Fudim
- Division of Cardiology, Duke University School of Medicine, Durham, NC, USA
| | - Robert J Mentz
- Division of Cardiology, Duke University School of Medicine, Durham, NC, USA
| | - Erin D Michos
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - G Michael Felker
- Division of Cardiology, Duke University School of Medicine, Durham, NC, USA
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21
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Superti F. Lactoferrin from Bovine Milk: A Protective Companion for Life. Nutrients 2020; 12:nu12092562. [PMID: 32847014 PMCID: PMC7551115 DOI: 10.3390/nu12092562] [Citation(s) in RCA: 99] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 08/19/2020] [Accepted: 08/20/2020] [Indexed: 02/06/2023] Open
Abstract
Lactoferrin (Lf), an iron-binding multifunctional glycoprotein belonging to the transferrin family, is present in most biological secretions and reaches particularly high concentrations in colostrum and breast milk. A key function of lactoferrin is non-immune defence and it is considered to be a mediator linking innate and adaptive immune responses. Lf from bovine milk (bLf), the main Lf used in human medicine because of its easy availability, has been designated by the United States Food and Drug Administration as a food additive that is generally recognized as safe (GRAS). Among the numerous protective activities exercised by this nutraceutical protein, the most important ones demonstrated after its oral administration are: Antianemic, anti-inflammatory, antimicrobial, immunomodulatory, antioxidant and anticancer activities. All these activities underline the significance in host defence of bLf, which represents an ideal nutraceutical product both for its economic production and for its tolerance after ingestion. The purpose of this review is to summarize the most important beneficial activities demonstrated following the oral administration of bLf, trying to identify potential perspectives on its prophylactic and therapeutic applications in the future.
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Affiliation(s)
- Fabiana Superti
- National Centre for Innovative Technologies in Public Health, National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy
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Guo C, Xue H, Guo T, Zhang W, Xuan WQ, Ren YT, Wang D, Chen YH, Meng YH, Gao HL, Zhao P. Recombinant human lactoferrin attenuates the progression of hepatosteatosis and hepatocellular death by regulating iron and lipid homeostasis in ob/ob mice. Food Funct 2020; 11:7183-7196. [PMID: 32756704 DOI: 10.1039/d0fo00910e] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Lactoferrin (Lf), an iron-binding glycoprotein, has been shown to possess antioxidant and anti-inflammatory properties and exert modulatory effects on lipid homeostasis and non-alcoholic fatty liver disease (NAFLD), but our understanding of its regulatory mechanisms is limited and inconsistent. We used leptin-deficient (ob/ob) mice as the rodent model of NAFLD, and administered recombinant human Lf (4 mg per kg body weight) or control vehicle by intraperitoneal injection to evaluate the hepatoprotective effects of Lf. After 40 days of treatment with Lf, insulin sensitivity and hepatic steatosis in ob/ob mice were significantly improved with the down-regulation of sterol regulatory element binding protein-2 (SREBP2), indicating an improvement in hepatic lipid metabolism and function. We further explored the mechanism, and found that Lf may increase the hepatocellular iron output by targeting the hepcidin-ferroportin (FPn) axis, and then maintains the liver oxidative balance through a nonenzymatic antioxidant system, ultimately suppressing the death of hepatocytes. In addition, the cytoprotective role of Lf may be associated with the inhibition of endoplasmic reticulum (ER) stress and inflammation, promotion of autophagy of damaged hepatocytes and induction of up-regulation of hypoxia inducible factor-1α/vascular endothelial growth factor (HIF-lα/VEGF) to facilitate liver function recovery. These findings suggest that recombinant human Lf might be a potential therapeutic agent for mitigating or delaying the pathological process of NAFLD.
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Affiliation(s)
- Chuang Guo
- College of Life and Health Sciences, Northeastern University, No. 195, Chuangxin Road, Hunnan District, Shenyang, 110169, China.
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YALÇIN E, RAKICIOĞLU N. Biyoaktif Besin Peptitleri ve Sağlık Üzerine Etkileri. DÜZCE ÜNIVERSITESI SAĞLIK BILIMLERI ENSTITÜSÜ DERGISI 2020. [DOI: 10.33631/duzcesbed.559968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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Nagai M, Kubo M, Ando R, Ikeda M, Iwamoto H, Takeda Y, Nomoto M. Comparative examination of levodopa pharmacokinetics during simultaneous administration with lactoferrin in healthy subjects and the relationship between lipids and COMT inhibitory activity in vitro. Nutr Neurosci 2020; 25:462-471. [PMID: 32441567 DOI: 10.1080/1028415x.2020.1760532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Background: Lactoferrin (bLF) is an iron-binding multifunctional protein that is abundant in milk. In mice, it inhibits catechol-O-methyltransferase (COMT) activity and increases blood levodopa levels. However, the clinical effects are unknown.Objective: The objective of this study was to determine the effect of bLF on the kinetics of levodopa in blood.Design: The effects of the concomitant administration of a combined formulation of levodopa and an aromatic amino acid decarboxylase inhibitor and bLF on the concentration of levodopa in blood and its metabolism were assessed in eight healthy subjects. In addition, we analyzed the association with clinical factors and evaluated whether clinical factors affected the COMT inhibitory activity of bLF in vitro.Results: Although not statistically significant, the peak plasma concentration (Cmax) of levodopa increased by 18.5%. From the results of the stratified analysis of total cholesterol, a relationship with ΔCmax was predicted. Therefore, bLF was reacted with cholesterol in the presence of lecithin and sodium deoxycholate in vitro to evaluate COMT inhibitory activity, and an increase in inhibitory activity was observed. By contrast, the ester compound cholesteryl oleate had no effect. The inhibitory activity of free fatty acids, which are known to interact with bLF, was also enhanced.Conclusion: The COMT inhibitory activity of bLF is not effective in elevating blood levodopa levels. However, in humans with high lipid levels, such as cholesterol, interactions may enhance the inhibitory effect, resulting in the enhanced absorption of levodopa.Trial registration: ID, UMIN000026787, registered 30 March 2017; URL, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030749Trial registration: UMIN Japan identifier: UMIN000026787.
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Affiliation(s)
- Masahiro Nagai
- Department of Neurology and Clinical Pharmacology, Ehime University Hospital
| | - Madoka Kubo
- Department of Neurology and Clinical Pharmacology, Ehime University Hospital
| | - Rina Ando
- Department of Neurology and Clinical Pharmacology, Ehime University Hospital
| | - Masayuki Ikeda
- Wellness & Nutrition Science Institute, R&D Division, Morinaga Milk Industry Co., Ltd
| | - Hiroshi Iwamoto
- Wellness & Nutrition Science Institute, R&D Division, Morinaga Milk Industry Co., Ltd
| | - Yasuhiro Takeda
- Wellness & Nutrition Science Institute, R&D Division, Morinaga Milk Industry Co., Ltd
| | - Masahiro Nomoto
- Department of Neurology and Clinical Pharmacology, Ehime University Hospital
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25
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Singh A, Zapata RC, Pezeshki A, Knight CG, Tuor UI, Chelikani PK. Whey Protein and Its Components Lactalbumin and Lactoferrin Affect Energy Balance and Protect against Stroke Onset and Renal Damage in Salt-Loaded, High-Fat Fed Male Spontaneously Hypertensive Stroke-Prone Rats. J Nutr 2020; 150:763-774. [PMID: 31879775 DOI: 10.1093/jn/nxz312] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Revised: 10/20/2019] [Accepted: 11/26/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Whey protein (WH)-enriched diets are reported to aid in weight loss and to improve cardiovascular health. However, the bioactive components in whey responsible for causing such effects remain unidentified. OBJECTIVE We determined the effects of whey and its components [α-lactalbumin (LA) and lactoferrin (LF)] on energy balance, glucose tolerance, gut hormones, renal damage, and stroke onset in rats. METHODS Male spontaneously hypertensive stroke-prone (SHRSP) rats (age 8 wk) were fed isocaloric high-fat (40% kcal) and high-salt (4% wt/wt) diets (n = 8-10/group) and randomized for 8 wk to diets enriched as follows: control (CO): 15% kcal from egg albumin, 45% kcal from carbohydrate; WH: 20%kcal WH isolate + 15% kcal egg albumin; LA: 20% kcal LA + 15% kcal egg albumin; or LF: 20% kcal lactoferrin + 15% kcal egg albumin. Measurements included energy balance (food intake, energy expenditure, and body composition), stroke-related behaviors, brain imaging, glucose tolerance, metabolic hormones, and tissue markers of renal damage. Data were analyzed by linear mixed models with repeated measures or 1-way ANOVA. RESULTS Diets enriched with WH, LA, or LF increased survival, with 25% of rats fed these diets exhibiting stroke-associated morbidity, whereas 90% of CO rats were morbid by 8 wk (P < 0.05). The nephritis scores of rats fed WH-, LA-, or LF-enriched diets were 80%, 92%, and 122% lower than those of COs (P = 0.001). The mRNA abundances of renin and osteopontin were 100-600% lower in rats fed WH-, LA-, or LF-enriched diets than in COs (P < 0.05). Urine albumin concentrations and albumin-to-creatinine ratios were 200% lower in rats fed LF-enriched diets than in COs (P < 0.05). Compared with COs, rats fed LF-enriched diets for 2-3 wk had food intake decreased by 29%, body weight decreased by 13-19%, lean mass decreased by 12-19%, and fat mass decreased by 20% (P < 0.001). Relative to COs, rats fed WH and LA had food intake decreased by 10% (P < 0.1), but COs had 12-45% lower weight than rats fed LA- and WH-enriched diets by 3 wk (P < 0.01). Compared with COs, rats fed WH-enriched diets increased energy expenditure by 7%, whereas, rats fed LA-enriched diets had energy expenditure acutely decreased by 7% during the first 4 d, and rats fed LF-enriched diets had energy expenditure decreased by 7-17% throughout the first week ( P < 0.001). Rats fed LA- and LF-enriched diets had blood glucose decreased by 14-19% (P < 0.05) and WH by 9% (P = 0.1), relative to COs. Compared with COs, rats fed LF had GIP decreased by 90% and PYY by 87% (P < 0.05). CONCLUSION Together, these findings indicate that whey and its components α-lactalbumin and lactoferrin improved energy balance and glycemic control, and protected against the onset of neurological deficits associated with stroke and renal damage in male SHRSP rats.
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Affiliation(s)
- Arashdeep Singh
- Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Alberta, Canada
| | - Rizaldy C Zapata
- Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Alberta, Canada
| | - Adel Pezeshki
- Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Alberta, Canada
| | - Cameron G Knight
- Department of Veterinary Clinical and Diagnostic Sciences, Faculty of Veterinary Medicine, University of Calgary, Alberta, Canada
| | - Ursula I Tuor
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Alberta, Canada
| | - Prasanth K Chelikani
- Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Alberta, Canada
- Gastrointestinal Research Group, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta Canada
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26
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Gewehr MCF, Silverio R, Rosa-Neto JC, Lira FS, Reckziegel P, Ferro ES. Peptides from Natural or Rationally Designed Sources Can Be Used in Overweight, Obesity, and Type 2 Diabetes Therapies. Molecules 2020; 25:E1093. [PMID: 32121443 PMCID: PMC7179135 DOI: 10.3390/molecules25051093] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 02/20/2020] [Accepted: 02/25/2020] [Indexed: 12/18/2022] Open
Abstract
Overweight and obesity are among the most prominent health problems in the modern world, mostly because they are either associated with or increase the risk of other diseases such as type 2 diabetes, hypertension, and/or cancer. Most professional organizations define overweight and obesity according to individual body-mass index (BMI, weight in kilograms divided by height squared in meters). Overweight is defined as individuals with BMI from 25 to 29, and obesity as individuals with BMI ≥30. Obesity is the result of genetic, behavioral, environmental, physiological, social, and cultural factors that result in energy imbalance and promote excessive fat deposition. Despite all the knowledge concerning the pathophysiology of obesity, which is considered a disease, none of the existing treatments alone or in combination can normalize blood glucose concentration and prevent debilitating complications from obesity. This review discusses some new perspectives for overweight and obesity treatments, including the use of the new orally active cannabinoid peptide Pep19, the advantage of which is the absence of undesired central nervous system effects usually experienced with other cannabinoids.
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Affiliation(s)
- Mayara C. F. Gewehr
- Department of Pharmacology, Biomedical Sciences Institute, University of São Paulo (USP), São Paulo 05508-000, Brazil;
| | - Renata Silverio
- Department of Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina (UFSC), Florianópolis 88040-900, Brazil;
| | - José Cesar Rosa-Neto
- Department of Cell and Developmental Biology, Biomedical Sciences Institute, University of São Paulo (USP), São Paulo 05508-000, Brazil;
| | - Fabio S. Lira
- Department of Physical Education, São Paulo State University (UNESP), Presidente Prudente 19060-900, Brazil;
| | - Patrícia Reckziegel
- Department of Pharmacology, National Institute of Pharmacology and Molecular Biology (INFAR), Federal University of São Paulo (UNIFESP), São Paulo 05508-000, Brazil;
| | - Emer S. Ferro
- Department of Pharmacology, Biomedical Sciences Institute, University of São Paulo (USP), São Paulo 05508-000, Brazil;
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Matsuoka R, Takahashi Y, Muto A, Kimura M. Heated egg white has no effect, but lactic fermented and unheated egg white reduces abdominal fat in rats. Lipids Health Dis 2019; 18:187. [PMID: 31655590 PMCID: PMC6815000 DOI: 10.1186/s12944-019-1133-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2019] [Accepted: 10/16/2019] [Indexed: 11/18/2022] Open
Abstract
Background We previously reported the abdominal fat-reducing effect of unheated egg white proteins (EWP); however, unheated egg white is actually rarely consumed. We thus investigated the effect of heated egg white on abdominal fat in rats. Methods Male SD rats were divided into two groups that were allowed to consume different dietary preparations containing casein or heated egg white for 4 weeks (Trial 1). We studied whether a heated form and a lactic fermented form of egg white (FLE) are as effective as unheated egg white for reducing abdominal fat. For this, we divided male SD rats into four groups that were allowed to consume different dietary preparations containing casein, unheated egg white, heated egg white, or lactic fermented egg white for 4 weeks (Trial 2). Results Animals in the heated egg white group showed no significant difference in abdominal fat weight compared with those in the casein group (Trial 1). Animals in the unheated egg white group and the FLE group had significantly lower levels of abdominal fat weight than those in the casein group (Trial 2). Ovalbumin in heated egg white was degraded by pepsin, whereas ovalbumin in unheated egg white and lactic acid fermented egg white was not degraded appreciably by pepsin. It was reported that EWP inhibit triglyceride absorption in rat. In the present study, EWP pepsin hydrolysate inhibited the micellar solubility of fatty acids in vitro. In particular, ovalbumin inhibited the micellar solubility of fatty acids. Conclusions These results indicate that lactic fermented egg white reduces visceral fat in rats and suggest that different levels of susceptibility of ovalbumin to pepsin digestion underlie the varying effectiveness among the egg white preparations.
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Affiliation(s)
- Ryosuke Matsuoka
- R & D Division, Kewpie Corporation, Sengawa Kewport, 2-5-7, Sengawa-cho, Chofu-shi, Tokyo, 182-0002, Japan.
| | - Yayoi Takahashi
- R & D Division, Kewpie Corporation, Sengawa Kewport, 2-5-7, Sengawa-cho, Chofu-shi, Tokyo, 182-0002, Japan
| | - Ayano Muto
- R & D Division, Kewpie Corporation, Sengawa Kewport, 2-5-7, Sengawa-cho, Chofu-shi, Tokyo, 182-0002, Japan
| | - Mamoru Kimura
- R & D Division, Kewpie Corporation, Sengawa Kewport, 2-5-7, Sengawa-cho, Chofu-shi, Tokyo, 182-0002, Japan
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Matsuoka R, Kamachi K, Usuda M, Masuda Y, Kunou M, Tanaka A, Utsunomiya K. Minimal effective dose of lactic-fermented egg white on visceral fat in Japanese men: a double-blind parallel-armed pilot study. Lipids Health Dis 2019; 18:102. [PMID: 31010430 PMCID: PMC6477745 DOI: 10.1186/s12944-019-1047-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 04/08/2019] [Indexed: 11/23/2022] Open
Abstract
Background We previously reported that the consumption of 8 g of protein per day in the form of lactic-fermented egg white (LAFEW) improves visceral fat obesity. In this study, we investigated the minimum effective intake of LAFEW for visceral fat reduction in the Japanese males with mild obesity. Methods Twenty-two Japanese adult males with a Body mass index (BMI) ≥24 and a waist circumference ≥ 85 cm were included in this study. The subjects were divided into three groups, that is, control group, LAFEW 6 g group, and LAFEW 8 g group. The LAFEW 6 and 8 g groups consumed 6 and 8 g, respectively, of egg white protein (EWP) in a drink at breakfast for 8 weeks, whereas the control group consumed a drink containing 8 g of milk whey protein. Body weight, body fat percentage, abdominal circumference, and visceral fat (VF) area around the navel were measured at 0 and 8 weeks after initiating the consumption. Results No changes in body weight or body fat percentage were observed in any of the groups. No significant differences between the pre- and posttreatment measurements were found in the VF area around the navel in the control group and the LAFEW 6 g group. In the LAFEW 8 g group, the VF area had decreased significantly after 8 weeks of consumption, when compared to that before consumption, and the average observed decrease (Δcm2) was 13.2 ± 4.7 cm2. Among the subjects with an initial BMI > 25, the VF area was significantly smaller in the LAFEW 8 group, when compared to the week 0 values and those in the control group. Visceral fat/subcutaneous fat values in the LAFEW 8 group were also significantly smaller than those in the control group or at week 0. Conclusion The results suggested that the minimum effective intake of EWP in the LAFEW to reduce the VF area in the Japanese men is 8 g. Trial registration This clinical trial was retrospectively registered with the University hospital Medical Information Network (UMIN) Center, (UMIN000031681; registered on 12/03/2018).
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Affiliation(s)
- Ryosuke Matsuoka
- R&D Division, Kewpie Corporation, 2-5-7 Sengawa Kewport, Sengawa-Cho, Chofu-Shi, Tokyo, 182-0002, Japan.
| | - Keiko Kamachi
- Nutrition Clinic, Kagawa Nutrition University, Komagome, Toshima-ku, Tokyo, 170-8481, Japan
| | - Mika Usuda
- R&D Division, Kewpie Corporation, 2-5-7 Sengawa Kewport, Sengawa-Cho, Chofu-Shi, Tokyo, 182-0002, Japan
| | - Yasunobu Masuda
- R&D Division, Kewpie Corporation, 2-5-7 Sengawa Kewport, Sengawa-Cho, Chofu-Shi, Tokyo, 182-0002, Japan
| | - Masaaki Kunou
- R&D Division, Kewpie Corporation, 2-5-7 Sengawa Kewport, Sengawa-Cho, Chofu-Shi, Tokyo, 182-0002, Japan
| | - Akira Tanaka
- Nutrition Clinic, Kagawa Nutrition University, Komagome, Toshima-ku, Tokyo, 170-8481, Japan
| | - Kazunori Utsunomiya
- Division of Diabetes, Metabolism & Endocrinology, Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
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Effects of Metformin Combined with Lactoferrin on Lipid Accumulation and Metabolism in Mice Fed with High-Fat Diet. Nutrients 2018; 10:nu10111628. [PMID: 30400147 PMCID: PMC6265902 DOI: 10.3390/nu10111628] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Revised: 10/15/2018] [Accepted: 10/22/2018] [Indexed: 12/17/2022] Open
Abstract
Metformin (Met) and lactoferrin (Lf) both exhibit beneficial effects on body weight management and lipid accumulation. However, the synergistical action of Met and Lf remains unclear. In this study, 64 mice were divided into five groups, namely, the control group, high-fat diet (HFD group), HFD with Met (Met group), Lf (Lf group), and a combination of Met and Lf (Met + Lf group). Met (200 mg/kg body weight) and Lf (2 g/100 mL) were administrated in drinking water. The experiment lasted for 12 weeks. Body weight, serum, and hepatic lipids were determined. Histology of the liver and perirenal fat was observed. Protein expression related to hepatic lipid metabolism was also measured. HFD significantly increased body weight, visceral fat weight, and lipid profiles, which lead to obesity and dyslipidemia in mice. Compared with the HFD group, the treatments significantly decreased body weight and Lee’s index (body mass index of mice) with the lowest values in the Met + Lf group. The treatments also decreased the weight of visceral fat, and improved circulating lipid profile and the ability for regulating glucose intake. The adipocyte size and serum TC level were significantly lower in the Met + Lf group as compared with those in the Met or Lf group. The treatments alleviated hepatic lipid accumulation, especially in the Met + Lf group. For protein expression, the p-AMPK/AMPK ratio, a key kinase-regulating cellular energy homeostasis, was significantly higher in the Met + Lf group than the ratio in the HFD group. Similarly, the treatments significantly downregulated the protein expression of lipogenic enzymes (FAS, ACC, and SREBP-1) and upregulated the protein expression of lipolytic enzyme (ATGL). The protein expression of HMGCoAR, which is an important rate limiting enzyme in cholesterol biosynthesis, was only significantly lower in the Met + Lf group than in the HFD group. In conclusion, Met and Lf, either alone or in combination, prevented HFD-induced obesity and improved lipid metabolism.
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Erythropoietin and Nrf2: key factors in the neuroprotection provided by apo-lactoferrin. Biometals 2018; 31:425-443. [PMID: 29748743 DOI: 10.1007/s10534-018-0111-9] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Accepted: 05/03/2018] [Indexed: 02/06/2023]
Abstract
Among the properties of lactoferrin (LF) are bactericidal, antianemic, immunomodulatory, antitumour, antiphlogistic effects. Previously we demonstrated its capacity to stabilize in vivo HIF-1-alpha and HIF-2-alpha, which are redox-sensitive multiaimed transcription factors. Various tissues of animals receiving recombinant human LF (rhLF) responded by expressing the HIF-1-alpha target genes, hence such proteins as erythropoietin (EPO), ceruloplasmin, etc. were synthesized in noticeable amounts. Among organs in which EPO synthesis occurred were brain, heart, spleen, liver, kidneys and lungs. Other researchers showed that EPO can act as a protectant against severe brain injury and status epilepticus in rats. Therefore, we tried rhLF as a protector against the severe neurologic disorders developed in rats, such as the rotenone-induced model of Parkinson's disease and experimental autoimmune encephalomyelitis as a model of multiple sclerosis, and observed its capacity to mitigate the grave symptoms. Moreover, an intraperitoneal injection of rhLF into mice 1 h after occlusion of the medial cerebral artery significantly diminished the necrosis area measured on the third day in the ischaemic brain. During this period EPO was synthesized in various murine tissues. It was known that EPO induces nuclear translocation of Nrf2, which, like HIF-1-alpha, is a transcription factor. In view that under conditions of hypoxia both factors demonstrate a synergistic protective effect, we suggested that LF activates the Keap1/Nrf2 signaling pathway, an important link in proliferation and differentiation of normal and malignant cells. J774 macrophages were cultured for 3 days without or in the presence of ferric and ferrous ions (RPMI-1640 and DMEM/F12, respectively). Then cells were incubated with rhLF or Deferiprone. Confocal microscopy revealed nuclear translocation of Nrf2 (the key event in Keap1/Nrf2 signaling) induced by apo-rhLF (iron-free, RPMI-1640). The reference compound Deferiprone (iron chelator) had the similar effect. Upon iron binding (in DMEM/F12) rhLF did not activate the Keap1/Nrf2 pathway. Added to J774, apo-rhLF enhanced transcription of Nrf2-dependent genes coding for glutathione S-transferase P and heme oxygenase-1. Western blotting revealed presence of Nrf2 in mice brain after 6 days of oral administration of apo-rhLF, but not Fe-rhLF or equivalent amount of PBS. Hence, apo-LF, but not holo-LF, induces the translocation of Nrf2 from cytoplasm to the nucleus, probably due to its capacity to induce EPO synthesis.
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31
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Nakamura K, Kishida T, Ejima A, Tateyama R, Morishita S, Ono T, Murakoshi M, Sugiyama K, Nishino H, Mazda O. Bovine lactoferrin promotes energy expenditure via the cAMP-PKA signaling pathway in human reprogrammed brown adipocytes. Biometals 2018; 31:415-424. [PMID: 29744695 DOI: 10.1007/s10534-018-0103-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Accepted: 04/05/2018] [Indexed: 11/26/2022]
Abstract
Lactoferrin (LF) is a multifunctional protein in mammalian milk. We previously reported that enteric-coated bovine LF reduced the visceral fat in a double-blind clinical study. We further demonstrated that bovine LF (bLF) inhibited adipogenesis and promoted lipolysis in white adipocytes, but the effect of bLF on brown adipocytes has not been clarified. In this study, we investigated the effects of bLF on energy expenditure and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway using human reprogrammed brown adipocytes generated by gene transduction. bLF at concentrations of ≥ 100 μg/mL significantly increased uncoupling protein 1 (UCP1) mRNA levels, with the maximum value observed 4 h after bLF addition. At the same time point, bLF stimulation also significantly increased oxygen consumption. Signaling pathway analysis revealed rapid increases of intracellular cAMP and cAMP response element-binding protein (CREB) phosphorylation levels beginning 5 min after bLF addition. The mRNA levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) were also significantly increased after 1 h of bLF stimulation. H-89, a specific PKA inhibitor, abrogated bLF-induced UCP1 gene expression. Moreover, receptor-associated protein (Rap), an antagonist of low-density lipoprotein receptor-related protein 1 (LRP1), significantly reduced bLF-induced UCP1 gene expression in a dose-dependent manner. These results suggest that bLF promotes UCP1 gene expression in brown adipocytes through the cAMP-PKA signaling pathway via the LRP1 receptor, leading to increased energy expenditure.
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Affiliation(s)
- Kanae Nakamura
- Research and Development Headquarters, Lion Corporation, 100 Tajima, Odawara, Kanagawa, 256-0811, Japan
| | - Tsunao Kishida
- Department of Immunology, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto, 602-8566, Japan
| | - Akika Ejima
- Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto, 606-8502, Japan
| | - Riho Tateyama
- Research and Development Headquarters, Lion Corporation, 100 Tajima, Odawara, Kanagawa, 256-0811, Japan
| | - Satoru Morishita
- Research and Development Headquarters, Lion Corporation, 100 Tajima, Odawara, Kanagawa, 256-0811, Japan
- "Food for Life", Organization for Interdisciplinary Research Projects, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan
| | - Tomoji Ono
- Research and Development Headquarters, Lion Corporation, 100 Tajima, Odawara, Kanagawa, 256-0811, Japan
- Advanced Medical Research Center, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
| | - Michiaki Murakoshi
- Research and Development Headquarters, Lion Corporation, 100 Tajima, Odawara, Kanagawa, 256-0811, Japan
- Advanced Medical Research Center, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
- Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, 602-0841, Japan
| | - Keikichi Sugiyama
- Research Organization of Science and Engineering, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan
| | - Hoyoku Nishino
- Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, 602-0841, Japan
| | - Osam Mazda
- Department of Immunology, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto, 602-8566, Japan.
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Evaluation of randomized controlled trials of foods with functional claims request: The learning outcomes from studies in Japan. J Funct Foods 2018. [DOI: 10.1016/j.jff.2017.12.066] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Zapata RC, Singh A, Chelikani PK. Peptide YY mediates the satiety effects of diets enriched with whey protein fractions in male rats. FASEB J 2018; 32:850-861. [PMID: 29042449 DOI: 10.1096/fj.201700519rr] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Dairy proteins-whey protein, in particular-are satiating and often recommended for weight control; however, little is known about the mechanisms by which whey protein and its components promote satiety and weight loss. We used diet-induced obese rats to determine whether the hypophagic effects of diets that are enriched with whey and its fractions, lactalbumin and lactoferrin, are mediated by the gut hormone, peptide YY (PYY). We demonstrate that high protein diets that contain whey, lactalbumin, and lactoferrin decreased food intake and body weight with a concurrent increase in PYY mRNA abundance in the colon and/or plasma PYY concentrations. Of importance, blockade of PYY neuropeptide Y receptor subtype 2 (Y2) receptors with a peripherally restricted antagonist attenuated the hypophagic effects of diets that are enriched with whey protein fractions. Diets that are enriched with whey fractions were less preferred; however, in a modified conditioned taste preference test, PYY Y2 receptor blockade induced hyperphagia of a lactoferrin diet, but caused a reduction in preference for Y2 antagonist-paired flavor, which suggested that PYY signaling is important for lactoferrin-induced satiety, but not essential for preference for lactoferrin-enriched diets. Taken together, these data provide evidence that the satiety of diets that are enriched with whey protein components is mediated, in part, via enhanced PYY secretion and action in obese male rats.-Zapata, R. C., Singh, A., Chelikani, P. K. Peptide YY mediates the satiety effects of diets enriched with whey protein fractions in male rats.
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Affiliation(s)
- Rizaldy C Zapata
- Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Arashdeep Singh
- Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Prasanth K Chelikani
- Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.,Gastrointestinal Research Group, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
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Xiong L, Ren F, Lv J, Zhang H, Guo H. Lactoferrin attenuates high-fat diet-induced hepatic steatosis and lipid metabolic dysfunctions by suppressing hepatic lipogenesis and down-regulating inflammation in C57BL/6J mice. Food Funct 2018; 9:4328-4339. [DOI: 10.1039/c8fo00317c] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Lactoferrin was reported to exert modulatory effects on lipid metabolism, but the regulatory mechanisms remain unclear.
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Affiliation(s)
- Ling Xiong
- Beijing Advanced Innovation Center for Food Nutrition and Human Health
- College of Food Science & Nutritional Engineering
- China Agricultural University
- Beijing 100083
- China
| | - Fazheng Ren
- Beijing Advanced Innovation Center for Food Nutrition and Human Health
- College of Food Science & Nutritional Engineering
- China Agricultural University
- Beijing 100083
- China
| | - Jiayi Lv
- Key Laboratory of Functional Dairy
- Co-constructed by the Ministry of Education and Beijing Government
- China Agricultural University
- Beijing 100083
- China
| | - Hao Zhang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health
- College of Food Science & Nutritional Engineering
- China Agricultural University
- Beijing 100083
- China
| | - Huiyuan Guo
- Beijing Advanced Innovation Center for Food Nutrition and Human Health
- College of Food Science & Nutritional Engineering
- China Agricultural University
- Beijing 100083
- China
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Matsuoka R, Kamachi K, Usuda M, Wang W, Masuda Y, Kunou M, Tanaka A, Utsunomiya K. Lactic-fermented egg white improves visceral fat obesity in Japanese subjects-double-blind, placebo-controlled study. Lipids Health Dis 2017; 16:237. [PMID: 29216922 PMCID: PMC5721610 DOI: 10.1186/s12944-017-0631-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Accepted: 11/29/2017] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND It was reported that egg white protein (EWP) reduced body fat in rats. We developed a lactic-fermented egg white (LE) that facilitates the consumption of egg whites by fermenting them with lactobacillus, and were able to study their intake in humans. In this double-blind, placebo-controlled design, we evaluated the effect of LE on visceral fat area (VFA). METHODS Participants included 37 adult males and females aged ≥40 years (VFA at navel ≥100 cm2). They were divided into two groups: the control group and the LE group. The control and LE groups consumed drinks containing whey and LE, respectively, for 12 weeks (providing 8 g protein/day). VFA was measured at baseline and at week 12 of intake. Abdominal girth was measured at baseline and at weeks 6 and 12. RESULTS LE intake decreased VFA significantly compared with baseline (-8.89 cm2, p < 0.05), and VFA was significantly lower than that in the control group (+1.71 cm2, p < 0.05). The LE group showed significant improvement in the ratio of visceral to subcutaneous fat area compared with baseline and the control group (p < 0.05). CONCLUSIONS The results demonstrated that LE reduces VFA and improves the ratio of visceral to subcutaneous fat area. As other measurement items were not influenced, we concluded that LE improves visceral fat obesity. TRIAL REGISTRATION This clinical trial was retrospectively registered with the University hospital Medical Information Network (UMIN) Center, ( UMIN000026949 ; registered on 11/04/2017; http://www.umin.ac.jp /).
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Affiliation(s)
- Ryosuke Matsuoka
- R&D Division, Kewpie Corporation, 2-5-7 Sengawa Kewport, Sengawa-Cho, Chofu-Shi, Tokyo, 182-0002 Japan
| | - Keiko Kamachi
- Nutrition Clinic, Kagawa Nutrition University, 3-24-3, Komagome, Toshima-ku, Tokyo, 170-8481 Japan
| | - Mika Usuda
- R&D Division, Kewpie Corporation, 2-5-7 Sengawa Kewport, Sengawa-Cho, Chofu-Shi, Tokyo, 182-0002 Japan
| | - Wei Wang
- R&D Division, Kewpie Corporation, 2-5-7 Sengawa Kewport, Sengawa-Cho, Chofu-Shi, Tokyo, 182-0002 Japan
| | - Yasunobu Masuda
- R&D Division, Kewpie Corporation, 2-5-7 Sengawa Kewport, Sengawa-Cho, Chofu-Shi, Tokyo, 182-0002 Japan
| | - Masaaki Kunou
- R&D Division, Kewpie Corporation, 2-5-7 Sengawa Kewport, Sengawa-Cho, Chofu-Shi, Tokyo, 182-0002 Japan
| | - Akira Tanaka
- Nutrition Clinic, Kagawa Nutrition University, 3-24-3, Komagome, Toshima-ku, Tokyo, 170-8481 Japan
| | - Kazunori Utsunomiya
- Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo, 105-8461 Japan
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Cardiometabolic risk factors and lactoferrin: polymorphisms and plasma levels in French-Canadian children. Pediatr Res 2017; 82:741-748. [PMID: 28678770 DOI: 10.1038/pr.2017.72] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Accepted: 02/11/2017] [Indexed: 01/13/2023]
Abstract
BackgroundLactoferrin (LTF) could play a beneficial role in insulin resistance and diabetes, but the association of its gene variants with cardio-metabolic disorders in children has not been investigated. This study aimed to examine the relationship between LTF variants, plasma LTF concentrations, and cardio-metabolic risk factors in French-Canadian children.MethodsThe study cohort comprises 1,749 French Canadians aged 9, 13, and 16 years. The association of 13 LTF polymorphisms, metabolic parameters, and plasma LTF levels was tested in this cross-sectional, province-wide school-based survey.ResultsNone of the genetic association remained significant after correction for multiple testing and LTF SNPs were not associated with LTF levels. Plasma LTF was positively correlated with body mass index (r2=0.2245, P=0.0011) and weight (r2=0.2515, P=0.0008). After segregating according to high-density lipoprotein cholesterol (HDL-C), the association remained only in subjects exhibiting low HDL-C (r2=0.3868, P=0.0002 for body mass index and r2=0.3665, P=0.0004 for weight). In girls, plasma LTF was positively correlated with total cholesterol (r2=0.2231, P=0.0378), LDL cholesterol (r2=0.2409, P=0.0246), and apolipoprotein B (r2=0.2478, P=0.0207).ConclusionsWe found no association between LTF gene variants and metabolic parameters following correction for multiple testing. HDL-C and gender-specific positive associations were evidenced between plasma LTF, anthropometric profile, and lipid levels.
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Dietary egg-white protein increases body protein mass and reduces body fat mass through an acceleration of hepaticβ-oxidation in rats. Br J Nutr 2017; 118:423-430. [DOI: 10.1017/s0007114517002306] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
AbstractEgg-white protein (EWP) is known to reduce lymphatic TAG transport in rats. In this study, we investigated the effects of dietary EWP on body fat mass. Male rats, 4 weeks old, were fed diets containing either 20 % EWP or casein for 28 d. Carcass protein levels and gastrocnemius leg muscle weights in the EWP group were significantly higher than those in the casein group. In addition, carcass TAG levels and abdominal fat weights in the EWP group were significantly lower than those in the casein group; adipocyte size in abdominal fat in the EWP group was smaller than that in the casein group. To identify the involvement of dietary fat levels in the rats, one of two fat levels (5 or 10 %) was added to their diet along with the different protein sources (EWP and casein). Abdominal fat weight and serum and hepatic TAG levels were significantly lower in the EWP group than in the casein group. Moreover, significantly higher values of enzymatic activity related toβ-oxidation in the liver were observed in the EWP group compared with the casein group. Finally, abdominal fat weight reduction in the EWP group with the 10 % fat diet was lower than that in the EWP group with the 5 % fat diet. In conclusion, our results indicate that, in addition to the inhibition of dietary TAG absorption reported previously, dietary EWP reduces body fat mass in rats through an increase of body protein mass and the acceleration ofβ-oxidation in the liver.
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Aizawa S, Hoki M, Yamamuro Y. Lactoferrin promotes autophagy via AMP-activated protein kinase activation through low-density lipoprotein receptor-related protein 1. Biochem Biophys Res Commun 2017; 493:509-513. [PMID: 28867180 DOI: 10.1016/j.bbrc.2017.08.160] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Accepted: 08/31/2017] [Indexed: 12/19/2022]
Abstract
Lactoferrin (LF) is a multifunctional, iron-binding glycoprotein in mammalian secretions, such as breast milk, and has several beneficial effects for human health. However, how these effects are exerted at the cellular level is still largely unknown. In this study, we investigated the effects of LF on autophagy activity in NIH/3T3 mouse fibroblasts. LF from bovine milk was found to increase LC3-I to LC3-II conversion and LC3-positive cytosolic punctate structures because of increased autophagy flux. Knockdown of the putative LF receptor low-density receptor-related protein 1 (LRP1) completely abolished LC3 conversion in cells by LF treatment. Moreover, exposure to LF increased the phosphorylation levels of AMPK in cells, and treatment of dorsomorphin, a pharmacological inhibitor of AMPK signaling, attenuated LC3 conversion by LF. Therefore, we concluded that the beneficial effects of LF might be due to an increase of autophagy activity via AMPK signaling through the LRP1 receptor. These findings provide a novel insight into the physiological role of LF for the maintenance of cellular and tissue homeostasis.
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Affiliation(s)
- Shu Aizawa
- Laboratory of Animal Genetics and Physiology, Department of Animal Science, College of Bioresource Sciences, Nihon University, Japan.
| | - Minami Hoki
- Laboratory of Animal Genetics and Physiology, Department of Animal Science, College of Bioresource Sciences, Nihon University, Japan
| | - Yutaka Yamamuro
- Laboratory of Animal Genetics and Physiology, Department of Animal Science, College of Bioresource Sciences, Nihon University, Japan.
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Zapata RC, Singh A, Pezeshki A, Nibber T, Chelikani PK. Whey Protein Components - Lactalbumin and Lactoferrin - Improve Energy Balance and Metabolism. Sci Rep 2017; 7:9917. [PMID: 28855697 PMCID: PMC5577213 DOI: 10.1038/s41598-017-09781-2] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Accepted: 07/28/2017] [Indexed: 02/07/2023] Open
Abstract
Whey protein promotes weight loss and improves diabetic control, however, less is known of its bioactive components that produce such benefits. We compared the effects of normal protein (control) diet with high protein diets containing whey, or its fractions lactalbumin and lactoferrin, on energy balance and metabolism. Diet-induced obese rats were randomized to isocaloric diets: Control, Whey, Lactalbumin, Lactoferrin, or pair-fed to lactoferrin. Whey and lactalbumin produced transient hypophagia, whereas lactoferrin caused prolonged hypophagia; the hypophagia was likely due to decreased preference. Lactalbumin decreased weight and fat gain. Notably, lactoferrin produced sustained weight and fat loss, and attenuated the reduction in energy expenditure associated with calorie restriction. Lactalbumin and lactoferrin decreased plasma leptin and insulin, and lactalbumin increased peptide YY. Whey, lactalbumin and lactoferrin improved glucose clearance partly through differential upregulation of glucoregulatory transcripts in the liver and skeletal muscle. Interestingly, lactalbumin and lactoferrin decreased hepatic lipidosis partly through downregulation of lipogenic and/or upregulation of β-oxidation transcripts, and differentially modulated cecal bacterial populations. Our findings demonstrate that protein quantity and quality are important for improving energy balance. Dietary lactalbumin and lactoferrin improved energy balance and metabolism, and decreased adiposity, with the effects of lactoferrin being partly independent of caloric intake.
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Affiliation(s)
- Rizaldy C Zapata
- Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada
| | - Arashdeep Singh
- Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada
| | - Adel Pezeshki
- Department of Animal Science, Oklahoma State University, Stillwater, Oklahoma, 74078, USA
| | - Traj Nibber
- Advanced Orthomolecular Research, 3900 12 St NE, Calgary, Alberta, T2E 6X8, Canada
| | - Prasanth K Chelikani
- Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada. .,Gastrointestinal Research Group, Snyder Institute for Chronic Diseases, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada.
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40
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Singh A, Zapata RC, Pezeshki A, Chelikani PK. Dietary lactalbumin and lactoferrin interact with inulin to modulate energy balance in obese rats. Obesity (Silver Spring) 2017; 25:1050-1060. [PMID: 28437574 DOI: 10.1002/oby.21840] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Accepted: 03/13/2017] [Indexed: 11/07/2022]
Abstract
OBJECTIVE To determine whether diets enriched with the whey protein components lactalbumin and lactoferrin interact additively with inulin to improve energy balance by decreasing food intake and body weight (BW). METHODS In four experiments, diet-induced obese rats were randomized to diets containing either lactalbumin or lactoferrin at low (20% kcal) or high (40% kcal) doses, and inulin at low (7.5% w/w) or high (15% w/w) doses, alone or in combination. Energy intake (EI), energy expenditure (EE), respiratory quotient (RQ), BW, body composition, plasma insulin, and leptin concentrations were measured. RESULTS Lactalbumin and inulin at low doses were ineffective, whereas high doses additively decreased EI and RQ. Low doses of lactoferrin and inulin additively decreased EI, BW, fat and lean mass, and RQ. High doses of lactoferrin and inulin additively decreased EI, supra-additively decreased BW, fat, and lean mass, and also decreased RQ and plasma leptin concentrations. CONCLUSIONS High doses of lactalbumin and inulin additively decreased EI. Importantly, lactoferrin and inulin at both low and high dose combinations, additively or supra-additively, decreased EI, BW, and adiposity.
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Affiliation(s)
- Arashdeep Singh
- Department of Production Animal Health, Faculty of Veterinary Medicine, Gastrointestinal Research Group, Snyder Institute for Chronic Diseases, University of Calgary, Alberta, Canada
| | - Rizaldy C Zapata
- Department of Production Animal Health, Faculty of Veterinary Medicine, Gastrointestinal Research Group, Snyder Institute for Chronic Diseases, University of Calgary, Alberta, Canada
| | - Adel Pezeshki
- Department of Animal Science, Oklahoma State University, Stillwater, Oklahoma, USA
| | - Prasanth K Chelikani
- Department of Production Animal Health, Faculty of Veterinary Medicine, Gastrointestinal Research Group, Snyder Institute for Chronic Diseases, University of Calgary, Alberta, Canada
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Brimelow RE, West NP, Williams LT, Cripps AW, Cox AJ. A role for whey-derived lactoferrin and immunoglobulins in the attenuation of obesity-related inflammation and disease. Crit Rev Food Sci Nutr 2017; 57:1593-1602. [PMID: 26068582 DOI: 10.1080/10408398.2014.995264] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Obesity is a strong predictive factor in the development of chronic disease and has now superseded undernutrition as a major public health issue. Chronic inflammation is one mechanism thought to link excess body weight with disease. Increasingly, the gut and its extensive population of commensal microflora are recognized as playing an important role in the development of obesity-related chronic inflammation. Obesity and a high fat diet are associated with altered commensal microbial communities and increased intestinal permeability which contributes to systemic inflammation as a result of the translocation of lipopolysaccharide into the circulation and metabolic endotoxemia. Various milk proteins are showing promise in the prevention and treatment of obesity and chronic low-grade inflammation via reductions in visceral fat, neutralization of bacteria at the mucosa and reduced intestinal permeability. In this review, we focus on evidence supporting the potential antiobesogenic and anti-inflammatory effects of bovine whey-derived lactoferrin and immunoglobulins.
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Affiliation(s)
- Rachel E Brimelow
- a School of Medical Science, Griffith University , Southport , Queensland , Australia
| | - Nicholas P West
- a School of Medical Science, Griffith University , Southport , Queensland , Australia.,b Menzies Health Institute Queensland , Southport , Queensland , Australia
| | - Lauren T Williams
- b Menzies Health Institute Queensland , Southport , Queensland , Australia.,c School of Allied Health Sciences, Griffith University , Southport , Queensland Australia
| | - Allan W Cripps
- b Menzies Health Institute Queensland , Southport , Queensland , Australia.,d School of Medicine, Griffith University , Southport , Queensland , Australia
| | - Amanda J Cox
- a School of Medical Science, Griffith University , Southport , Queensland , Australia.,b Menzies Health Institute Queensland , Southport , Queensland , Australia
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Abstract
Current opinion strongly links nutrition and health. Among nutrients, proteins, and peptides which are encrypted in their sequences and released during digestion could play a key role in improving health. These peptides have been claimed to be active on a wide spectrum of biological functions or diseases, including blood pressure and metabolic risk factors (coagulation, obesity, lipoprotein metabolism, and peroxidation), gut and neurological functions, immunity, cancer, dental health, and mineral metabolism. A majority of studies involved dairy peptides, but the properties of vegetal, animal, and sea products were also assessed. However, these allegations are mainly based on in vitro and experimental studies which are seldom confirmed in humans. This review focused on molecules which were tested in humans, and on the mechanisms explaining discrepancies between experimental and human studies.
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Affiliation(s)
| | - Saïd Bouhallab
- b STLO, UMR1253, INRA, Agrocamus Ouest , Rennes , France
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Nakamura K, Morishita S, Ono T, Murakoshi M, Sugiyama K, Kato H, Ikeda I, Nishino H. Lactoferrin interacts with bile acids and increases fecal cholesterol excretion in rats. Biochem Cell Biol 2017; 95:142-147. [DOI: 10.1139/bcb-2016-0052] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Lactoferrin (LF) is a multifunctional cationic protein (pI 8.2–8.9) in mammalian milk. We previously reported that enteric-LF prevented hypercholesterolemia and atherosclerosis in a diet-induced atherosclerosis model using Microminipig, although the underlying mechanisms remain unclear. Because LF is assumed to electrostatically interact with bile acids to inhibit intestinal cholesterol absorption, LF could promote cholesterol excretion. In this study, we assessed the interaction between LF and taurocholate in vitro, and the effect of LF on cholesterol excretion in rats. The binding rate of taurocholate to LF was significantly higher than that to transferrin (pI 5.2–6.3). When rats were administered a high-cholesterol diet (HCD) containing 5% LF, LF was detected using ELISA in the upper small intestine from 7.5 to 60 min after the administration. Rats were fed one of the following diets: control, HCD, or HCD + 5% LF for 21 days. Fecal neutral steroids and hepatic cholesterol levels in the HCD group were significantly higher than those in the control group. The addition of LF to a HCD significantly increased fecal neutral steroids levels (22% increase, p < 0.05) and reduced hepatic cholesterol levels (17% decrease, p < 0.05). These parameters were inversely correlated (R = −0.63, p < 0.05). These results suggest that LF promotes cholesterol excretion via interactions with bile acids.
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Affiliation(s)
- Kanae Nakamura
- Research and Development Headquarters, Lion Corporation, 100 Tajima, Odawara, Kanagawa 256-0811, Japan
| | - Satoru Morishita
- Research and Development Headquarters, Lion Corporation, 100 Tajima, Odawara, Kanagawa 256-0811, Japan
- “Food for Life”, Organization for Interdisciplinary Research Projects, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
| | - Tomoji Ono
- Research and Development Headquarters, Lion Corporation, 100 Tajima, Odawara, Kanagawa 256-0811, Japan
- Advanced Medical Research Center, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan
| | - Michiaki Murakoshi
- Research and Development Headquarters, Lion Corporation, 100 Tajima, Odawara, Kanagawa 256-0811, Japan
- Advanced Medical Research Center, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan
- Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto 602-0841, Japan
| | - Keikichi Sugiyama
- Research and Development Headquarters, Lion Corporation, 100 Tajima, Odawara, Kanagawa 256-0811, Japan
- Research Organization of Science and Engineering, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan
| | - Hisanori Kato
- “Food for Life”, Organization for Interdisciplinary Research Projects, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
| | - Ikuo Ikeda
- Laboratory of Food and Biomolecular Science, Department of Food Function and Health, Graduate School of Agricultural Science, Tohoku University, 1-1 Amamiya-machi, Tsutsumidori, Aoba-ku, Sendai, Miyagi 981-8555, Japan
| | - Hoyoku Nishino
- Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto 602-0841, Japan
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Mayeur S, Veilleux A, Pouliot Y, Lamarche B, Beaulieu JF, Hould FS, Richard D, Tchernof A, Levy E. Plasma Lactoferrin Levels Positively Correlate with Insulin Resistance despite an Inverse Association with Total Adiposity in Lean and Severely Obese Patients. PLoS One 2016; 11:e0166138. [PMID: 27902700 PMCID: PMC5130198 DOI: 10.1371/journal.pone.0166138] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Accepted: 10/24/2016] [Indexed: 01/16/2023] Open
Abstract
Context Lactoferrin (Lf) is an important protein found on mucosal surfaces, within neutrophils and various cells, and in biological fluids. It displays multiple functions, including iron-binding as well as antimicrobial, immunomodulatory and anti-inflammatory activities. Although Lf ingestion has been suggested to cause adiposity reduction in murine models and humans, its relationship with insulin resistance (IR) has not been studied thoroughly. Objective To establish the association between circulating Lf levels, glucose status and blood lipid/lipoprotein profile. Methods Two independent cohorts were examined: lean to moderately obese women admitted for gynecological surgery (n = 53) and severely obese subjects undergoing biliopancreatic diversion (n = 62). Results Although body mass index (BMI) and total body fat mass were negatively associated with Lf, IR (assessed by the HOMA-IR index) was positively and independently associated with plasma Lf concentrations of the first cohort of lean to moderately obese women. These observations were validated in the second cohort in view of the positive correlation between plasma Lf concentrations and the HOMA-IR index, but without a significant association with the body mass index (BMI) of severely obese subjects. In subsamples of severely obese subjects matched for sex, age and BMI, but with either relatively low (1.89 ± 0.73) or high (13.77 ± 8.81) IR states (according to HOMA-IR), higher plasma Lf levels were noted in insulin-resistant vs insulin-sensitive subjects (P<0.05). Finally, Lf levels were significantly higher in lean to moderately obese women than in severely obese subjects (P<0.05). Conclusion Our findings revealed that plasma Lf levels are strongly associated with IR independently of total adiposity, which suggests an intriguing Lf regulation mechanism in conditions of obesity and IR.
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Affiliation(s)
- Sylvain Mayeur
- Research Centre CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada
| | - Alain Veilleux
- Research Centre CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada
| | - Yves Pouliot
- Institute of Nutrition and Functional Foods (INAF), Université Laval, Quebec, Quebec, Canada
| | - Benoît Lamarche
- Institute of Nutrition and Functional Foods (INAF), Université Laval, Quebec, Quebec, Canada
| | - Jean-François Beaulieu
- Department of Anatomy and Cellular Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada
| | - Frédéric S. Hould
- Institut universitaire de cardiologie et de pneumologie de Québec, Quebec, Canada
| | - Denis Richard
- Institut universitaire de cardiologie et de pneumologie de Québec, Quebec, Canada
| | - André Tchernof
- Institute of Nutrition and Functional Foods (INAF), Université Laval, Quebec, Quebec, Canada
| | - Emile Levy
- Research Centre CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada
- Institute of Nutrition and Functional Foods (INAF), Université Laval, Quebec, Quebec, Canada
- Department of Nutrition, Université de Montréal, Montreal, Quebec, Canada
- * E-mail:
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Cox AJ, Watts AM, Zhang P, Williams LT, Cripps AW, West NP. Effects of short-term supplementation with bovine lactoferrin and/or immunoglobulins on body mass and metabolic measures: a randomised controlled trial. Int J Food Sci Nutr 2016; 68:219-226. [DOI: 10.1080/09637486.2016.1224230] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
- Amanda J. Cox
- Menzies Health Institute Queensland, Griffith University, QLD, Australia
- School of Medical Science, Griffith University, QLD, Australia
| | | | - Ping Zhang
- Menzies Health Institute Queensland, Griffith University, QLD, Australia
| | - Lauren T. Williams
- Menzies Health Institute Queensland, Griffith University, QLD, Australia
- School of Allied Health Sciences, Griffith University, QLD, Australia
| | - Allan W. Cripps
- Menzies Health Institute Queensland, Griffith University, QLD, Australia
- School of Medicine, Griffith University, QLD, Australia
| | - Nicholas P. West
- Menzies Health Institute Queensland, Griffith University, QLD, Australia
- School of Medical Science, Griffith University, QLD, Australia
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Otsuki K, Imai N. Effects of lactoferrin in 6 patients with refractory bacterial vaginosis. Biochem Cell Biol 2016; 95:31-33. [PMID: 28140620 DOI: 10.1139/bcb-2016-0051] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
We previously reported that lactoferrin (LF) could be effective for preventing preterm delivery and intrauterine infections, based on data derived from mice and rabbits. Here we describe 6 women with a history of multiple pregnancy losses or preterm delivery and refractory bacterial vaginosis, who received prebiotic LF therapy and delivered an infant normally. Five of the women were pregnant and one was not at the time of this study. The Ethics Committee at Showa University Hospital and Showa University Koto Toyosu Hospital approved the therapeutic protocol. Vaginal suppositories and oral prebiotic LF were administered to patients who were refractory to conventional treatment for vaginosis and had a history of late miscarriages and very early preterm delivery due to refractory vaginitis and chorioamnionitis. LF significantly improved the vaginal bacterial flora. Lactobacillus, which was detectable in the vaginas of all patients after one month of LF therapy, gradually became dominant. The findings from these 6 patients suggest that administering LF to humans could help prevent refractory vaginitis, cervical inflammation, and preterm delivery.
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Affiliation(s)
- Katsufumi Otsuki
- a Department of Obstetrics and Gynecology, Showa University Koto Toyosu Hospital, Koto-ku, Tokyo, Japan
| | - Noriaki Imai
- b Department of Obstetrics and Gynecology, Hachinohe City Hospital, Hachinohe, Aomori, Japan
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Nakamura F, Ishida Y, Aihara K, Sawada D, Ashida N, Sugawara T, Aoki Y, Takehara I, Takano K, Fujiwara S. Effect of fragmented Lactobacillus amylovorus CP1563 on lipid metabolism in overweight and mildly obese individuals: a randomized controlled trial. MICROBIAL ECOLOGY IN HEALTH AND DISEASE 2016; 27:30312. [PMID: 27221805 PMCID: PMC4879181 DOI: 10.3402/mehd.v27.30312] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/06/2015] [Revised: 04/20/2016] [Accepted: 04/21/2016] [Indexed: 12/25/2022]
Abstract
Background Previously, we showed that fragmented Lactobacillus amylovorus CP1563 (CP1563) functions as a dual agonist of peroxisome proliferator-activated receptor α and γ in vitro and in vivo. Objective Here, we examined the safety and effect of CP1563 ingestion on body fat in obese class I participants in a double-blinded, placebo-controlled, randomized clinical trial (RCT). Design In the RCT, 200 participants with a body mass index (BMI) of 25–30 kg/m2 consumed test beverages with or without 200 mg of CP1563 daily for 12 weeks. In total, 197 subjects completed the study without any adverse effects. Results Body fat percentage, whole body fat, and visceral fat were significantly decreased in the test group compared with the placebo group (p<0.001, p<0.001, and p<0.001, respectively). Triglycerides, total cholesterol, LDL-cholesterol, and diastolic blood pressure showed significant reductions in the test group compared with the placebo group (p<0.001, p<0.001, p<0.001, and p<0.001, respectively). Additionally, significant differences in the changes in blood glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), and uric acid were observed between the two groups (p<0.001, p=0.004, p<0.001, and p<0.001, respectively). Improvements in anthropometric measurements and markers were observed in obese class I subjects in the test group. Conclusions Daily consumption of beverages containing fragmented CP1563 for 12 weeks by obese class I subjects improved anthropometric measurements and markers related to lipid and glucose metabolism without any adverse effects. These results suggest that the consumption of foods containing fragmented CP1563 reduces body fat and prevents metabolic syndrome.
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Affiliation(s)
- Futoshi Nakamura
- Research & Development Center, Asahi Group Holdings, Ltd., Chuo-ku, Sagamihara-shi, Kanagawa, Japan
| | - Yu Ishida
- Research & Development Center, Asahi Group Holdings, Ltd., Chuo-ku, Sagamihara-shi, Kanagawa, Japan
| | - Kohtaro Aihara
- Research & Development Center, Asahi Group Holdings, Ltd., Chuo-ku, Sagamihara-shi, Kanagawa, Japan
| | - Daisuke Sawada
- Research & Development Center, Asahi Group Holdings, Ltd., Chuo-ku, Sagamihara-shi, Kanagawa, Japan
| | - Nobuhisa Ashida
- Research & Development Center, Asahi Group Holdings, Ltd., Chuo-ku, Sagamihara-shi, Kanagawa, Japan
| | - Tomonori Sugawara
- Research & Development Center, Asahi Group Holdings, Ltd., Chuo-ku, Sagamihara-shi, Kanagawa, Japan
| | - Yumeko Aoki
- Research & Development Center, Asahi Group Holdings, Ltd., Chuo-ku, Sagamihara-shi, Kanagawa, Japan
| | - Isao Takehara
- I-Food Service Division, Clinical Support Corporation, Chuo-ku, Sapporo, Hokkaido, Japan
| | - Kazuhiko Takano
- Medical Corporation Hokubukai Utsukushigaoka Hospital, Kiyota-ku, Sapporo, Hokkaido, Japan
| | - Shigeru Fujiwara
- Research & Development Center, Asahi Group Holdings, Ltd., Chuo-ku, Sagamihara-shi, Kanagawa, Japan;
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Mayeur S, Spahis S, Pouliot Y, Levy E. Lactoferrin, a Pleiotropic Protein in Health and Disease. Antioxid Redox Signal 2016; 24:813-36. [PMID: 26981846 DOI: 10.1089/ars.2015.6458] [Citation(s) in RCA: 115] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
SIGNIFICANCE Lactoferrin (Lf) is a nonheme iron-binding glycoprotein strongly expressed in human and bovine milk and it plays many functions during infancy such as iron homeostasis and defense against microorganisms. In humans, Lf is mainly expressed in mucosal epithelial and immune cells. Growing evidence suggests multiple physiological roles for Lf after weaning. RECENT ADVANCES The aim of this review is to highlight the recent advances concerning multifunctional Lf activities. CRITICAL ISSUES First, we will provide an overview of the mechanisms related to Lf intrinsic synthesis or intestinal absorption as well as its interaction with a wide spectrum of mammalian receptors and distribution in organs and cell types. Second, we will discuss the large variety of its physiological functions such as iron homeostasis, transportation, immune regulation, oxidative stress, inflammation, and apoptosis while specifying the mechanisms of action. Third, we will focus on its recent physiopathology implication in metabolic disorders, including obesity, type 2 diabetes, and cardiovascular diseases. Additional efforts are necessary before suggesting the potential use of Lf as a diagnostic marker or as a therapeutic tool. FUTURE DIRECTIONS The main sources of Lf in human cardiometabolic disorders should be clarified to identify new perspectives for future research and develop new strategies using Lf in therapeutics. Antioxid. Redox Signal. 24, 813-836.
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Affiliation(s)
- Sylvain Mayeur
- 1 Research Centre, CHU Ste-Justine, Université de Montréal , Montreal, Canada .,2 Institute of Nutraceuticals and Functional Foods (INAF) , Université Laval, Quebec, Canada
| | - Schohraya Spahis
- 1 Research Centre, CHU Ste-Justine, Université de Montréal , Montreal, Canada .,2 Institute of Nutraceuticals and Functional Foods (INAF) , Université Laval, Quebec, Canada .,3 Department of Nutrition, Université de Montréal , Montreal, Canada
| | - Yves Pouliot
- 3 Department of Nutrition, Université de Montréal , Montreal, Canada
| | - Emile Levy
- 1 Research Centre, CHU Ste-Justine, Université de Montréal , Montreal, Canada .,2 Institute of Nutraceuticals and Functional Foods (INAF) , Université Laval, Quebec, Canada .,3 Department of Nutrition, Université de Montréal , Montreal, Canada
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Sun J, Ren F, Xiong L, Zhao L, Guo H. Bovine lactoferrin suppresses high-fat diet induced obesity and modulates gut microbiota in C57BL/6J mice. J Funct Foods 2016. [DOI: 10.1016/j.jff.2016.01.022] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
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50
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Morimoto-Kobayashi Y, Ohara K, Ashigai H, Kanaya T, Koizumi K, Manabe F, Kaneko Y, Taniguchi Y, Katayama M, Kowatari Y, Kondo S. Matured hop extract reduces body fat in healthy overweight humans: a randomized, double-blind, placebo-controlled parallel group study. Nutr J 2016; 15:25. [PMID: 26960416 PMCID: PMC4784395 DOI: 10.1186/s12937-016-0144-2] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Accepted: 03/02/2016] [Indexed: 12/15/2022] Open
Abstract
Background Hops are the main components of beer that provide flavor and bitterness. Iso-α-acids, the bitter components of beer, have been reported to reduce body fat in humans, but the bitterness induced by effective doses of iso-α-acids precludes their acceptance as a nutrient. The matured hop bitter acids (MHBA) of oxidized hops appear to have a more pleasant bitterness compared to the sharper bitterness of iso-α-acids. While there has been little information concerning the identity of the MHBA compounds and their physiological effects, MHBA was recently found to be primarily composed of oxides derived from α-acids, and structurally similar to iso-α-acids. Here, we investigated the effects of matured hop extract (MHE) containing MHBA on reducing abdominal body fat in healthy subjects with a body mass index (BMI) of 25 to below 30 kg/m2, classified as “obese level 1” in Japan or as “overweight” by the WHO. Trial design A randomized, double-blind, placebo-controlled parallel group study. Methods Two hundred subjects (male and female aged 20 to below 65 years with a BMI of 25 or more and less than 30 kg/m2) were randomly assigned to two groups. During a 12-week ingestion period, the subjects in each group ingested daily 350 mL of test-beverage, either containing MHE (with 35 mg MHBA), i.e. the namely active beverage, or a placebo beverage without MHE. The primary endpoint was reduction of the abdominal fat area as determined by CT scanning after continual ingestion of MHE for 12 weeks. Results Compared to the placebo group, a significant reduction was observed in the visceral fat area after 8 and 12 w, and in the total fat area after 12 w in the active group. There was also a concomitant decrease in body fat ratio in the active group compared to the placebo group. No adverse events related to the test beverages or clinically relevant abnormal changes in the circulatory, blood and urine parameters were observed in either group. Conclusions The present study suggests that continual ingestion of MHE safely reduces body fat, particularly the abdominal visceral fat of healthy overweight subjects. Trial registration UMIN-CTR UMIN000014185 Electronic supplementary material The online version of this article (doi:10.1186/s12937-016-0144-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yumie Morimoto-Kobayashi
- Research Laboratories for Health Science and Food Technologies, Kirin Company, Ltd, 1-13-5, Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
| | - Kazuaki Ohara
- Research Laboratories for Health Science and Food Technologies, Kirin Company, Ltd, 1-13-5, Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
| | - Hiroshi Ashigai
- Research Laboratories for Health Science and Food Technologies, Kirin Company, Ltd, 1-13-5, Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
| | - Tomoka Kanaya
- Research Laboratories for Health Science and Food Technologies, Kirin Company, Ltd, 1-13-5, Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
| | - Kumiko Koizumi
- Research Laboratories for Health Science and Food Technologies, Kirin Company, Ltd, 1-13-5, Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
| | - Fumitoshi Manabe
- Research Laboratories for Health Science and Food Technologies, Kirin Company, Ltd, 1-13-5, Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
| | - Yuji Kaneko
- Research Laboratories for Health Science and Food Technologies, Kirin Company, Ltd, 1-13-5, Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
| | - Yoshimasa Taniguchi
- Central Laboratories for Key Technologies, Kirin Company, Ltd, 1-13-5, Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
| | - Mikio Katayama
- Research Laboratories for Health Science and Food Technologies, Kirin Company, Ltd, 1-13-5, Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
| | - Yasuyuki Kowatari
- Ueno Clinic, Aiseikai Public Interest Incorporated Foundation, 2-18-6, Higashiueno, Taito-ku, Tokyo, 110-0015, Japan.
| | - Sumio Kondo
- Fukushima Healthcare Center, Kensyokai Medical Corporation, 2-12-16, Tamakawa, Fukushima-ku, Osaka, 553-0004, Japan.
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