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1
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Balbuena-Pecino S, Riera-Heredia N, Sánchez-Moya A, Perelló-Amorós M, Gutiérrez J, Capilla E, Navarro I. Screening the effects of phytoestrogens on lipid metabolism in primary cultured adipocytes from rainbow trout (Oncorhynchus mykiss) and gilthead sea bream (Sparus aurata). FISH PHYSIOLOGY AND BIOCHEMISTRY 2025; 51:71. [PMID: 40131537 PMCID: PMC11937063 DOI: 10.1007/s10695-025-01483-1] [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] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 03/05/2025] [Indexed: 03/27/2025]
Abstract
Aquafeed formulation has progressively reduced its dependence on fish-derived ingredients over the past decades. Plant-based substitutes have been a major focus, with soybean meal and its derivatives leading the way. However, many plants contain phytoestrogens, which may affect fish physiology. This study aimed to assess in vitro the effects of genistein (GE), daidzein (DZN), glycitein (GLY), and coumestrol (COU) on the lipid metabolism of rainbow trout (Oncorhynchus mykiss) and gilthead sea bream (Sparus aurata). Primary cultured adipocytes were incubated with these phytoestrogens, along with 17β-estradiol, at two doses each (1, 10, or 100 μM). The 100 μM dose of GE and DZN decreased adipocyte viability, and mainly enhanced lipid accumulation in both species, suggesting a hypertrophic condition. However, the reduction in adipocyte number and lipid content with 100 μM DZN in rainbow trout indicated a limiting effect on adipose tissue growth in this species. Interestingly, COU significantly increased cell viability in gilthead sea bream, potentially leading to hyperplastic growth, a more favorable metabolic state. In that species, which proved to be more phytoestrogens-sensitive, lipoprotein lipase was generally downregulated upon treatments. Moreover, 10 µM GE significantly decreased the mRNA levels of fatty acid transport protein 1 and fatty acid synthase, and increased those of fatty acid binding protein 1, suggesting an acceleration of the differentiation process compared to the control cells. This work provides new insights into how dietary phytoestrogens modulate fish lipid metabolism and supports that their presence in plant protein feedstuffs can potentially affect fish health and production performance.
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Affiliation(s)
- Sara Balbuena-Pecino
- Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028, Barcelona, Spain
| | - Natàlia Riera-Heredia
- Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028, Barcelona, Spain
| | - Albert Sánchez-Moya
- Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028, Barcelona, Spain
| | | | - Joaquim Gutiérrez
- Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028, Barcelona, Spain
| | - Encarnación Capilla
- Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028, Barcelona, Spain
| | - Isabel Navarro
- Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028, Barcelona, Spain.
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2
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Le Roux CE, Farthing AL, Lucas EK. Dietary phytoestrogens recalibrate socioemotional behavior in C57Bl/6J mice in a sex- and timing-dependent manner. Horm Behav 2025; 168:105678. [PMID: 39826371 PMCID: PMC11830535 DOI: 10.1016/j.yhbeh.2025.105678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Revised: 01/05/2025] [Accepted: 01/14/2025] [Indexed: 01/22/2025]
Abstract
Estrogens are potent regulators of socioemotional behavior across species. Ubiquitous in human and animal diets, plant-derived phytoestrogens (PE) bind estrogen receptors. While prior work has examined the impact of PE exposure on socioemotional behavior, findings are inconsistent across studies. To investigate whether the timing of PE diet initiation may govern differential behavioral effects, we compared the impacts of PE-free (<20 mg/kg) versus PE-rich (810 mg/kg) diet exposure across the lifetime versus acutely in adulthood. Reproductive physiology was assessed through age at puberty onset and gonadal size. In adulthood, all mice underwent a behavioral battery consisting of the open field, elevated plus maze, and social interaction tests, followed by assessment of emotional memory dynamics with cued threat conditioning, extinction, recall, and renewal. Lifetime PE exposure delayed puberty onset and increased adult gonadal size selectively in males, whereas both lifetime and adult-only PE exposure decreased adult body weight in both sexes. In males, adult-only exposure increased open-arm avoidance in the elevated plus maze but enhanced threat memory extinction. In females, lifetime PE exposure increased open-arm avoidance, reduced sociability, and impaired threat memory extinction. Interestingly, lifetime PE exposure increased the context-dependent renewal of threat memory in both sexes. These findings demonstrate sex- and timing-dependent effects of PE exposure. Male lifetime PE exposure impacts reproductive measures with limited behavioral effects, whereas female lifetime exposure broadly impairs socioemotional behavior. Conversely, adult-only PE exposure altered behavior in males with limited impact in females. This study highlights the importance of diet composition, exposure period, and sex in rodent behavioral studies.
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Affiliation(s)
- Cameron E Le Roux
- Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Amy L Farthing
- Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA
| | - Elizabeth K Lucas
- Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; Department of Psychiatry & Behavioral Neurobiology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
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3
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Meyer Z, Soukup ST, Lubs A, Ohde D, Walz C, Schoen J, Willenberg HS, Hoeflich A, Brenmoehl J. Impact of Dietary Isoflavones in Standard Chow on Reproductive Development in Juvenile and Adult Female Mice with Different Metabolic Phenotypes. Nutrients 2024; 16:2697. [PMID: 39203833 PMCID: PMC11357413 DOI: 10.3390/nu16162697] [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: 07/03/2024] [Revised: 08/09/2024] [Accepted: 08/12/2024] [Indexed: 09/03/2024] Open
Abstract
Two factors influencing female reproduction have been repeatedly studied in different animal species and humans, namely, 1. secondary plant compounds, especially phytoestrogens (mainly isoflavones (IFs)), and 2. the physical constitution/metabolic phenotype (e.g., obesity). So far, these research results have only been considered separately. In this study, we investigated the influence on reproduction of both phytochemicals, mainly dietary IFs, and the metabolic phenotype represented by three mouse models considered as three distinct genetic groups (a control group, a mouse model with high metabolic activity, and a mouse line with obese body weight). The IF content in different investigated standard chows with similar macronutrient profiles varied significantly (p < 0.005), leading to high mean total plasma IF levels of up to 5.8 µmol/L in juvenile and 6.7 µmol/L in adult female mice. Reproductive performance was only slightly affected; only an IF dose-dependent effect on gestation length was observed in all genetic groups, as well as an effect on pregnancy rate in obese mice. Dietary IF exposure, however, caused earlier onset of vaginal opening by 4-10 days in juvenile mice (p < 0.05), dependent on the genetic group, resulting in a slight acceleration of sexual maturation in the already precocious obese model and to a strong earlier maturation in the otherwise late-maturing sporty model, bred for high treadmill performance. Therefore, our results may help to draw the missing line between the effect of dietary secondary plant constituents, such as IFs, and metabolic phenotype on sexual development.
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Affiliation(s)
- Zianka Meyer
- Working Group Endocrinology of Farm Animals, Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
| | - Sebastian T. Soukup
- Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institute, Federal Research Institute of Nutrition and Food, Haid-und-Neu-Straße 9, 76131 Karlsruhe, Germany
| | - Anna Lubs
- Working Group Cell Physiology & Reproduction, Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
| | - Daniela Ohde
- Working Group Endocrinology of Farm Animals, Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
| | - Christina Walz
- Working Group Endocrinology of Farm Animals, Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
| | - Jennifer Schoen
- Working Group Cell Physiology & Reproduction, Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
- Reproduction Biology Department, Leibniz Institute for Zoo and Wildlife Research IZW, Alfred-Kowalke-Straße 17, 10315 Berlin, Germany
| | - Holger S. Willenberg
- Center for Internal Medicine, Section of Endocrinology and Metabolic Diseases, University Medicine Rostock, Ernst-Heydemann-Str. 6, 18057 Rostock, Germany
| | - Andreas Hoeflich
- Working Group Endocrinology of Farm Animals, Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
| | - Julia Brenmoehl
- Working Group Endocrinology of Farm Animals, Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
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4
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Zhao XY, Wang JQ, Neely GG, Shi YC, Wang QP. Natural compounds as obesity pharmacotherapies. Phytother Res 2024; 38:797-838. [PMID: 38083970 DOI: 10.1002/ptr.8083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Revised: 10/20/2023] [Accepted: 11/22/2023] [Indexed: 02/15/2024]
Abstract
Obesity has become a serious global public health problem, affecting over 988 million people worldwide. Nevertheless, current pharmacotherapies have proven inadequate. Natural compounds have garnered significant attention due to their potential antiobesity effects. Over the past three decades, ca. 50 natural compounds have been evaluated for the preventive and/or therapeutic effects on obesity in animals and humans. However, variations in the antiobesity efficacies among these natural compounds have been substantial, owing to differences in experimental designs, including variations in animal models, dosages, treatment durations, and administration methods. The feasibility of employing these natural compounds as pharmacotherapies for obesity remained uncertain. In this review, we systematically summarized the antiobesity efficacy and mechanisms of action of each natural compound in animal models. This comprehensive review furnishes valuable insights for the development of antiobesity medications based on natural compounds.
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Affiliation(s)
- Xin-Yuan Zhao
- Laboratory of Metabolism and Aging, School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China
| | - Ji-Qiu Wang
- Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - G Gregory Neely
- The Dr. John and Anne Chong Laboratory for Functional Genomics, Charles Perkins Centre and School of Life & Environmental Sciences, The University of Sydney, Sydney, NSW, Australia
| | - Yan-Chuan Shi
- Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW, Australia
- St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Qiao-Ping Wang
- Laboratory of Metabolism and Aging, School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China
- Medical Center for Comprehensive Weight Control, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Diabetology, Guangzhou Key Laboratory of Mechanistic and Translational Obesity Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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5
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Xiang J, Mlambo R, Dube P, Machona O, Shaw I, Seid Y, He Y, Luo M, Hong T, He B, Zhou W, Tan S. The obesogenic side of Genistein. Front Endocrinol (Lausanne) 2023; 14:1308341. [PMID: 38098865 PMCID: PMC10720314 DOI: 10.3389/fendo.2023.1308341] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Accepted: 11/16/2023] [Indexed: 12/17/2023] Open
Abstract
Genistein (GN) has been highly recommended for its medicinal properties like anticancer, antidiabetic, antihyperlipidemic, antiviral, and antioxidant activities among others. Recently, scientists realized that Genistein is an endocrine disruptor. It is an obesogen that interferes with the endocrine system causing obesity through many mechanisms like inducing adipocyte differentiation, lipid accumulation, and transformation of some stem cells into adipocytes (bone marrow mesenchymal stem cells for example) in vitro. Animal studies show that GN upregulates genes associated with adipogenesis like CCAAT/enhancer binding protein alpha (Cebpα), CCAAT/enhancer binding protein beta (Cebpβ), and PPARγ. In silico studies reveal a strong binding affinity for estrogen receptors. All these findings were contingent on concentration and tissues. It is beyond dispute that obesity is one of the most frustrating medical conditions under the sun. The pathophysiology of this disease was first attributed to a high-calorie diet and lack of physical activity. However, studies proved that these two factors are not enough to account for obesity in both children and adults. This mini review highlights how Genistein interaction with the peroxisome proliferator-activated receptor gamma protein can cause obesity.
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Affiliation(s)
- Jia Xiang
- Academician Workstation, Changsha Medical University, Changsha, China
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, China
| | - Ronald Mlambo
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, China
| | - Progress Dube
- Simon Mazorodze School of Medical and Health Sciences, Great Zimbabwe University, Masvingo, Zimbabwe
| | - Oleen Machona
- Simon Mazorodze School of Medical and Health Sciences, Great Zimbabwe University, Masvingo, Zimbabwe
| | - Ibrahim Shaw
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, China
| | - Yimer Seid
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, China
| | - Yongju He
- School of Materials Science and Engineering, Central South University, Changsha, Hunan, China
| | - Min Luo
- Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Tingting Hong
- School of Pharmacy, Changzhou University, Changzhou, Jiangsu, China
| | - Binsheng He
- Academician Workstation, Changsha Medical University, Changsha, China
| | - Wenhu Zhou
- Academician Workstation, Changsha Medical University, Changsha, China
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, China
| | - Songwen Tan
- Academician Workstation, Changsha Medical University, Changsha, China
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, China
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6
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Jin X, Perrella SL, Lai CT, Taylor NL, Geddes DT. Oestrogens and progesterone in human milk and their effects on infant health outcomes: A narrative review. Food Chem 2023; 424:136375. [PMID: 37209436 DOI: 10.1016/j.foodchem.2023.136375] [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: 02/10/2023] [Revised: 04/26/2023] [Accepted: 05/11/2023] [Indexed: 05/22/2023]
Abstract
Human milk (HM) is a complex biological system that contains a wide range of bioactive components including oestrogens and progesterone. Whilst maternal oestrogens and progesterone concentrations drop rapidly after birth, they remain detectable in HM across lactation. Phytoestrogens and mycoestrogens, which are produced by plants and fungi, are also present in HM and can interact with oestrogen receptors to interfere with normal hormone functions. Despite the potential impact of HM oestrogens and progesterone on the infant, limited research has addressed their impact on the growth and health of breastfed infants. Furthermore, it is important to comprehensively understand the factors that contribute to these hormone levels in HM, in order to establish effective intervention strategies. In this review, we have summarized the concentrations of naturally occurring oestrogens and progesterone in HM from both endogenous and exogenous sources and discussed both maternal factors impacting HM levels and relationships with infant growth.
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Affiliation(s)
- Xuehua Jin
- School of Molecular Sciences, The University of Western Australia, Crawley 6009, WA, Australia
| | - Sharon Lisa Perrella
- School of Molecular Sciences, The University of Western Australia, Crawley 6009, WA, Australia
| | - Ching Tat Lai
- School of Molecular Sciences, The University of Western Australia, Crawley 6009, WA, Australia
| | - Nicolas Lyndon Taylor
- School of Molecular Sciences, The University of Western Australia, Crawley 6009, WA, Australia
| | - Donna Tracy Geddes
- School of Molecular Sciences, The University of Western Australia, Crawley 6009, WA, Australia.
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7
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Simmen FA, Pabona JMP, Al-Dwairi A, Alhallak I, Montales MTE, Simmen RCM. Malic Enzyme 1 (ME1) Promotes Adiposity and Hepatic Steatosis and Induces Circulating Insulin and Leptin in Obese Female Mice. Int J Mol Sci 2023; 24:ijms24076613. [PMID: 37047583 PMCID: PMC10095602 DOI: 10.3390/ijms24076613] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 03/21/2023] [Accepted: 03/29/2023] [Indexed: 04/05/2023] Open
Abstract
Malic Enzyme 1 (ME1) supports lipogenesis, cholesterol synthesis, and cellular redox potential by catalyzing the decarboxylation of L-malate to pyruvate, and the concomitant reduction of NADP to NADPH. We examined the contribution of ME1 to the development of obesity by provision of an obesogenic diet to C57BL/6 wild type (WT) and MOD-1 (lack ME1 protein) female mice. Adiposity, serum hormone levels, and adipose, mammary gland, liver, and small intestine gene expression patterns were compared between experimental groups after 10 weeks on a diet. Relative to WT female mice, MOD-1 female mice exhibited lower body weights and less adiposity; decreased concentrations of insulin, leptin, and estrogen; higher concentrations of adiponectin and progesterone; smaller-sized mammary gland adipocytes; and reduced hepatosteatosis. MOD-1 mice had diminished expression of Lep gene in abdominal fat; Lep, Pparg, Klf9, and Acaca genes in mammary glands; Pparg and Cdkn1a genes in liver; and Tlr9 and Ffar3 genes in the small intestine. By contrast, liver expression of Cdkn2a and Lepr genes was augmented in MOD-1, relative to WT mice. Results document an integrative role for ME1 in development of female obesity, suggest novel linkages with specific pathways/genes, and further support the therapeutic targeting of ME1 for obesity, diabetes, and fatty liver disease.
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Affiliation(s)
- Frank A. Simmen
- Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
- The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - John Mark P. Pabona
- Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Ahmed Al-Dwairi
- Department of Physiology and Biochemistry, College of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Iad Alhallak
- Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Maria Theresa E. Montales
- Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Rosalia C. M. Simmen
- Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
- The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
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8
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Is Hormone Replacement Therapy a Risk Factor or a Therapeutic Option for Alzheimer's Disease? Int J Mol Sci 2023; 24:ijms24043205. [PMID: 36834617 PMCID: PMC9964432 DOI: 10.3390/ijms24043205] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 01/21/2023] [Accepted: 01/23/2023] [Indexed: 02/07/2023] Open
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for more than half of all dementia cases in the elderly. Interestingly, the clinical manifestations of AD disproportionately affect women, comprising two thirds of all AD cases. Although the underlying mechanisms for these sex differences are not fully elucidated, evidence suggests a link between menopause and a higher risk of developing AD, highlighting the critical role of decreased estrogen levels in AD pathogenesis. The focus of this review is to evaluate clinical and observational studies in women, which have investigated the impact of estrogens on cognition or attempted to answer the prevailing question regarding the use of hormone replacement therapy (HRT) as a preventive or therapeutic option for AD. The articles were retrieved through a systematic review of the databases: OVID, SCOPUS, and PubMed (keywords "memory", "dementia," "cognition," "Alzheimer's disease", "estrogen", "estradiol", "hormone therapy" and "hormone replacement therapy" and by searching reference sections from identified studies and review articles). This review presents the relevant literature available on the topic and discusses the mechanisms, effects, and hypotheses that contribute to the conflicting findings of HRT in the prevention and treatment of age-related cognitive deficits and AD. The literature suggests that estrogens have a clear role in modulating dementia risk, with reliable evidence showing that HRT can have both a beneficial and a deleterious effect. Importantly, recommendation for the use of HRT should consider the age of initiation and baseline characteristics, such as genotype and cardiovascular health, as well as the dosage, formulation, and duration of treatment until the risk factors that modulate the effects of HRT can be more thoroughly investigated or progress in the development of alternative treatments can be made.
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9
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Kladnicka I, Bludovska M, Plavinova I, Muller L, Mullerova D. Obesogens in Foods. Biomolecules 2022; 12:biom12050680. [PMID: 35625608 PMCID: PMC9138445 DOI: 10.3390/biom12050680] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 05/03/2022] [Accepted: 05/06/2022] [Indexed: 02/07/2023] Open
Abstract
Obesogens, as environmental endocrine-disrupting chemicals, are supposed to have had an impact on the prevalence of rising obesity around the world over the last forty years. These chemicals are probably able to contribute not only to the development of obesity and metabolic disturbances in individuals, but also in their progeny, having the capability to epigenetically reprogram genetically inherited set-up points for body weight and body composition control during critical periods of development, such as fetal, early life, and puberty. In individuals, they may act on myriads of neuro-endocrine–immune metabolic regulatory pathways, leading to pathophysiological consequences in adipogenesis, lipogenesis, lipolysis, immunity, the influencing of central appetite and energy expenditure regulations, changes in gut microbiota–intestine functioning, and many other processes. Evidence-based medical data have recently brought much more convincing data about associations of particular chemicals and the probability of the raised risk of developing obesity. Foods are the main source of obesogens. Some obesogens occur naturally in food, but most are environmental chemicals, entering food as a foreign substance, whether in the form of contaminants or additives, and they are used in a large amount in highly processed food. This review article contributes to a better overview of obesogens, their occurrence in foods, and their impact on the human organism.
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Affiliation(s)
- Iva Kladnicka
- Department of Public Health and Preventive Medicine, Faculty of Medicine in Pilsen, Charles University, 301 00 Pilsen, Czech Republic; (M.B.); (I.P.); (D.M.)
- Department of Cybernetics, European Centre of Excellence New Technologies for the Information Society, University of West Bohemia, 301 00 Pilsen, Czech Republic;
- Correspondence: ; Tel.: +420-377-593-193
| | - Monika Bludovska
- Department of Public Health and Preventive Medicine, Faculty of Medicine in Pilsen, Charles University, 301 00 Pilsen, Czech Republic; (M.B.); (I.P.); (D.M.)
- Institute of Pharmacology and Toxicology, Faculty of Medicine in Pilsen, Charles University, 301 00 Pilsen, Czech Republic
| | - Iveta Plavinova
- Department of Public Health and Preventive Medicine, Faculty of Medicine in Pilsen, Charles University, 301 00 Pilsen, Czech Republic; (M.B.); (I.P.); (D.M.)
| | - Ludek Muller
- Department of Cybernetics, European Centre of Excellence New Technologies for the Information Society, University of West Bohemia, 301 00 Pilsen, Czech Republic;
| | - Dana Mullerova
- Department of Public Health and Preventive Medicine, Faculty of Medicine in Pilsen, Charles University, 301 00 Pilsen, Czech Republic; (M.B.); (I.P.); (D.M.)
- Department of Cybernetics, European Centre of Excellence New Technologies for the Information Society, University of West Bohemia, 301 00 Pilsen, Czech Republic;
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10
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Li S, Zhou L, Zhang Q, Yu M, Xiao X. Genistein improves glucose metabolism and promotes adipose tissue browning through modulating gut microbiota in mice. Food Funct 2022; 13:11715-11732. [DOI: 10.1039/d2fo01973f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Genistein improves glucose metabolism and promotes adipose tissue browning through modulating gut microbiota in mice.
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Affiliation(s)
- Shunhua Li
- Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Liyuan Zhou
- Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Qian Zhang
- Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Miao Yu
- Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Xinhua Xiao
- Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
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11
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Rato L, Sousa ACA. The Impact of Endocrine-Disrupting Chemicals in Male Fertility: Focus on the Action of Obesogens. J Xenobiot 2021; 11:163-196. [PMID: 34940512 PMCID: PMC8709303 DOI: 10.3390/jox11040012] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 11/12/2021] [Accepted: 11/23/2021] [Indexed: 12/11/2022] Open
Abstract
The current scenario of male infertility is not yet fully elucidated; however, there is increasing evidence that it is associated with the widespread exposure to endocrine-disrupting chemicals (EDCs), and in particular to obesogens. These compounds interfere with hormones involved in the regulation of metabolism and are associated with weight gain, being also able to change the functioning of the male reproductive axis and, consequently, the testicular physiology and metabolism that are pivotal for spermatogenesis. The disruption of these tightly regulated metabolic pathways leads to adverse reproductive outcomes. The permanent exposure to obesogens has raised serious health concerns. Evidence suggests that obesogens are one of the leading causes of the marked decline of male fertility and key players in shaping the future health outcomes not only for those who are directly exposed but also for upcoming generations. In addition to the changes that lead to inefficient functioning of the male gametes, obesogens induce alterations that are “imprinted” on the genes of the male gametes, establishing a link between generations and contributing to the transmission of defects. Unveiling the molecular mechanisms by which obesogens induce toxicity that may end-up in epigenetic modifications is imperative. This review describes and discusses the suggested molecular targets and potential mechanisms for obesogenic–disrupting chemicals and the subsequent effects on male reproductive health.
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Affiliation(s)
- Luís Rato
- Health School of the Polytechnic Institute of Guarda, 6300-035 Guarda, Portugal
- Correspondence: (L.R.); (A.C.A.S.)
| | - Ana C. A. Sousa
- Department of Biology, School of Science and Technology, University of Évora, 7006-554 Évora, Portugal
- Comprehensive Health Research Centre (CHRC), University of Évora, 7000-671 Évora, Portugal
- Correspondence: (L.R.); (A.C.A.S.)
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Asbaghi O, Ashtary-Larky D, Mousa A, Rezaei Kelishadi M, Moosavian SP. The Effects of Soy Products on Cardiovascular Risk Factors in Patients with Type 2 Diabetes: A Systematic Review and Meta-analysis of Clinical Trials. Adv Nutr 2021; 13:S2161-8313(22)00072-2. [PMID: 34591084 PMCID: PMC8970819 DOI: 10.1093/advances/nmab121] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Previous studies have suggested that soy products may be beneficial for cardiometabolic health, but current evidence regarding their effects in type 2 diabetes mellitus (T2DM) remain unclear. The aim of this systematic review and meta-analysis was to determine the impact of soy product consumption on cardiovascular risk factors in patients with T2DM. PubMed, Scopus, Embase, and the Cochrane library were systematically searched from inception to March 2021 using relevant keywords. All randomized controlled trials (RCTs) investigating the effects of soy product consumption on cardiovascular risk factors in patients with T2DM were included. Meta-analysis was performed using random-effects models and subgroup analysis was performed to explore variations by dose and baseline risk profile. A total of 22 trials with 867 participants were included in this meta-analysis. Soy product consumption led to a significant reduction in serum concentrations of triglycerides (TG) (WMD: -24.73 mg/dL; 95% CI: -37.49, -11.97), total cholesterol (TC) (WMD: -9.84 mg/dL; 95% CI: -15.07, -4.61), low density lipoprotein (LDL) cholesterol (WMD: -6.94 mg/dL; 95% CI: -11.71, -2.17) and C-reactive protein (CRP) (WMD: -1.27 mg/L; 95% CI: -2.39, -0.16). In contrast, soy products had no effect on high density lipoprotein (HDL) cholesterol, fasting blood sugar (FBS), fasting insulin, hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), systolic and diastolic blood pressure (SBP/DBP) or body mass index (BMI) (all P ≥ 0.05). In subgroup analyses, there was a significant reduction in FBS after soy consumption in patients with elevated baseline FBS (>126 mg/dL) and in those who received higher doses of soy intake (>30 g/d). Moreover, soy products decreased SBP in patients with baseline hypertension (>135 mmHg). Our meta-analysis suggests that soy product consumption may improve cardiovascular parameters in patients with T2DM, particularly in individuals with poor baseline risk profiles. However, larger studies with longer durations and improved methodological quality are needed before firm conclusions can be reached.
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Affiliation(s)
- Omid Asbaghi
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Damoon Ashtary-Larky
- Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Aya Mousa
- Monash Centre for Health Research and Implementation (MCHRI), School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Mahnaz Rezaei Kelishadi
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
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Leis K, Kulczyńska A, Racinowski M, Kaczor P, Gołębiewski J, Januszko-Giergielewicz B. Genistein–a supplement improving efficiency of the human body: A review. Sci Sports 2021. [DOI: 10.1016/j.scispo.2020.08.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Early Postnatal Genistein Administration Affects Mice Metabolism and Reproduction in a Sexually Dimorphic Way. Metabolites 2021; 11:metabo11070449. [PMID: 34357343 PMCID: PMC8303179 DOI: 10.3390/metabo11070449] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 07/04/2021] [Accepted: 07/07/2021] [Indexed: 12/30/2022] Open
Abstract
The phytoestrogen genistein (GEN) may interfere with permanent morphological changes in the brain circuits sensitive to estrogen. Due to the frequent use of soy milk in the neonatal diet, we aimed to study the effects of early GEN exposure on some physiological and reproductive parameters. Mice of both sexes from PND1 to PND8 were treated with GEN (50 mg/kg body weight, comparable to the exposure level in babies fed with soy-based formulas). When adult, we observed, in GEN-treated females, an advanced pubertal onset and an altered estrous cycle, and, in males, a decrease of testicle weight and fecal testosterone concentration. Furthermore, we observed an increase in body weight and altered plasma concentrations of metabolic hormones (leptin, ghrelin, triiodothyronine) limited to adult females. Exposure to GEN significantly altered kisspeptin and POMC immunoreactivity only in females and orexin immunoreactivity in both sexes. In conclusion, early postnatal exposure of mice to GEN determines long-term sex-specific organizational effects. It impairs the reproductive system and has an obesogenic effect only in females, which is probably due to the alterations of neuroendocrine circuits controlling metabolism; thus GEN, should be classified as a metabolism disrupting chemical.
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Oliveira FRK, Gustavo AFSE, Gonçalves RB, Bolfi F, Mendes AL, Nunes-Nogueira VDS. Association between a soy-based infant diet and the onset of puberty: A systematic review and meta-analysis. PLoS One 2021; 16:e0251241. [PMID: 34003856 PMCID: PMC8130953 DOI: 10.1371/journal.pone.0251241] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 04/23/2021] [Indexed: 11/28/2022] Open
Abstract
The objective of this systematic review was to evaluate the association between a soy-based infant diet and the onset of puberty. We included studies in which children were fed a soy-based diet, and we compared them with those who were not. The primary outcomes were the onset of puberty in girls (thelarche, pubarche, and menarche age), boys (pubarche, voice change, testicular and penis enlargement age), and both (risk of delayed and precocious puberty [PP]). Search strategies were performed in PubMed, Embase, LILACS, and CENTRAL databases. Two reviewers selected eligible studies, assessed the risk of bias, and extracted data from the included studies. The odds ratio (OR) and mean difference (MD) were calculated with a 95% confidence interval (CI) as a measure of the association between soy consumption and outcomes. We used a random-effects model to pool results across studies and the Grading of Recommendations Assessment, Development, and Evaluation to evaluate the certainty of evidence. We included eight studies in which 598 children consumed a soy-based diet but 2957 did not. The primary outcomes that could be plotted in the meta-analysis were the risk of PP and age at menarche. There was no statistical difference between groups for PP (OR: 0.51, 95% CI: 0.09 to 2.94, 3 studies, 206 participants, low certainty of evidence). No between-group difference was observed in menarche age (MD 0.14 years, 95% CI -0.16 to 0.45, 3 studies, 605 children, low certainty of evidence). One study presented this outcome in terms of median and interquartile range, and although the onset of menarche was marginally increased in girls who received a soy-based diet, the reported age was within the normal age range for menarche. We did not find any association between a soy-based infant diet and the onset of puberty in boys or girls. Trial Registration: PROSPERO registration: CRD42018088902.
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Affiliation(s)
- Flávia Ramos Kazan Oliveira
- Department of Internal Medicine, São Paulo State University (UNESP), Medical School, Botucatu, Sao Paulo, Brazil
| | - Ana Flora Silva e Gustavo
- Department of Internal Medicine, São Paulo State University (UNESP), Medical School, Botucatu, Sao Paulo, Brazil
| | - Renan Braga Gonçalves
- Department of Internal Medicine, São Paulo State University (UNESP), Medical School, Botucatu, Sao Paulo, Brazil
| | - Fernanda Bolfi
- Department of Internal Medicine, São Paulo State University (UNESP), Medical School, Botucatu, Sao Paulo, Brazil
| | - Adriana Lúcia Mendes
- Department of Internal Medicine, São Paulo State University (UNESP), Medical School, Botucatu, Sao Paulo, Brazil
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Basson AR, Ahmed S, Almutairi R, Seo B, Cominelli F. Regulation of Intestinal Inflammation by Soybean and Soy-Derived Compounds. Foods 2021; 10:foods10040774. [PMID: 33916612 PMCID: PMC8066255 DOI: 10.3390/foods10040774] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 03/30/2021] [Accepted: 04/02/2021] [Indexed: 02/06/2023] Open
Abstract
Environmental factors, particularly diet, are considered central to the pathogenesis of the inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis. In particular, the Westernization of diet, characterized by high intake of animal protein, saturated fat, and refined carbohydrates, has been shown to contribute to the development and progression of IBD. During the last decade, soybean, as well as soy-derived bioactive compounds (e.g., isoflavones, phytosterols, Bowman-Birk inhibitors) have been increasingly investigated because of their anti-inflammatory properties in animal models of IBD. Herein we provide a scoping review of the most studied disease mechanisms associated with disease induction and progression in IBD rodent models after feeding of either the whole food or a bioactive present in soybean.
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Affiliation(s)
- Abigail Raffner Basson
- Division of Gastroenterology & Liver Diseases, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA;
- Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA; (S.A.); (B.S.)
- Correspondence:
| | - Saleh Ahmed
- Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA; (S.A.); (B.S.)
| | - Rawan Almutairi
- Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA;
| | - Brian Seo
- Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA; (S.A.); (B.S.)
| | - Fabio Cominelli
- Division of Gastroenterology & Liver Diseases, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA;
- Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA; (S.A.); (B.S.)
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Exercise and/or Genistein Treatment Impact Gut Microbiota and Inflammation after 12 Weeks on a High-Fat, High-Sugar Diet in C57BL/6 Mice. Nutrients 2020; 12:nu12113410. [PMID: 33172007 PMCID: PMC7694625 DOI: 10.3390/nu12113410] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 10/30/2020] [Accepted: 11/02/2020] [Indexed: 02/07/2023] Open
Abstract
Genistein (Gen) and exercise (Exe) have been postulated as potential strategies to ameliorate obesity, inflammation, and gut microbiota (GM) with promising results. However, the impact of the combination of both Exe and Gen is yet to be investigated. We aimed to analyze the impacts of Exe, Gen, and their combined effects on GM and inflammation in mice after a 12-week high-fat, high-sugar diet (HFD). Eighty-three C57BL/6 mice were randomized to control, HFD, HFD + Exe, HFD + Gen, or HFD + Exe + Gen. The V4 region of the 16S rRNA gene was analyzed with Illumina MiSeq. Serum samples were used to analyze interleukin (Il)-6 and Tumor Necrosis Factor alpha (TNF-alpha). The HFD + Exe and HFD + Exe + Gen treatments resulted in significantly greater microbial richness compared to HFD. All the treatments had a significantly different impact on the GM community structure. Ruminococcus was significantly more abundant after the HFD + Exe + Gen treatment when compared to all the other HFD groups. Exe + Gen resulted in serum Il-6 concentrations similar to that of controls. TNF-alpha concentrations did not differ by treatment. Overall, Exe had a positive impact on microbial richness, and Ruminococcus might be the driving bacteria for the GM structure differences. Exe + Gen may be an effective treatment for preventing HFD-induced inflammation.
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Li H, Li J, Qu Z, Qian H, Zhang J, Wang H, Xu X, Liu S. Intrauterine exposure to low-dose DBP in the mice induces obesity in offspring via suppression of UCP1 mediated ER stress. Sci Rep 2020; 10:16360. [PMID: 33004990 PMCID: PMC7529907 DOI: 10.1038/s41598-020-73477-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Accepted: 09/17/2020] [Indexed: 12/17/2022] Open
Abstract
Dibutyl phthalate (DBP) is recognized as an environmental endocrine disruptor that has been detected in fetal and postnatal samples. Recent evidence found that in utero DBP exposure was associated with an increase of adipose tissue weight and serum lipids in offspring, but the precise mechanism is unknown. Here we aimed to study the effects of in utero DBP exposure on obesity in offspring and examine possible mechanisms. SPF C57BL/6J pregnant mice were gavaged with either DBP (5 mg /kg/day) or corn oil, from gestational day 12 until postnatal day 7. After the offspring were weaned, the mice were fed a standard diet for 21 weeks, and in the last 2 weeks 20 mice were selected for TUDCA treatment. Intrauterine exposure to low-dose DBP promoted obesity in offspring, with evidence of glucose and lipid metabolic disorders and a decreased metabolic rate. Compared to controls, the DBP exposed mice had lower expression of UCP1 and significantly higher expression of Bip and Chop, known markers of endoplasmic reticulum (ER) stress. However, TUDCA treatment of DBP exposed mice returned these parameters nearly to the levels of the controls, with increased expression of UCP1, lower expression of Bip and Chop and ameliorated obesity. Intrauterine exposure of mice to low-dose DBP appears to promote obesity in offspring by inhibiting UCP1 via ER stress, a process that was largely reversed by treatment with TUDCA.
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Affiliation(s)
- Huan Li
- School of Public Health, Beihua University, Jilin, 132013, China
| | - Jianqiao Li
- School of Public Health, Beihua University, Jilin, 132013, China
| | - Zhenting Qu
- Jilin Combine Traditional Chinese and Western Hospital, Jilin, 132012, China
| | - Honghao Qian
- School of Public Health, Beihua University, Jilin, 132013, China
| | - Jing Zhang
- School of Public Health, Beihua University, Jilin, 132013, China
| | - Hongyan Wang
- School of Public Health, Beihua University, Jilin, 132013, China
| | - Xiaolei Xu
- School of Public Health, Beihua University, Jilin, 132013, China
| | - Shengyuan Liu
- Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, 518054, China.
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Zhao Y, Zhu Y, Wang P, Sang S. Dietary Genistein Reduces Methylglyoxal and Advanced Glycation End Product Accumulation in Obese Mice Treated with High-Fat Diet. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:7416-7424. [PMID: 32573222 DOI: 10.1021/acs.jafc.0c03286] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Our previous study has found that dietary genistein could ameliorate high-fat diet (HFD)-induced obesity and especially lower methylglyoxal (MGO) and advanced glycation end product (AGE) accumulation in healthy mice exposed to genistein and HFD. However, it is still unclear whether dietary genistein intervention has a similar beneficial effect in obese mice. In this study, the mice were induced with obesity after being fed a HFD for nine weeks before being administered with two doses of genistein, 0.1% (G 0.1) and 0.2% (G 0.2), in the HFD for additional 19 weeks. After 19 week treatment, genistein supplementation reduced body and liver weights, plasma and liver MGO levels, and kidney AGE levels in mice. Mechanistically, genistein upregulated the expressions of glyoxalase I and II and aldose reductase to detoxify MGO, and genistein and its microbial metabolites, dihydrogenistein and 6'-hydroxy-O-demethylangolensin, were able to trap endogenous MGO via formation of MGO conjugates. Taken together, our results provide novel insights into the antiobesity and antiglycation roles of dietary genistein in obese subjects.
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Affiliation(s)
- Yantao Zhao
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, North Carolina 28081, United States
| | - Yingdong Zhu
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, North Carolina 28081, United States
| | - Pei Wang
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, North Carolina 28081, United States
| | - Shengmin Sang
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, North Carolina 28081, United States
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Genistein and exercise modulated lipid peroxidation and improved steatohepatitis in ovariectomized rats. BMC Complement Med Ther 2020; 20:162. [PMID: 32482167 PMCID: PMC7262771 DOI: 10.1186/s12906-020-02962-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 05/19/2020] [Indexed: 12/17/2022] Open
Abstract
Background The prevalence of nonalcoholic steatohepatitis (NASH) in menopausal women is increasing, but current treatments have not been proven effective. The objective of this study was to investigate the treatment effects of genistein and running exercise in ovariectomized (OVX) rats with NASH. Methods Thirty-six female Sprague-Dawley rats were divided into 6 groups, control; OVX with standard diet; OVX with high fat and high fructose (HFHF) diet for 4 weeks; OVX with HFHF and genistein treatment (16 mg/kg BW/day) for 5 weeks (OVX + HFHF+GEN); OVX with HFHF and moderate intensity exercise for 5 weeks (OVX + HFHF+EX); OVX with HFHF and combined treatments (OVX + HFHF+GEN + EX). Serum interleukin-6 (IL-6) levels, hepatic free fatty acid (FFA), hepatic glutathione (GSH), and hepatic malondialdehyde (MDA) levels were measured. Liver histology was examined to determine NASH severity. Results OVX + HFHF group had the highest levels of hepatic FFA compared with OVX and control groups (5.92 ± 0.84 vs. 0.37 ± 0.01 vs. 0.42 ± 0.04 nmol/mg protein, respectively, p < 0.01). Serum IL-6 levels were significantly elevated in both OVX and OVX + HFHF groups as compared with controls (112.13 ± 6.50 vs. 121.47 ± 3.96 vs. 86.13 ± 2.40 pg/mL, respectively, p < 0.01). In OVX + HFHF group, hepatic MDA levels were higher, while GSH levels were lower than in OVX and control groups (MDA; 0.98 ± 0.04 vs. 0.82 ± 0.02 vs. 0.78 ± 0.03 nmol/mg protein, and GSH; 46.01 ± 0.91 vs. 55.21 ± 1.40 vs. 57.94 ± 0.32, respectively; p < 0.01 for both). Comparing with OVX + HFHF group, rats that received genistein, exercise and combined treatments demonstrated an improvement in liver histopathology, decreased levels of hepatic FFA (1.44 ± 0.21 vs. 0.45 ± 0.04 vs. 0.49 ± 0.05 nmol/mg protein, respectively, p < 0.01), serum IL-6 (82.80 ± 2.07 vs. 83.47 ± 2.81 vs. 94.13 ± 1.61 pg/mL, respectively, p < 0.01), and hepatic MDA (0.80 ± 0.03 vs. 0.76 ± 0.02 vs. 0.76 ± 0.03 nmol/mg protein, respectively, p < 0.01). Conclusions Genistein and moderate intensity exercise were effective in reducing the severity of NASH in OVX rats through the reduction in liver inflammation, oxidative stress and liver fat contents.
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Endocrine disruption and obesity: A current review on environmental obesogens. CURRENT RESEARCH IN GREEN AND SUSTAINABLE CHEMISTRY 2020; 3. [PMCID: PMC7326440 DOI: 10.1016/j.crgsc.2020.06.002] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/17/2023]
Abstract
Obesity represents an important public health concern because it substantially increases the risk of multiple chronic diseases and thereby contributing to a decline in both quality of life and life expectancy. Besides unhealthy diet, physical inactivity and genetic susceptibility, environmental pollutants also contribute to the rising prevalence of obesity epidemic. An environmental obesogen is defined as a chemical that can alter lipid homeostasis to promote adipogenesis and lipid accumulation whereas an endocrine disrupting chemical (EDC) is defined as a synthetic chemical that can interfere with the endocrine function and cause adverse health effects. Many obesogens are EDCs that interfere with normal endocrine regulation of metabolism, adipose tissue development and maintenance, appetite, weight and energy balance. An expanding body of scientific evidence from animal and epidemiological studies has begun to provide links between exposure to EDCs and obesity. Despite the significance of environmental obesogens in the pathogenesis of metabolic diseases, the contribution of synthetic chemical exposure to obesity epidemic remains largely unrecognised. Hence, the purpose of this review is to provide a current update on the evidences from animal and human studies on the role of fourteen environmental obesogens in obesity, a comprehensive view of the mechanisms of action of these obesogens and current green and sustainable chemistry strategies to overcome chemical exposure to prevent obesity. Designing of safer version of obesogens through green chemistry approaches requires a collaborative undertaking to evaluate the toxicity of endocrine disruptors using appropriate experimental methods, which will help in developing a new generation of inherently safer chemicals.
Many environmental obesogens are endocrine disrupting chemicals that interfere with normal endocrine regulation of metabolism. Understanding the role of environmental obesogens in the epidemics of obesity is in an infant stage. Green chemistry approach aims to design a safer version of these chemicals by understanding their hazardous effects. Further studies are necessary to fully establish the hazardous effects of obesogens and their association to human obesity.
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Wang J, Zhang X, Zhang L, Yan T, Wu B, Xu F, Jia Y. Silychristin A activates Nrf2-HO-1/SOD2 pathway to reduce apoptosis and improve GLP-1 production through upregulation of estrogen receptor α in GLUTag cells. Eur J Pharmacol 2020; 881:173236. [PMID: 32497626 DOI: 10.1016/j.ejphar.2020.173236] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 05/21/2020] [Accepted: 05/29/2020] [Indexed: 01/08/2023]
Abstract
Glucagon-like peptide-1 (GLP-1), a glucagon-like peptide secreted mainly from intestinal L cells, possesses the functions of promoting synthesis and secretion of insulin in pancreatic β-cells, and maintaining glucose homeostasis in an insulin-independent manner. Silychristin A, a major flavonolignan from silymarin, was reported to protect pancreatic β-cells from oxidative damage in streptozotocin (STZ)-induced diabetic rats. However, the role of silychristin A in the protection of intestinal L-cells is still unknown. Our current study demonstrated that palmitate (PA) inhibited protein expression of NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and superoxide dismutase 2 (SOD2), and subsequently increased reactive oxygen species level to induce apoptosis and decrease GLP-1 content in intestinal L-cell line GLUTag cells. Pre-incubation of silychristin A effectively reversed PA-inactivated Nrf2-HO-1/SOD2 antioxidative pathway accompanied with decreased apoptosis level and increased GLP-1 level in GLUTag cells. As a potential target of silychristin A, estrogen receptor α was shown to be downregulated by PA stimulation, and the expression of which was improved by silychristin A in a concentration-dependent manner. Further study revealed that the treatment of estrogen receptor α antagonist MPP induced apoptosis and blocked the stimulation of GLP-1 production by silychristin A through the activation of Nrf2-HO-1/SOD2 pathway in GLUTag cells. Taken together, our study found silychristin A activated estrogen receptor α-dependent Nrf2-HO-1/SOD2 pathway to decrease apoptosis and upregulate GLP-1 production in GLUTag cells.
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Affiliation(s)
- Jinyu Wang
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, PR China
| | - Xiaoying Zhang
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, PR China
| | - Luxin Zhang
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, PR China
| | - Tingxu Yan
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, PR China
| | - Bo Wu
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, PR China
| | - Fanxing Xu
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, PR China.
| | - Ying Jia
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, PR China.
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Griffin MD, Pereira SR, DeBari MK, Abbott RD. Mechanisms of action, chemical characteristics, and model systems of obesogens. BMC Biomed Eng 2020; 2:6. [PMID: 32903358 PMCID: PMC7422567 DOI: 10.1186/s42490-020-00040-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Accepted: 04/07/2020] [Indexed: 02/06/2023] Open
Abstract
There is increasing evidence for the role of environmental endocrine disrupting contaminants, coined obesogens, in exacerbating the rising obesity epidemic. Obesogens can be found in everyday items ranging from pesticides to food packaging. Although research shows that obesogens can have effects on adipocyte size, phenotype, metabolic activity, and hormone levels, much remains unknown about these chemicals. This review will discuss what is currently known about the mechanisms of obesogens, including expression of the PPARs, hormone interference, and inflammation. Strategies for identifying obesogenic chemicals and their mechanisms through chemical characteristics and model systems will also be discussed. Ultimately, research should focus on improving models to discern precise mechanisms of obesogenic action and to test therapeutics targeting these mechanisms.
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Affiliation(s)
- Mallory D. Griffin
- Carnegie Mellon University, 5000 Forbes Avenue, Scott Hall, Pittsburgh, PA 15213 USA
| | - Sean R. Pereira
- Carnegie Mellon University, 5000 Forbes Avenue, Scott Hall, Pittsburgh, PA 15213 USA
| | - Megan K. DeBari
- Carnegie Mellon University, 5000 Forbes Avenue, Scott Hall, Pittsburgh, PA 15213 USA
| | - Rosalyn D. Abbott
- Carnegie Mellon University, 5000 Forbes Avenue, Scott Hall, Pittsburgh, PA 15213 USA
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Feeding brown fat: dietary phytochemicals targeting non-shivering thermogenesis to control body weight. Proc Nutr Soc 2020; 79:338-356. [PMID: 32290888 PMCID: PMC7663322 DOI: 10.1017/s0029665120006928] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Excessive adipose accumulation, which is the main driver for the development of secondary metabolic complications, has reached epidemic proportions and combined pharmaceutical, educational and nutritional approaches are required to reverse the current rise in global obesity prevalence rates. Brown adipose tissue (BAT) is a unique organ able to dissipate energy and thus a promising target to enhance BMR to counteract a positive energy balance. In addition, active BAT might support body weight maintenance after weight loss to prevent/reduce relapse. Natural products deliver valuable bioactive compounds that have historically helped to alleviate disease symptoms. Interest in recent years has focused on identifying nutritional constituents that are able to induce BAT activity and thereby enhance energy expenditure. This review provides a summary of selected dietary phytochemicals, including isoflavones, catechins, stilbenes, the flavonoids quercetin, luteolin and resveratrol as well as the alkaloids berberine and capsaicin. Most of the discussed phytochemicals act through distinct molecular pathways e.g. sympathetic nerve activation, AMP-kinase signalling, SIRT1 activity or stimulation of oestrogen receptors. Thus, it might be possible to utilise this multitude of pathways to co-activate BAT using a fine-tuned combination of foods or combined nutritional supplements.
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Kuryłowicz A, Cąkała-Jakimowicz M, Puzianowska-Kuźnicka M. Targeting Abdominal Obesity and Its Complications with Dietary Phytoestrogens. Nutrients 2020; 12:nu12020582. [PMID: 32102233 PMCID: PMC7071386 DOI: 10.3390/nu12020582] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 02/19/2020] [Accepted: 02/20/2020] [Indexed: 12/21/2022] Open
Abstract
In the assessment of the health risk of an obese individual, both the amount of adipose tissue and its distribution and metabolic activity are essential. In adults, the distribution of adipose tissue differs in a gender-dependent manner and is regulated by sex steroids, especially estrogens. Estrogens affect adipocyte differentiation but are also involved in the regulation of the lipid metabolism, insulin resistance, and inflammatory activity of the adipose tissue. Their deficiency results in unfavorable changes in body composition and increases the risk of metabolic complications, which can be partially reversed by hormone replacement therapy. Therefore, the idea of the supplementation of estrogen-like compounds to counteract obesity and related complications is compelling. Phytoestrogens are natural plant-derived dietary compounds that resemble human estrogens in their chemical structure and biological activity. Supplementation with phytoestrogens may confer a range of beneficial effects. However, results of studies on the influence of phytoestrogens on body composition and prevalence of obesity are inconsistent. In this review, we present data from in vitro, animal, and human studies regarding the role of phytoestrogens in adipose tissue development and function in the context of their potential application in the prevention of visceral obesity and related complications.
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Affiliation(s)
- Alina Kuryłowicz
- Department of Human Epigenetics, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego Street, 02-106 Warsaw, Poland; (M.C.-J.); (M.P.-K.)
- Correspondence: ; Tel.: +48226086591; Fax: +48226086410
| | - Marta Cąkała-Jakimowicz
- Department of Human Epigenetics, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego Street, 02-106 Warsaw, Poland; (M.C.-J.); (M.P.-K.)
| | - Monika Puzianowska-Kuźnicka
- Department of Human Epigenetics, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego Street, 02-106 Warsaw, Poland; (M.C.-J.); (M.P.-K.)
- Department of Geriatrics and Gerontology, Medical Centre of Postgraduate Education, 61/63 Kleczewska Street, 01-826, Warsaw, Poland
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Smeriglio A, Calderaro A, Denaro M, Laganà G, Bellocco E. Effects of Isolated Isoflavones Intake on Health. Curr Med Chem 2019; 26:5094-5107. [PMID: 28990503 DOI: 10.2174/0929867324666171006143047] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Revised: 09/16/2017] [Accepted: 09/21/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND Isoflavones are naturally occurring flavonoids, commonly found in the food consumed for centuries in the East-Asian population, characterized by a structure able to exert nonsteroidal estrogen-like activity on human cells. They have attracted researcher interest all around the word, following the results obtained in epidemiological and clinical studies. The involvement of isoflavones and their metabolites in various biological processes suggests that they can influence several metabolic pathways and can influence the gene expression at epigenetic level, involving effects that probably are due to early life exposure. They show positive health effects on several diseases, especially in the prevention of coronary heart and neurological diseases, hormone-related cancers, osteoporosis, and postmenopausal symptoms. METHODS We have performed a critical evaluation of available literature trough a structured search of bibliographic databases about isoflavones health promoting properties, risk assessment and mechanisms of action. In addition, we supplied useful information on their biochemical properties, sources and bioavailability. RESULTS Although these molecules have been the subjects of numerous researches, their role for the wellness of the human organism remains controversial. Moreover, there are substantial inconsistencies between the results obtained by epidemiologic studies conducted on Eastern population, which found high health promoting properties, and Western clinical trials, which found much less positive effects. CONCLUSION Further epidemiologic studies and well-designed prospective human studies are to determine the beneficial effects of isoflavones exposure, as well as establishing its safe therapeutic.
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Affiliation(s)
- Antonella Smeriglio
- Department of Chemical, University of Messina, Biological, Pharmaceutical and Environmental Sciences, Viale F. Stagno d'Alcontres 31, Messina, Italy
| | - Antonella Calderaro
- Department of Chemical, University of Messina, Biological, Pharmaceutical and Environmental Sciences, Viale F. Stagno d'Alcontres 31, Messina, Italy
| | - Marcella Denaro
- Department of Chemical, University of Messina, Biological, Pharmaceutical and Environmental Sciences, Viale F. Stagno d'Alcontres 31, Messina, Italy
| | - Giuseppina Laganà
- Department of Chemical, University of Messina, Biological, Pharmaceutical and Environmental Sciences, Viale F. Stagno d'Alcontres 31, Messina, Italy
| | - Ersilia Bellocco
- Department of Chemical, University of Messina, Biological, Pharmaceutical and Environmental Sciences, Viale F. Stagno d'Alcontres 31, Messina, Italy
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Yoon H, Yoon YS, Kim SG, Oh HJ, Choi CW, Seong JM, Park J. Relationship between metabolic syndrome and metabolic syndrome score with β-cell function by gender in non-diabetic Korean populations. Endocr Res 2019; 44:71-80. [PMID: 30339044 DOI: 10.1080/07435800.2018.1524476] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Aims: The present study was conducted to assess the association of metabolic syndrome (MetS) and the MetS score (MSS) with β-cell function by gender in Korean non-diabetic populations. Methods: This study used the data from the 2015 Korean National Health and Nutrition Examination Survey including 4380 adults, aged 20 or older. Results: After adjusting for related variables (with exception of body mass index [BMI]), MetS (p < 0.001) and MSS (p < 0.001) were positively associated with homeostasis model assessment of β-cell function (HOMA-B), in both men and women. When further adjusting for BMI, MetS (p = 0.002) and MSS (p = 0.006) were positively associated with HOMA-B in women, whereas the association of MetS (p = 0.140) or MSS (p = 0.697) and HOMA-B was no longer significant in men. Conclusion: MetS and MSS increases were positively associated with β-cell function in non-diabetic Korean women, but not in non-diabetic Korean men.
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Affiliation(s)
- Hyun Yoon
- a Department of Biomedical Laboratory Science , Hanlyo University , Gwangyangsi , Jeollanamdo , South Korea
| | - Yo Sang Yoon
- b Department of Radiological Science , Hanlyo University , Gwangyangsi , Jeollanamdo , South Korea
| | - Sung Gil Kim
- b Department of Radiological Science , Hanlyo University , Gwangyangsi , Jeollanamdo , South Korea
| | - Hye Jong Oh
- a Department of Biomedical Laboratory Science , Hanlyo University , Gwangyangsi , Jeollanamdo , South Korea
| | - Cheol Won Choi
- a Department of Biomedical Laboratory Science , Hanlyo University , Gwangyangsi , Jeollanamdo , South Korea
| | - Jeong Min Seong
- c Department of Dental Hygiene , College of Health Science, Kangwon National University , Samcheok-si , Gangwon-do , South Korea
| | - Jong Park
- d Department of Preventive Medicine , Chosun University Medical School , Gwangju , South Korea
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Usategui‐Martín R, Pérez‐Alonso M, Socorro‐Briongos L, Ruiz‐Mambrilla M, Luis D, Linares L, Calero‐Paniagua I, Dueñas‐Laita A, Pérez‐Castrillón JL. Estrogen receptor genes polymorphisms determine serum lipid profile in healthy postmenopausal women treated with calcium, vitamin D, and genistein. J Cell Biochem 2019; 120:13115-13120. [DOI: 10.1002/jcb.28584] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Revised: 12/21/2018] [Accepted: 01/07/2019] [Indexed: 11/12/2022]
Affiliation(s)
- Ricardo Usategui‐Martín
- Instituto Universitario de Oftalmobiología Aplicada (IOBA), University of Valladolid Valladolid Spain
| | | | - Laisa Socorro‐Briongos
- Department of Internal Medicine, Río Hortega University Hospital, Departament of Medicine University of Valladolid Valladolid Spain
| | - Marta Ruiz‐Mambrilla
- Department of Medicine University of Valladolid Valladolid Spain
- Rehabilitation and Language Medical Centre Valladolid Spain
| | - Daniel Luis
- Department of Endocrinology Valladolid University Hospital. University of Valladolid Valladolid Spain
| | - Lidia Linares
- Department of Endocrinology Valladolid University Hospital. University of Valladolid Valladolid Spain
| | | | - Antonio Dueñas‐Laita
- Service of Clinical Toxicology, Río Hortega University Hospital, Departament of Medicine University of Valladolid Valladolid Spain
| | - José L. Pérez‐Castrillón
- Department of Internal Medicine, Río Hortega University Hospital, Departament of Medicine University of Valladolid Valladolid Spain
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Hall JM, Powell HR, Rajic L, Korach KS. The Role of Dietary Phytoestrogens and the Nuclear Receptor PPARγ in Adipogenesis: An in Vitro Study. ENVIRONMENTAL HEALTH PERSPECTIVES 2019; 127:37007. [PMID: 30920877 PMCID: PMC6768326 DOI: 10.1289/ehp3444] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 02/04/2019] [Accepted: 02/08/2019] [Indexed: 05/26/2023]
Abstract
BACKGROUND Phytoestrogens, naturally occurring plant chemicals, have long been thought to confer beneficial effects on human cardiovascular and metabolic health. However, recent epidemiological studies, have yielded conflicting outcomes, in which phytoestrogen consumption was both positively and negatively correlated with adiposity. Interestingly, several dietary phytoestrogens are known to stimulate or inhibit the activity of the peroxisome proliferator-activated receptor gamma (PPARγ), a key physiological regulator of adipogenesis. OBJECTIVE The objective of this study was to test the hypothesis that the pro- or anti-adipogenic activity of phytoestrogen chemicals is related to the ability to activate PPARγ in adipocytes. METHODS The effects of resveratrol and the soy isoflavones genistein and daidzein on adipogenesis were examined in cell-based assays using the 3T3-L1 cell model. In parallel, ligand-mediated alterations in PPARγ target gene expression were measured by quantitative polymerase chain reaction. The agonist/antagonist activities of phytoestrogens on PPARγ were further assessed by quantifying their ability to affect recruitment of transcriptional cofactors to the receptor. RESULTS Resveratrol displayed significant anti-adipogenic activities as exhibited by the ability to antagonize PPARγ-dependent adipocyte differentiation, down-regulate genes involved in lipid metabolism, block cofactor recruitment to PPARγ, and antagonize the effects of the PPARγ agonist rosiglitazone. In contrast, genistein and daidzein functioned as PPARγ agonists while also displaying pro-adipogenic activities. CONCLUSIONS These data provide biological evidence that the pro- or anti-obesity effects of phytoestrogens are related to their relative agonist/antagonist activity on PPARγ. Thus, PPARγ-activation assays may enable the screening of dietary components and identification of agents with adipogenic activities. https://doi.org/10.1289/EHP3444.
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Affiliation(s)
- Julie M. Hall
- Department of Medical Sciences, Frank H. Netter MD School of Medicine NH-MED, Quinnipiac University, North Haven, Connecticut, USA
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Campbell University, Buies Creek, North Carolina, USA
| | - Heather R. Powell
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Campbell University, Buies Creek, North Carolina, USA
| | - Lara Rajic
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Campbell University, Buies Creek, North Carolina, USA
| | - Kenneth S. Korach
- Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA
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Lee KH, Kim NH. Expressional Patterns of Adipocyte-Associated Molecules in the Rat Epididymal Fat during Postnatal Development Period. Dev Reprod 2019; 22:351-360. [PMID: 30680334 PMCID: PMC6344364 DOI: 10.12717/dr.2018.22.4.351] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2018] [Revised: 11/06/2018] [Accepted: 11/29/2018] [Indexed: 12/11/2022]
Abstract
The adipogenesis is a maturation process of pre-adipocyte cell into mature
lipid-filled adipocyte cell. The adipogenesis begins at the late prenatal stage
and continues until the early postnatal age. Because the adipogenesis and
formation of adipose tissue persist during postnatal period and are precisely
regulated by the action of numerous gene products, the present research was
attempted to determine the expressional patterns of adipose tissue-associated
genes in the rat epididymal fat pad at different postnatal ages, from 7 days to
2 years of ages, using a quantitative real-time PCR analysis. The basal
expression levels of CCAAT/enhancer binding protein gamma, sterol regulatory
element binding transcription factor 1, fatty acid binding protein 4,
adiponectin, leptin, and resistin at the early postnatal ages were significantly
lower than those at the elderly ages, even though a fluctuation of expressional
levels was observed at some ages. The lowest expressional level of delta like
non-canonical Notch ligand 1 was detected at 44 days and 5 months of ages. The
expression of peroxisome proliferator-activated receptor gamma (PPARγ)
was the highest at 44 days of age, followed by a diminished expression of
PPARγ at the elderly ages. These results indicate the existence of a
complex regulatory mechanism (s) for expression of adipose tissue-associated
genes in the rat epididymal fat during postnatal period.
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Affiliation(s)
- Ki-Ho Lee
- Dept. of Biochemistry and Molecular Biology, College of Medicine, Eulji University, Daejeon 34824, Korea
| | - Nan Hee Kim
- Dept. of Biochemistry and Molecular Biology, College of Medicine, Eulji University, Daejeon 34824, Korea
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Ronis MJ, Gomez-Acevedo H, Shankar K, Sharma N, Blackburn M, Singhal R, Mercer KE, Badger TM. EB 2017 Article: Soy protein isolate feeding does not result in reproductive toxicity in the pre-pubertal rat testis. Exp Biol Med (Maywood) 2019; 243:695-707. [PMID: 29763383 DOI: 10.1177/1535370218771333] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
The isoflavone phytoestrogens found in the soy protein isolate used in soy infant formulas have been shown to have estrogenic actions in the developing male reproductive tract resulting in reproductive toxicity. However, few studies have examined potential estrogenicity of soy protein isolate as opposed to that of pure isoflavones. In this study, we fed weanling male Sprague-Dawley rats a semi-purified diet with casein or soy protein isolate as the sole protein source from postnatal day 21 to 33. Additional groups were fed casein or soy protein isolate and treated s.c. with 10 µg/kg/d estradiol via osmotic minipump. Estradiol treatment reduced testis, prostate weights, and serum androgen concentrations ( P < 0.05). Soy protein isolate had no effect. Estradiol up-regulated 489 and down-regulated 1237 testicular genes >1.5-fold ( P < 0.05). In contrast, soy protein isolate only significantly up-regulated expression of 162 genes and down-regulated 16 genes. The top 30 soy protein isolate-up-regulated genes shared 93% concordance with estradiol up-regulated genes. There was little overlap between soy protein isolate down-regulated genes and those down-regulated by estradiol treatment. Functional annotation analysis revealed significant differences in testicular biological processes affected by estradiol or soy protein isolate. Estradiol had major actions on genes involved in reproductive processes including down-regulation of testicular steroid synthesis and expression of steroid receptor activated receptor (Star) and cytochrome P450 17α-hydroxylase/(Cyp17a1). In contrast, soy protein isolate primarily affected pathways associated with macromolecule modifications including ubiquitination and histone methylation. Our results indicate that rather than acting as a weak estrogen in the developing testis, soy protein isolate appears to act as a selective estrogen receptor modulator with little effect on reproductive processes. Impact statement Soy protein isolate (SPI) is the sole protein used to make soy-based infant formulas. SPI contains phytoestrogens, which are structurally similar to estradiol. These phytoestrogens, daidzein, genistein, and equol, fit the definition of endocrine-disrupting compounds, and at high concentrations, have estrogenic actions resulting in reproductive toxicity in the developing male, when provided as isolated chemicals. However, few animal studies have examined the potential estrogenicity of SPI as opposed to pure isoflavones. In this study, SPI feeding did not elicit an estrogenic response in the testis nor any adverse outcomes including reduced testicular growth, or androgen production during early development in rats when compared to those receiving estradiol. These findings are consistent with emerging data showing no differences in reproductive development in males and female children that received breast milk, cow's milk formula, or soy infant formula during the postnatal feeding period.
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Affiliation(s)
- Martin Jj Ronis
- 1 Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center - New Orleans, LA 70112, USA
| | - Horacio Gomez-Acevedo
- 2 Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Kartik Shankar
- 3 Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.,4 Arkansas Children's Nutrition Center, Little Rock, AR, 72202, USA
| | - Neha Sharma
- 4 Arkansas Children's Nutrition Center, Little Rock, AR, 72202, USA
| | | | - Rohit Singhal
- 4 Arkansas Children's Nutrition Center, Little Rock, AR, 72202, USA
| | - Kelly E Mercer
- 3 Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.,4 Arkansas Children's Nutrition Center, Little Rock, AR, 72202, USA
| | - Thomas M Badger
- 3 Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.,4 Arkansas Children's Nutrition Center, Little Rock, AR, 72202, USA
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Rockwood S, Mason D, Lord R, Lamar P, Prozialeck W, Al-Nakkash L. Genistein diet improves body weight, serum glucose and triglyceride levels in both male and female ob/ob mice. Diabetes Metab Syndr Obes 2019; 12:2011-2021. [PMID: 31686880 PMCID: PMC6783398 DOI: 10.2147/dmso.s216312] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2019] [Accepted: 08/30/2019] [Indexed: 12/15/2022] Open
Abstract
PURPOSE Diabetic obesity in the leptin-deficient ob/ob mouse is associated with weight gain, and hyperglycemia, along with hyperinsulinemia. We have previously examined the effects of genistein (a naturally occurring isoflavone found in soy) on metabolic disturbances in the ob/ob mouse and demonstrated beneficial effects of genistein (600 mg genistein/kg diet, for 4-weeks) on T3 production and corticosterone status. The goal of this study was to examine whether dietary genistein could prevent, or at least lessen, the typical phenotype in this murine model of diabetic-obesity, and to assess potential sex-differences. PATIENTS AND METHODS The ob/ob mice (male and female) aged 4-5 weeks were randomly assigned to one of two diets for a period of 4-weeks: standard rodent diet, or genistein-containing diet (600 mg genistein/kg diet). Comparisons were made to a lean control group. RESULTS Genistein diet significantly reduced body weight by 12% in females and 9% in males. Genistein significantly lowered serum glucose levels by 18% in females and 43% in males, yet had no effect on serum insulin. Genistein diet significantly lowered serum triglyceride levels in both ob/ob male and female mice returning them to lean levels. In females only, genistein significantly reduced serum pancreatic polypeptide levels by 56% and increased serum GIP levels 2.3-fold. Genistein had sex-dependent effects on hepatic steatosis: in females, genistein further increased the % fat area and the fat droplet diameter 2.6-fold, along with additionally increasing hepatic TBARS. CONCLUSION The results from this study indicate interesting beneficial effects of genistein diet for both male and female ob/ob mice.
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Affiliation(s)
- Schuyler Rockwood
- Arizona College of Osteopathic Medicine, Midwestern University
, Glendale, AZ, USA
| | - Daniel Mason
- Arizona College of Osteopathic Medicine, Midwestern University
, Glendale, AZ, USA
| | - Ryan Lord
- Arizona College of Osteopathic Medicine, Midwestern University
, Glendale, AZ, USA
| | - Peter Lamar
- Department of Pharmacology, College of Graduate Studies, Midwestern University, Downers Grove, IL, USA
| | - Walter Prozialeck
- Department of Pharmacology, College of Graduate Studies, Midwestern University, Downers Grove, IL, USA
| | - Layla Al-Nakkash
- Department of Physiology, College of Graduate Studies, Midwestern University, Glendale, AZ, USA
- Correspondence: Layla Al-Nakkash Department of Physiology, College of Graduate Studies, Midwestern University, 19555 N. 59th Avenue, Glendale, AZ85308, USATel +1 623 572 3719Fax +1 623 572 3673 Email
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Adeogun AO, Ibor OR, Imiuwa ME, Omogbemi ED, Chukwuka AV, Omiwole RA, Arukwe A. Endocrine disruptor responses in African sharptooth catfish (Clarias gariepinus) exposed to di-(2-ethylhexyl)-phthalate. Comp Biochem Physiol C Toxicol Pharmacol 2018; 213:7-18. [PMID: 30033399 DOI: 10.1016/j.cbpc.2018.07.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Revised: 06/08/2018] [Accepted: 07/03/2018] [Indexed: 10/28/2022]
Abstract
In the present study, we have investigated the endocrine disruptive effects of waterborne di-(2-ethylhexyl) phthalate (DEHP: 0 (control), 10, 100, 200 and 400 μg/L) on juvenile Clarias gariepinus by analyzing transcript patterns for hepatic vitellogenin (vtg), estrogen receptor-α (er-α), aromatase (cyp19a1b) and peroxisome proliferator activated receptor-α (ppar-α) using quantitative real-time PCR after 3, 7 and 14 days exposure period. In addition, we analyzed CYP19 and PPAR protein levels using enzyme-linked immunosorbent assay (ELISA), while cellular testosterone (T) and 17β-estradiol (E2) levels were measured using enzyme immune assay (EIA). Tissue burden of DEHP was measured in the liver using gas chromatography-mass spectroscopy (GC-MS). We observed apparent concentration- and time-dependent increases of vtg, er-α, cyp19a1b transcripts, E2 and T levels after exposure to DEHP. A biphasic pattern of effect was observed for ppar-α, showing a concentration-dependent increase that peaked at 100 μg/L and thereafter, an apparent concentration-dependent decrease at 200 and 400 μg/L at all exposure days. Given that the post-differentiation changes of gonads in C. gariepinus corresponded with the 14-day sampling period, we separated the analyzed data into sexes after histological examination of the gonads, showing that females responded stronger, compared to males, to DEHP exposure at all exposure concentrations. Oocyte atresia, intersex (ovotestis) and karyoplasmic clumping were observed in females while male fish showed distortion and degeneration of seminiferous tubules and condensation of tubular cells in the 400 μg/L exposure group after 14 days. Corresponding canonical analysis (CCA) of all analyzed variables revealed a positive relationship between analyzed biological variables with increasing DEHP concentrations. Overall, molecular, biochemical and physiological responses presented in the present study indicate that exposure of C. gariepinus to waterborne DEHP produced endocrine disruptive responses with potential consequences for overt reproduction, development, physiology and general health of fish populations inhabiting phthalate contaminated aquatic environments. These responses represent valuable and effective biomarkers of exposure and effects, that can be adopted for screening the presence of EDCs in Nigeria and other developing countries.
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Affiliation(s)
- Aina O Adeogun
- Department of Zoology, University of Ibadan, Ibadan, Nigeria
| | - Oju R Ibor
- Department of Zoology, University of Ibadan, Ibadan, Nigeria; Department of Zoology and Environmental Biology, University of Calabar, Nigeria
| | | | | | | | | | - Augustine Arukwe
- Department of Biology, Norwegian University of Science and Technology (NTNU), Høgskoleringen 5, N-7491 Trondheim, Norway.
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Lv Z, Xing K, Li G, Liu D, Guo Y. Dietary Genistein Alleviates Lipid Metabolism Disorder and Inflammatory Response in Laying Hens With Fatty Liver Syndrome. Front Physiol 2018; 9:1493. [PMID: 30405443 PMCID: PMC6207982 DOI: 10.3389/fphys.2018.01493] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Accepted: 10/03/2018] [Indexed: 01/21/2023] Open
Abstract
This study investigated the molecular mechanism underlying the effect of dietary genistein (GEN) on fatty liver syndrome (FLS) in laying hens. Hens in the control group (CG) were fed a high-energy and low-choline (HELC) diet to establish the FLS model. The livers of the FLS hens were friable and swollen from hemorrhage. Hepatic steatosis and inflammatory cell infiltration were present around the liver blood vessels. Hens in the low-genistein (LGE) and high-genistein (he) groups were fed GEN at 40 and 400 mg/kg doses, respectively, as supplements to the HELC diet. GEN at 40 mg/kg significantly increased gonadotropin-releasing hormone (GnRH) mRNA expression in the hypothalamus, the serum estrogen (E2) level, and the laying rate, whereas 400 mg/kg of GEN decreased GnRH expression and the laying rate without significantly affecting E2, suggesting that high-dose GEN adversely affected the reproductive performance. Either high- or low-dose GEN treatment could alleviate metabolic disorders and inflammatory responses in FLS hens. GEN significantly decreased the serum ALT, creatinine, triglyceride (TG), total cholesterol (TC), and free fatty acid (FFA) levels. Accordingly, the TG and long-chain fatty acid (LCFA) levels, including long-chain saturated fatty acids (LSFAs) and monounsaturated fatty acids (MUFAs), and the n-6:n-3 polyunsaturated fatty acid (PUFA) ratio in the liver were reduced after the GEN treatments, whereas the levels of C22:0, n-3 family fatty acids, C20:3n6, and C20:4n6 were increased. These results indicated that dietary GEN downregulated the expression of genes related to fatty acid synthesis [sterol regulatory element-binding protein 1 (SREBP1c), liver X receptor alpha (LXRα), fatty acid synthase (FAS), and acetyl coenzyme A synthetase (ACC)] and the fatty acid transporter (FAT). Furthermore, GEN treatments upregulated the transcription of genes related to fatty acid β-oxidation [peroxisome proliferator-activated receptor (PPAR)α, PPARδ, ACOT8, ACAD8, and ACADs] in the liver and reduced PPARγ and AFABP expression in abdominal fat. Dietary GEN alleviated inflammatory cell infiltration in the livers of FLS hens and downregulated TNF-α, IL-6, and IL-1β expression. Moreover, GEN treatment increased SOD activity and decreased malondialdehyde activity in the liver. In conclusion, GEN supplementation in the feed inhibited fatty acid synthesis and enhanced β-oxidation in the liver through the PPAR-ACAD/ACOT and PPAR-LXRα-SREBP1c-ACC/FAS/FAT pathways. Dietary GEN alleviated metabolic disorder and inflammation in the FLS hens by improving the antioxidant capacity and fatty acid profile.
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Affiliation(s)
- Zengpeng Lv
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Kun Xing
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Guang Li
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Dan Liu
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Yuming Guo
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
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Davis JE, Hastings D. Transcriptional Regulation of TCF/LEF and PPARγ by Daidzein and Genistein in 3T3-L1 Preadipocytes. J Med Food 2018; 21:761-768. [DOI: 10.1089/jmf.2017.0136] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Affiliation(s)
- Jeremy E. Davis
- Department of Animal Science, Food and Nutrition, Southern Illinois University, Carbondale, Illinois, USA
| | - Darcie Hastings
- Department of Animal Science, Food and Nutrition, Southern Illinois University, Carbondale, Illinois, USA
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36
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Zheng W, Rogoschin J, Niehoff A, Oden K, Kulling SE, Xie M, Diel P. Combinatory effects of phytoestrogens and exercise on body fat mass and lipid metabolism in ovariectomized female rats. J Steroid Biochem Mol Biol 2018; 178:73-81. [PMID: 29122708 DOI: 10.1016/j.jsbmb.2017.11.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 11/03/2017] [Accepted: 11/05/2017] [Indexed: 12/11/2022]
Abstract
The purpose of this study was to investigate the combinatory effects of an isoflavone (ISO)-rich diet and exercise on fat mass and lipid metabolism in ovariectomized (OVX) rats. Therefore the female Wistar rats were sedentary, performed an intense treadmill uphill running, received ISOs, or a combination of ISOs and running after ovariectomy. The exercise reduced visceral fat mass, adipocyte size and serum leptin in Sham animals and antagonized the increases of these parameters induced by OVX. ISOs reduced OVX induced increase of serum leptin. The combination of training and ISOs was most effective in reducing serum triglyceride levels. In OVX rats the training stimulated the expression of genes associated with fatty acid synthesis (SREBP-1c and FAS) in adipose tissue, soleus muscle, liver and genes associated with fatty acid oxidation (PPARδ and PGC-1α) in adipose tissue. ISOs stimulated the expression of SREBP-1c and FAS in soleus muscle and PGC-1α in adipose tissue, whereas suppressed hepatic SREBP-1c and FAS expression. Strong additive effects of ISOs combined with the training were observed for PPARδ and PGC-1α expressions in soleus muscle. In conclusion our results demonstrate that both the training and ISOs affect fat mass and fatty acid metabolism in OVX rats. The training seems to have a higher impact than ISO exposure in regulating gene expression in adipose tissue. However, the strongest effects for several of the addressed parameters could be observed in the combination group especially in the soleus muscle. Therefore a combination of training and an ISO-rich diet may have beneficial effects on fatty acid metabolism and could be a concept for the prevention of obesity in postmenopausal females.
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Affiliation(s)
- Wenya Zheng
- Institute of Cardiovascular Research and Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sport University Cologne, Germany.
| | - Jana Rogoschin
- Institute of Cardiovascular Research and Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sport University Cologne, Germany
| | - Anja Niehoff
- Institute of Biomechanics and Orthopaedics, German Sport University Cologne, Germany; Cologne Center for Musculoskeletal Biomechanics, Medical Faculty, University of Cologne, Germany
| | - Kristina Oden
- Institute of Cardiovascular Research and Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sport University Cologne, Germany
| | - Sabine E Kulling
- Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Karlsruhe, Germany
| | - Mingyong Xie
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Patrick Diel
- Institute of Cardiovascular Research and Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sport University Cologne, Germany
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Lee KH, Kim NH. Expressional Patterns of Connexin Isoforms in the Rat Epididymal Fat during Postnatal Development. Dev Reprod 2018; 22:29-38. [PMID: 29707682 PMCID: PMC5915765 DOI: 10.12717/dr.2018.22.1.029] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 03/10/2018] [Accepted: 03/17/2018] [Indexed: 12/31/2022]
Abstract
In the multicellular tissue, cell-cell interaction is important for a precise
control of its function. The exchange of signaling molecules between adjacent
cells via connexon allows the functional harmony of cells in the tissue. The
present research was to determine the presence and expressional patterns of
connexin (Cx) isoforms in the rat epididymal fat during
postnatal development using quantitative real-time polymerase chain reaction
(PCR) analysis. Of 13 Cx isoforms examined, expression of 11
Cx isoforms in the epididymal fat during postnatal
development was detected. These Cx isoforms include
Cx26, Cx31, Cx31.1,
Cx32, Cx33, Cx36,
Cx37, Cx40, Cx43,
Cx45, and Cx50. Expressional levels of all
Cx isoforms at 1 and 2 years of age were significantly
higher than those at the early postnatal ages, such as 7 days, 14 days, and 24
days of ages. Except Cx33 and Cx43, the
transcript levels of rest Cx isoforms at 1 year of age were
significantly lower than that at 2 years of age. In addition, expressional
patterns of Cx isoforms between 7 days and 5 months of ages
generally varied according to the isoform. The existence of various
Cx isoforms in the rat epididymal fat has been identified
and expression of each Cx isoform in the epididymal fat during
postnatal development has shown a particular pattern, distinguishable from the
others. To our knowledges, this is the first report showing expressional
patterns of Cx isoforms at transcript level in the epididymal
fat at various postnatal ages.
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Affiliation(s)
- Ki-Ho Lee
- Dept. of Biochemistry and Molecular Biology, College of Medicine, Eulji University, Daejeon 34824, Korea
| | - Nan Hee Kim
- Dept. of Biochemistry and Molecular Biology, College of Medicine, Eulji University, Daejeon 34824, Korea
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Marraudino M, Bonaldo B, Farinetti A, Panzica G, Ponti G, Gotti S. Metabolism Disrupting Chemicals and Alteration of Neuroendocrine Circuits Controlling Food Intake and Energy Metabolism. Front Endocrinol (Lausanne) 2018; 9:766. [PMID: 30687229 PMCID: PMC6333703 DOI: 10.3389/fendo.2018.00766] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2018] [Accepted: 12/06/2018] [Indexed: 12/18/2022] Open
Abstract
The metabolism-disrupting chemicals (MDCs) are molecules (largely belonging to the category of endocrine disrupting chemicals, EDCs) that can cause important diseases as the metabolic syndrome, obesity, Type 2 Diabetes Mellitus or fatty liver. MDCs act on fat tissue and liver, may regulate gut functions (influencing absorption), but they may also alter the hypothalamic peptidergic circuits that control food intake and energy metabolism. These circuits are normally regulated by several factors, including estrogens, therefore those EDCs that are able to bind estrogen receptors may promote metabolic changes through their action on the same hypothalamic circuits. Here, we discuss data showing how the exposure to some MDCs can alter the expression of neuropeptides within the hypothalamic circuits involved in food intake and energy metabolism. In particular, in this review we have described the effects at hypothalamic level of three known EDCs: Genistein, an isoflavone (phytoestrogen) abundant in soy-based food (a possible new not-synthetic MDC), Bisphenol A (compound involved in the manufacturing of many consumer plastic products), and Tributyltin chloride (one of the most dangerous and toxic endocrine disruptor, used in antifouling paint for boats).
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Affiliation(s)
- Marilena Marraudino
- Neuroscience Institute Cavalieri Ottolenghi, Turin, Italy
- Department of Neuroscience “Rita Levi-Montalcini”, University of Turin, Turin, Italy
| | - Brigitta Bonaldo
- Neuroscience Institute Cavalieri Ottolenghi, Turin, Italy
- Department of Neuroscience “Rita Levi-Montalcini”, University of Turin, Turin, Italy
| | - Alice Farinetti
- Neuroscience Institute Cavalieri Ottolenghi, Turin, Italy
- Department of Neuroscience “Rita Levi-Montalcini”, University of Turin, Turin, Italy
| | - GianCarlo Panzica
- Neuroscience Institute Cavalieri Ottolenghi, Turin, Italy
- Department of Neuroscience “Rita Levi-Montalcini”, University of Turin, Turin, Italy
- *Correspondence: GianCarlo Panzica
| | - Giovanna Ponti
- Neuroscience Institute Cavalieri Ottolenghi, Turin, Italy
- Department of Veterinary Sciences, University of Turin, Turin, Italy
| | - Stefano Gotti
- Neuroscience Institute Cavalieri Ottolenghi, Turin, Italy
- Department of Neuroscience “Rita Levi-Montalcini”, University of Turin, Turin, Italy
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39
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Milošević N, Milić N, Živanović Bosić D, Bajkin I, Perčić I, Abenavoli L, Medić Stojanoska M. Potential influence of the phthalates on normal liver function and cardiometabolic risk in males. ENVIRONMENTAL MONITORING AND ASSESSMENT 2017; 190:17. [PMID: 29234897 DOI: 10.1007/s10661-017-6398-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2017] [Accepted: 12/05/2017] [Indexed: 05/05/2023]
Abstract
Phthalates are ubiquitous environmental contaminants, massively used in industry as plasticizers and additives in cosmetics, which may impair the human endocrine system inducing fertility problems, respiratory diseases, obesity, and neuropsychological disorders. The aim of this study was to examine the influence of the monoethyl phthalate (MEP) and mono-(2-ethylhexyl) phthalate (MEHP) on the liver function and cardiometabolic risk factors in males. In this research, 102 male participants (51 normal weight and 51 overweight/obese) were enrolled and examined for phthalate metabolites exposure in urine samples after 12 h of fasting. MEP was found in 28.43% (29/102) volunteers, while MEHP was detected among 20.59% (21/102) participants. Statistically significant increment in transaminase serum levels was observed in MEP-positive normal weight subgroup. Linear correlation was obtained between MEP concentration in urine samples and triglyceride (TG) serum levels (r 2 = 0.33; p < 0.01), visceral adiposity index (VAI) (r 2 = 0.41; p < 0.01), lipid accumulation product (LAP) (r 2 = 0.32; p < 0.01), and TG to high-density lipoprotein (HDL) ratio (r 2 = 0.40, p < 0.01) among the obese. The MEHP-positive normal weight volunteers had statistically significant increment of body mass index (p = 0.03) compared to MEHP-negative participants. Urine MEHP concentrations were negatively correlated with HDL serum levels (r 2 = 0.31; p < 0.05) in the normal weight subgroup. The phthalates exposure may be related to statistically significant ALT and AST serum levels increment as well as with increased BMI, while the phthalate levels in the urine may be correlated with increased TG and decreased HDL cholesterol serum levels and associated with indicators of cardiometabolic risk and insulin resistance as LAP and VAI.
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Affiliation(s)
- Nataša Milošević
- Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad, Serbia
| | - Nataša Milić
- Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad, Serbia.
| | | | - Ivana Bajkin
- Faculty of Medicine, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Vojvodina, University of Novi Sad, Novi Sad, Serbia
| | - Ivanka Perčić
- Faculty of Medicine, Clinic for Haematology, Clinical Center of Vojvodina, University of Novi Sad, Novi Sad, Serbia
| | - Ludovico Abenavoli
- Department of Health Sciences, University Magna Graecia, Catanzaro, Italy
| | - Milica Medić Stojanoska
- Faculty of Medicine, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Vojvodina, University of Novi Sad, Novi Sad, Serbia
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40
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Wang S, Wang Y, Pan MH, Ho CT. Anti-obesity molecular mechanism of soy isoflavones: weaving the way to new therapeutic routes. Food Funct 2017; 8:3831-3846. [PMID: 29043346 DOI: 10.1039/c7fo01094j] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Obesity is ringing alarm bells globally. Advances in food science and nutrition research have been devoted to identifying food components that exert anti-obesity effects, as well as investigating the molecular mechanisms by which they modulate the progression of obesity. Soy foods have attracted much interest as high-protein components of the human diet and as unique sources of isoflavones. As they have similar chemical structures to endogenous estrogens, isoflavones are believed to interact with intracellular estrogen receptors, which results in reductions in the accumulation of lipids and the distribution of adipose tissue. Both in vitro and in vivo studies have revealed other signaling pathways in which isoflavones are involved in the inhibition of adipogenesis and lipogenesis by interacting with various transcription factors and upstream signaling molecules. Although the biological mechanisms that cause the biphasic effects of isoflavones and various controversial results remain unknown, it is noteworthy that isoflavones exhibit pleiotropic effects in the human body to regulate metabolism and balance, which may potentially prevent and treat obesity.
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Affiliation(s)
- Siyu Wang
- Department of Food Science, Rutgers University, New Brunswick, NJ 08901, USA.
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41
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Genistein: Its role in metabolic diseases and cancer. Crit Rev Oncol Hematol 2017; 119:13-22. [PMID: 29065980 DOI: 10.1016/j.critrevonc.2017.09.004] [Citation(s) in RCA: 181] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Revised: 08/23/2017] [Accepted: 09/11/2017] [Indexed: 12/12/2022] Open
Abstract
Genistein is an isoflavone present in soy and is known to have multiple molecular effects, such as the inhibition of inflammation, promotion of apoptosis, and modulation of steroidal hormone receptors and metabolic pathways. Since these molecular effects impact carcinogenesis, cancer propagation, obesity, osteoporosis, and metabolic syndromes, genistein plays an important role in preventing and treating common disorders. The role of genistein has not been adequately evaluated in all these clinical settings. This review summarizes some of the known molecular effects of genistein and its potential role in health maintenance and treatment.
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42
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Liu H, Zhong H, Yin Y, Jiang Z. Genistein has beneficial effects on hepatic steatosis in high fat-high sucrose diet-treated rats. Biomed Pharmacother 2017; 91:964-969. [PMID: 28514835 DOI: 10.1016/j.biopha.2017.04.130] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Revised: 04/25/2017] [Accepted: 04/30/2017] [Indexed: 02/07/2023] Open
Abstract
Genistein, a kind of phytoestrogen abundant in soybeans, is beneficial for alleviating non-alcoholic fatty liver disease (NAFLD), but the specific mechanism was not clearly understood. This study was designed to determine the effect of genistein on NAFLD and explore the possible mechanism. 36 male Sprague-Dawley rats were divided into 4 groups: the control group, high fat-high sucrose diet (HFS) group, HFS with 4mg/kg body weight genistein, and HFS with 8mg/kg body weight genistein. 12 weeks later, serum and hepatic lipid profiles, liver histopathological examination were characterized. The protein levels of liver AMP-activated protein kinase (AMPK), phosphorylation of AMPK (p-AMPK), acetyl-CoA carboxylase (ACC), phosphorylation of ACC (p-ACC) and sterol regulatory element binding protein 1 (SREBP-1) were determined by western blot. mRNA expressions of fatty acid synthase gene (FAS) and glycerol-3-phosphate acyltransferase (GPAT), peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyl transfer enzyme-1 (CPT-1) and acyl-CoA oxidase (ACO) were measured by reverse transcription polymerase chain reaction (RT-PCR). Results showed that genistein effectively improved serum and hepatic lipid metabolism and diminished fat accumulation in liver. And the protein level of hepatic p-AMPK and p-ACC were increased, but SREBP-1 was decreased by genistein. Meanwhile, the mRNA levels of FAS and GPAT were lower, but PPARα, CPT-1, ACO were higher in rats treated with genistein compared with HFS group. Collectively, genistein can improve hepatic steatosis via activating AMPK, thus promoting fatty acid oxidation and inhibiting lipid synthesis in liver.
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Affiliation(s)
- Huanhuan Liu
- Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, China
| | - Huijia Zhong
- Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, China
| | - Yimin Yin
- Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, China
| | - Zhuoqin Jiang
- Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, China.
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43
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Xu Z, Liu J, Wu X, Huang B, Pan X. Nonmonotonic responses to low doses of xenoestrogens: A review. ENVIRONMENTAL RESEARCH 2017; 155:199-207. [PMID: 28231547 DOI: 10.1016/j.envres.2017.02.018] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/04/2016] [Revised: 01/13/2017] [Accepted: 02/16/2017] [Indexed: 05/21/2023]
Abstract
Xenoestrogens (XEs) mimic or block the synthesis, metabolism and transport of normal endogenous hormones, disturbing normal endocrine function. The available data on the nonmonotonic estrogenic effects of low doses of many XEs are reviewed, covering in vitro, in vivo and epidemiological studies. The observed nonmonotonic patterns of the dose-response curves are discussed, along with possible underlying mechanisms. This review is intended to provide guidance for harm predication and to suggest prevention measures.
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Affiliation(s)
- Zhixiang Xu
- Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, Yunnan, China
| | - Jun Liu
- Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, Yunnan, China
| | - Xinhao Wu
- Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, Yunnan, China
| | - Bin Huang
- Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, Yunnan, China.
| | - Xuejun Pan
- Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, Yunnan, China
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44
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Martel J, Ojcius DM, Chang CJ, Lin CS, Lu CC, Ko YF, Tseng SF, Lai HC, Young JD. Anti-obesogenic and antidiabetic effects of plants and mushrooms. Nat Rev Endocrinol 2017; 13:149-160. [PMID: 27636731 DOI: 10.1038/nrendo.2016.142] [Citation(s) in RCA: 192] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Obesity is reaching global epidemic proportions as a result of factors such as high-calorie diets and lack of physical exercise. Obesity is now considered to be a medical condition, which not only contributes to the risk of developing type 2 diabetes mellitus, cardiovascular disease and cancer, but also negatively affects longevity and quality of life. To combat this epidemic, anti-obesogenic approaches are required that are safe, widely available and inexpensive. Several plants and mushrooms that are consumed in traditional Chinese medicine or as nutraceuticals contain antioxidants, fibre and other phytochemicals, and have anti-obesogenic and antidiabetic effects through the modulation of diverse cellular and physiological pathways. These effects include appetite reduction, modulation of lipid absorption and metabolism, enhancement of insulin sensitivity, thermogenesis and changes in the gut microbiota. In this Review, we describe the molecular mechanisms that underlie the anti-obesogenic and antidiabetic effects of these plants and mushrooms, and propose that combining these food items with existing anti-obesogenic approaches might help to reduce obesity and its complications.
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Affiliation(s)
- Jan Martel
- Center for Molecular and Clinical Immunology, Chang Gung University, 259 Wen-Hua First Road, Taoyuan 33302, Taiwan, Republic of China
- Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Taoyuan 33305, Taiwan, Republic of China
| | - David M Ojcius
- Center for Molecular and Clinical Immunology, Chang Gung University, 259 Wen-Hua First Road, Taoyuan 33302, Taiwan, Republic of China
- Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Taoyuan 33305, Taiwan, Republic of China
- Department of Biomedical Sciences, University of the Pacific, Arthur Dugoni School of Dentistry, 155 Fifth Street, San Francisco, California 94103, USA
| | - Chih-Jung Chang
- Center for Molecular and Clinical Immunology, Chang Gung University, 259 Wen-Hua First Road, Taoyuan 33302, Taiwan, Republic of China
- Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Taoyuan 33305, Taiwan, Republic of China
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, 259 Wen-Hua First Road, Taoyuan 33302, Taiwan, Republic of China
- Department of Microbiology and Immunology, Chang Gung University, 259 Wen-Hua First Road, Taoyuan 33302, Taiwan, Republic of China
- Research Center of Bacterial Pathogenesis, Chang Gung University, 259 Wen-Hua First Road, Taoyuan 33302, Taiwan, Republic of China
| | - Chuan-Sheng Lin
- Center for Molecular and Clinical Immunology, Chang Gung University, 259 Wen-Hua First Road, Taoyuan 33302, Taiwan, Republic of China
- Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Taoyuan 33305, Taiwan, Republic of China
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, 259 Wen-Hua First Road, Taoyuan 33302, Taiwan, Republic of China
- Department of Microbiology and Immunology, Chang Gung University, 259 Wen-Hua First Road, Taoyuan 33302, Taiwan, Republic of China
- Research Center of Bacterial Pathogenesis, Chang Gung University, 259 Wen-Hua First Road, Taoyuan 33302, Taiwan, Republic of China
| | - Chia-Chen Lu
- Department of Respiratory Therapy, Fu Jen Catholic University, 510 Zhong-Zheng Street, New Taipei City 24205, Taiwan, Republic of China
| | - Yun-Fei Ko
- Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Taoyuan 33305, Taiwan, Republic of China
- Chang Gung Biotechnology Corporation, 201 Tung-Hua North Road, Taipei 10508, Taiwan, Republic of China
- Biochemical Engineering Research Center, Ming Chi University of Technology, 84 Gungjuan Road, New Taipei City 24301, Taiwan, Republic of China
| | - Shun-Fu Tseng
- Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Taoyuan 33305, Taiwan, Republic of China
- Research Center of Bacterial Pathogenesis, Chang Gung University, 259 Wen-Hua First Road, Taoyuan 33302, Taiwan, Republic of China
| | - Hsin-Chih Lai
- Center for Molecular and Clinical Immunology, Chang Gung University, 259 Wen-Hua First Road, Taoyuan 33302, Taiwan, Republic of China
- Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Taoyuan 33305, Taiwan, Republic of China
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, 259 Wen-Hua First Road, Taoyuan 33302, Taiwan, Republic of China
- Department of Microbiology and Immunology, Chang Gung University, 259 Wen-Hua First Road, Taoyuan 33302, Taiwan, Republic of China
- Research Center of Bacterial Pathogenesis, Chang Gung University, 259 Wen-Hua First Road, Taoyuan 33302, Taiwan, Republic of China
- Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Taoyuan 33305, Taiwan, Republic of China
- Research Center for Industry of Human Ecology, College of Human Ecology, Chang Gung University of Science and Technology, 261 Wen-Hua First Road, Taoyuan 33303, Taiwan, Republic of China
- Graduate Institute of Health Industry and Technology, College of Human Ecology, Chang Gung University of Science and Technology, 261 Wen-Hua First Road, Taoyuan 33303, Taiwan, Republic of China
| | - John D Young
- Center for Molecular and Clinical Immunology, Chang Gung University, 259 Wen-Hua First Road, Taoyuan 33302, Taiwan, Republic of China
- Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Taoyuan 33305, Taiwan, Republic of China
- Chang Gung Biotechnology Corporation, 201 Tung-Hua North Road, Taipei 10508, Taiwan, Republic of China
- Biochemical Engineering Research Center, Ming Chi University of Technology, 84 Gungjuan Road, New Taipei City 24301, Taiwan, Republic of China
- Laboratory of Cellular Physiology and Immunology, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
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Abstract
PURPOSE OF REVIEW The purpose of this review was to summarise current evidence that some environmental chemicals may be able to interfere in the endocrine regulation of energy metabolism and adipose tissue structure. RECENT FINDINGS Recent findings demonstrate that such endocrine-disrupting chemicals, termed "obesogens", can promote adipogenesis and cause weight gain. This includes compounds to which the human population is exposed in daily life through their use in pesticides/herbicides, industrial and household products, plastics, detergents, flame retardants and as ingredients in personal care products. Animal models and epidemiological studies have shown that an especially sensitive time for exposure is in utero or the neonatal period. In summarising the actions of obesogens, it is noteworthy that as their structures are mainly lipophilic, their ability to increase fat deposition has the added consequence of increasing the capacity for their own retention. This has the potential for a vicious spiral not only of increasing obesity but also increasing the retention of other lipophilic pollutant chemicals with an even broader range of adverse actions. This might offer an explanation as to why obesity is an underlying risk factor for so many diseases including cancer.
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Affiliation(s)
- Philippa D Darbre
- School of Biological Sciences, University of Reading, Reading, RG6 6UB, UK.
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46
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Milošević N, Jakšić V, Sudji J, Vuković B, Ičin T, Milić N, Medić Stojanoska M. Possible influence of the environmental pollutant bisphenol A on the cardiometabolic risk factors. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2017; 27:11-26. [PMID: 27771963 DOI: 10.1080/09603123.2016.1246654] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Abstract
Bisphenol A (BPA) is a ubiquitous environmental pollutant which is often associated with various health issues. In this study 103 healthy female volunteers in reproductive age from Serbian north province Vojvodina were enrolled and examined for the BPA exposure in the urine samples after 12 h of fasting. BPA was found in 35.92 % (37/103) of subjects. Statistically significant increment in waist circumference (p = 0.045) and waist-to-height ratio (p = 0.037) was observed among the BPA positive women in comparison with the women who had the same energetic balance and had not been exposed to BPA. Linear correlation was obtained between the BPA concentration in urine samples and body mass index (r2 = 0.35, p = 0.003) waist circumference (r2 = 0.21, p = 0.02) and waist-to-height ratio (r2 = 0.25, p = 0.01) among the obese. High energetic intake and reduced physical activity additionally pronounced BPA positive association with obesity. No statistically significant difference was observed in triglycerides, HDL and LDL cholesterol levels between the BPA exposed and BPA non-exposed female volunteers.
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Affiliation(s)
- Nataša Milošević
- a Faculty of Medicine, Department of Pharmacy , University of Novi Sad , Novi Sad , Serbia
| | - Vladimir Jakšić
- b Faculty of Medicine , University of Novi Sad , Novi Sad , Serbia
| | - Jan Sudji
- a Faculty of Medicine, Department of Pharmacy , University of Novi Sad , Novi Sad , Serbia
| | - Bojan Vuković
- c Faculty of Medicine , Clinical Center of Vojvodina, Emergency Center, University of Novi Sad , Novi Sad , Serbia
| | - Tijana Ičin
- d Faculty of Medicine, Clinic for Endocrinology, Diabetes and Metabolic Diseases , Clinical Center of Vojvodina, University of Novi Sad , Novi Sad , Serbia
| | - Nataša Milić
- a Faculty of Medicine, Department of Pharmacy , University of Novi Sad , Novi Sad , Serbia
| | - Milica Medić Stojanoska
- d Faculty of Medicine, Clinic for Endocrinology, Diabetes and Metabolic Diseases , Clinical Center of Vojvodina, University of Novi Sad , Novi Sad , Serbia
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47
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Aziz SA, Wakeling LA, Miwa S, Alberdi G, Hesketh JE, Ford D. Metabolic programming of a beige adipocyte phenotype by genistein. Mol Nutr Food Res 2017; 61:1600574. [PMID: 27670404 PMCID: PMC5299525 DOI: 10.1002/mnfr.201600574] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2016] [Revised: 08/31/2016] [Accepted: 09/11/2016] [Indexed: 11/10/2022]
Abstract
SCOPE Promoting the development of brown or beige adipose tissue may protect against obesity and related metabolic features, and potentially underlies protective effects of genistein in mice. METHODS AND RESULTS We observed that application of genistein to 3T3-L1 adipocytes changed the lipid distribution from large droplets to a multilocular distribution, reduced mRNAs indicative of white adipocytes (ACC, Fasn, Fabp4, HSL, chemerin, and resistin) and increased mRNAs that are a characteristic feature of brown/beige adipocytes (CD-137 and UCP1). Transcripts with a role in adipocyte differentiation (Cebpβ, Pgc1α, Sirt1) peaked at different times after application of genistein. These responses were not affected by the estrogen receptor (ER) antagonist fulvestrant, revealing that this action of genistein is not through the classical ER pathway. The Sirt1 inhibitor Ex-527 curtailed the genistein-mediated increase in UCP1 and Cebpβ mRNA, revealing a role for Sirt1 in mediating the effect. Baseline oxygen consumption and the proportional contribution of proton leak to maximal respiratory capacity was greater for cells exposed to genistein, demonstrating greater mitochondrial uncoupling. CONCLUSIONS We conclude that genistein acts directly on adipocytes or on adipocyte progenitor cells to programme the cells metabolically to adopt features of beige adipocytes. Thus, this natural dietary agent may protect against obesity and related metabolic disease.
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Affiliation(s)
- Sadat A. Aziz
- Institute for Cell and Molecular BiosciencesNewcastle upon TyneUK
| | | | - Satomi Miwa
- Institute for Cell and Molecular BiosciencesNewcastle upon TyneUK
| | - Goiuri Alberdi
- Department of Obstetrics and GynaecologyUniversity College DublinDublinUK
| | - John E. Hesketh
- Institute for Cell and Molecular BiosciencesNewcastle upon TyneUK
| | - Dianne Ford
- Faculty of Health and Life SciencesNorthumbria UniversityNewcastle upon TyneUK
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Müller DR, Soukup ST, Kurrat A, Liu X, Schmicke M, Xie MY, Kulling SE, Diel P. Neonatal isoflavone exposure interferes with the reproductive system of female Wistar rats. Toxicol Lett 2016; 262:39-48. [PMID: 27506417 DOI: 10.1016/j.toxlet.2016.08.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 07/29/2016] [Accepted: 08/05/2016] [Indexed: 12/20/2022]
Abstract
There is increasing concern about possible adverse effects of soy based infant formulas (SBIF) due to their high amount of isoflavones (ISO). The aim of the present study was to investigate effects of neonatal exposure to ISO on reproductive system of female Wistar rats. Animals were exposed to an ISO depleted diet or a diet enriched with an ISO extract (IRD; 508mg ISO/kg) during embryogenesis and adolescence. Pups of each group were fed daily by pipette with ISO-suspension (ISO+; 32mg ISO/kg bw) or placebo from postnatal day (PND) 1 until PND23 resulting in plasma concentrations similar to levels reported in infants fed SBIF. The visceral fat mass was reduced by long-term IRD. Vaginal epithelial height was increased at PND23 and vaginal opening was precocious in ISO+ groups. Later in life, more often irregular estrus cycles were observed in rats of ISO+ groups. In addition, FSH levels and uterine epithelial heights were increased at PND80 in ISO+ groups. In summary, the results indicate that neonatal ISO intake, resulting in plasma concentrations achievable through SBIF, has an estrogenic effect on prepubertal rats and influences female reproductive tract later in life.
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Affiliation(s)
- Dennis R Müller
- Institute of Cardiovascular Research and Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sport University, Cologne, Germany
| | - Sebastian T Soukup
- Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Karlsruhe, Germany, Germany
| | - Anne Kurrat
- Institute of Cardiovascular Research and Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sport University, Cologne, Germany
| | - Xin Liu
- State Key Laboratory of Food Science and Technology, Nanchang University, China
| | - Marion Schmicke
- Clinic for Cattle, Endocrinology, University of Veterinary Medicine, Hannover, Germany
| | - Ming-Yong Xie
- State Key Laboratory of Food Science and Technology, Nanchang University, China
| | - Sabine E Kulling
- Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Karlsruhe, Germany, Germany
| | - Patrick Diel
- Institute of Cardiovascular Research and Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sport University, Cologne, Germany.
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Adeogun AO, Ibor OR, Onoja AB, Arukwe A. Fish condition factor, peroxisome proliferator activated receptors and biotransformation responses in Sarotherodon melanotheron from a contaminated freshwater dam (Awba Dam) in Ibadan, Nigeria. MARINE ENVIRONMENTAL RESEARCH 2016; 121:74-86. [PMID: 26898991 DOI: 10.1016/j.marenvres.2016.02.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2015] [Revised: 01/31/2016] [Accepted: 02/03/2016] [Indexed: 06/05/2023]
Abstract
The relationship between condition factor (CF), peroxisome proliferator-activated receptors (PPARs), phase 1 biotransformation (CYP1A isoforms) and contaminant burden has been studied in Sarotherodon melanotheron from a contaminated tropical freshwater dam (Awba Dam) and compared to a reference site (Modete Dam) in Southwest, Nigeria. A total of 89 fish (57 males and 32 females) was collected from Awba Dam and 95 fish (48 males and 47 females) from the reference site. In general, fish sampled from Awba Dam were bigger than reference site. Sediment samples were also collected from both sites for contaminant analysis. Expression of ppar and cyp1 isoforms was analyzed using validated real-time PCR, while CYP1A and PPAR protein levels were analyzed using immunochemical method with specific antibodies. CYP-mediated catalytic responses (EROD, MROD and BROD) were performed by biochemical methods. We observed significant increases in ppar and cyp1 isoforms mRNA in both male and female fish from Awba Dam, compared to the reference site. Catalytic activities of EROD, MROD and BROD paralleled cyp1 transcript levels. Sex-related differences in PPAR and CYP1A protein levels were also observed, showing higher CYP1A proteins in males, compared with females, and higher PPAR proteins in females compared with males. Principal component analysis (PCA) biplot showed positive relationships between biological responses (ppar isoforms), condition factor (CF) and sediment PCBs, PAHs, OCPs and heavy metal concentrations. The present study shows that S. melanotheron inhabiting Awba Dam are severely affected by different classes of environmental contaminants that target metabolic processes (PPAR) and biotransformation pathways (CYP1A) in male and female fish, compared to a reference site. Interestingly, fish from Awba Dam were exhibiting good growth (evidence by high CF values) that paralleled increases in the transcriptional activation of ppar and cyp1 isoforms, despite the high contaminant burdens, suggesting a possible contaminant-induced obesogenic effects.
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Affiliation(s)
- Aina O Adeogun
- Department of Zoology, University of Ibadan, Ibadan, Nigeria
| | - Oju R Ibor
- Department of Zoology, University of Ibadan, Ibadan, Nigeria
| | - Anyebe B Onoja
- Department of Virology, University of Ibadan, Ibadan, Nigeria
| | - Augustine Arukwe
- Department of Biology, Norwegian University of Science and Technology (NTNU), Høgskoleringen 5, N-7491 Trondheim, Norway.
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