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Zhao Y, Yue R. White adipose tissue in type 2 diabetes and the effect of antidiabetic drugs. Diabetol Metab Syndr 2025; 17:116. [PMID: 40186308 PMCID: PMC11969724 DOI: 10.1186/s13098-025-01678-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 03/19/2025] [Indexed: 04/07/2025] Open
Abstract
White adipose tissue (WAT) is highly flexible and was previously considered a passive location for energy storage. Its endocrine function has been established for several years, earning it the title of an "endocrine organ" due to its ability to secrete many adipokines that regulate metabolism. WAT is one of the core tissues that influence insulin sensitivity. Its dysfunction enhances insulin resistance and type 2 diabetes (T2D) progression. However, T2D may cause WAT dysfunction, including changes in distribution, metabolism, adipocyte hypertrophy, inflammation, aging, and adipokines and free fatty acid levels, which may exacerbate insulin resistance. This review used PubMed to search WAT dysfunction in T2D and the effects of these changes on insulin resistance. Additionally, we described and discussed the effects of antidiabetic drugs, including insulin therapy, sulfonylureas, metformin, glucose-like peptide-1 receptor agonists, thiazolidinediones, and sodium-dependent glucose transporters-2 inhibitors, on WAT parameters under T2D conditions.
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Affiliation(s)
- Yixuan Zhao
- Chengdu University of Traditional Chinese Medicine, Hospital of Chengdu, University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, Sichuan Province, 610072, P. R. China
| | - Rensong Yue
- Chengdu University of Traditional Chinese Medicine, Hospital of Chengdu, University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, Sichuan Province, 610072, P. R. China.
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Smit ER, Romijn M, Langerhorst P, van der Zwaan C, van der Staaij H, Rotteveel J, van Kaam AH, Fustolo-Gunnink SF, Hoogendijk AJ, Onland W, Finken MJJ, van den Biggelaar M. Distinct protein patterns related to postnatal development in small for gestational age preterm infants. Pediatr Res 2025; 97:1722-1731. [PMID: 39152333 PMCID: PMC12119372 DOI: 10.1038/s41390-024-03481-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 07/18/2024] [Accepted: 07/30/2024] [Indexed: 08/19/2024]
Abstract
BACKGROUND Preterm infants, especially those born small for gestational age (SGA), are at risk of short-term and long-term health complications. Characterization of changes in circulating proteins postnatally in preterm infants may provide valuable fundamental insights into this population. Here, we investigated postnatal developmental patterns in preterm infants and explored protein signatures that deviate between SGA infants and appropriate for gestational age (AGA) infants using a mass spectrometry (MS)-based proteomics workflow. METHODS Longitudinal serum samples obtained at postnatal days 0, 3, 7, 14, and 28 from 67 preterm infants were analyzed using unbiased MS-based proteomics. RESULTS 314 out of 833 quantified serum proteins change postnatally, including previously described age-related changes in immunoglobulins, hemoglobin subunits, and new developmental patterns, e.g. apolipoproteins (APOA4) and terminal complement cascade (C9) proteins. Limited differences between SGA and AGA infants were found at birth while longitudinal monitoring revealed 69 deviating proteins, including insulin-sensitizing hormone adiponectin, platelet proteins, and 24 proteins with an annotated function in the immune response. CONCLUSIONS This study shows the potential of MS-based serum profiling in defining circulating protein trajectories in the preterm infant population and its ability to identify longitudinal alterations in protein levels associated with SGA. IMPACT Postnatal changes of circulating proteins in preterm infants have not fully been elucidated but may contribute to development of health complications. Mass spectrometry-based analysis is an attractive approach to study circulating proteins in preterm infants with limited material. Longitudinal plasma profiling reveals postnatal developmental-related patterns in preterm infants (314/833 proteins) including previously described changes, but also previously unreported proteins. Longitudinal monitoring revealed an immune response signature between SGA and AGA infants. This study highlights the importance of taking postnatal changes into account for translational studies in preterm infants.
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Affiliation(s)
- Eva R Smit
- Department of Molecular Hematology, Sanquin Research, Amsterdam, the Netherlands
| | - Michelle Romijn
- Department of Neonatology, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands
- Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands
- Department of Pediatric Endocrinology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Pieter Langerhorst
- Department of Molecular Hematology, Sanquin Research, Amsterdam, the Netherlands
| | - Carmen van der Zwaan
- Department of Molecular Hematology, Sanquin Research, Amsterdam, the Netherlands
| | - Hilde van der Staaij
- Sanquin Research & Lab Services, Sanquin Blood Supply Foundation, Amsterdam, the Netherlands
- Department of Pediatrics, Division of Neonatology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands
- Department of Pediatric Hematology, Emma Children's Hospital, Amsterdam University Medical Center, Amsterdam, the Netherlands
| | - Joost Rotteveel
- Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands
- Department of Pediatric Endocrinology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Anton H van Kaam
- Department of Neonatology, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands
- Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands
| | - Suzanne F Fustolo-Gunnink
- Sanquin Research & Lab Services, Sanquin Blood Supply Foundation, Amsterdam, the Netherlands
- Department of Pediatrics, Division of Neonatology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands
- Department of Pediatric Hematology, Emma Children's Hospital, Amsterdam University Medical Center, Amsterdam, the Netherlands
| | - Arie J Hoogendijk
- Department of Molecular Hematology, Sanquin Research, Amsterdam, the Netherlands
| | - Wes Onland
- Department of Neonatology, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands
- Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands
| | - Martijn J J Finken
- Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands
- Department of Pediatric Endocrinology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
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Xu B, Liu H, Yang G, Zhang S, Zhou Z, Gao Y. Novel double-layered PLGA microparticles-dissolving microneedle (MPs-DMN) system for peptide drugs sustained release by transdermal delivery. Int J Pharm 2025; 670:125128. [PMID: 39722375 DOI: 10.1016/j.ijpharm.2024.125128] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 12/15/2024] [Accepted: 12/21/2024] [Indexed: 12/28/2024]
Abstract
The combination of microparticles (MPs) with dissolving microneedles (DMN) represents a promising transdermal approach for the sustained release of biomacromolecule drug. In this study, we developed a double-layered microparticles-dissolving microneedle (MPs-DMN) system, which strategically concentrates PLGA MPs at the tip of the microneedle to achieve sustained release of peptide drugs through transdermal delivery. We selected exenatide (EXT) as a model peptide drug and established HPLC-UV and UPLC-MS methods for the quantitative analysis of the drug content of MPs-DMN and drug concentrations in plasma. Ultrasonication was utilized in the first step of the double emulsion solvent evaporation method to produce PLGA microparticles, achieving a high drug loading efficiency of 22.76 ± 0.64 %, surpassing the commercial products. The EXT-loaded microparticles were then mixed with 10 % w/v sucrose solution to form the first layer of the microneedle, and the mixture of the base solution was added to form the double-layered dissolving microneedle. Microscopic analysis revealed that the MPs were predominantly concentrated in the upper 50 % of the microneedle body, resulting in an impressive drug delivery efficiency of 92.86 ± 1.62 %. The MPs-DMN patch demonstrated the capability to 238.20 ± 5.79 μg of EXT within a compact area of 0.75 cm2, surpassing the capacities reported in existing research. The insertion and dissolution assessments exhibited rapid dissolution, maintaining the MPs as an effective drug reservoir within the skin. Pharmacokinetic assessments indicated that the long half-life (T1/2) of 466.4 ± 12.2 h and high relative bioavailability of 89.71 % for MPs-DMN. Furthermore, pharmacodynamic studies indicated that the MPs-DMN effectively controlled blood glucose levels below 20 mmol/L in diabetic (db/db) mouse for two weeks. These promising findings suggest that the MPs-DMN system could serve as a viable transdermal delivery method for the prolonged administration of peptide drugs.
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Affiliation(s)
- Bo Xu
- Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Han Liu
- Beijing CAS Microneedle Technology Ltd., Beijing 102609, China
| | - Guozhong Yang
- Beijing CAS Microneedle Technology Ltd., Beijing 102609, China
| | - Suohui Zhang
- Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China; Beijing CAS Microneedle Technology Ltd., Beijing 102609, China
| | - Zequan Zhou
- Beijing CAS Microneedle Technology Ltd., Beijing 102609, China
| | - Yunhua Gao
- Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China; Beijing CAS Microneedle Technology Ltd., Beijing 102609, China.
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Mohammedsaeed W. Exploring the interplay between DHCR7, vitamin D deficiency, and type 2 diabetes mellitus (T2DM): a systematic review. Mol Biol Rep 2024; 51:1123. [PMID: 39503960 DOI: 10.1007/s11033-024-10072-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 10/28/2024] [Indexed: 11/20/2024]
Abstract
Type 2 diabetes mellitus (T2DM) is a growing global health concern. The pathogenesis of T2DM is multifactorial and intricate, involving a complex interplay of genetic predisposition, environmental factors, and molecular interactions. Vitamin D (circulating 25-hydroxyvitamin D concentration) regulates factors crucial for T2DM, including insulin secretion, sensitivity, and inflammation. Thus, vitamin D deficiency has been linked to poor health outcomes in T2DM patients. The cholesterol-synthesizing enzyme 7-dehydrocholesterol reductase (DHCR7) represents a critical regulatory switch between cholesterol and vitamin D3 synthesis. Recent findings suggest that the enzyme DHCR7 may indicate T2DM glycolipid metabolic disorder and is associated with deficient circulating vitamin D (circulating 25-hydroxyvitamin D concentration) status. In this PRISMA-guided systematic review, articles were sourced from two databases, namely, PubMed and Cochrane Library, to evaluate the impact of vitamin D deficiency in patients with T2DM and to explore the emerging role of DHCR7 in T2DM pathogenesis. Our findings strongly indicate a positive correlation between deficient vitamin D status and poor health outcomes in T2DM patients. Finally, this systematic review presents a novel perspective on T2DM development, focusing on the interplay between T2DM-associated hyperglycemia, expression of DHCR7, and abrogation of vitamin D synthesis.
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Affiliation(s)
- Walaa Mohammedsaeed
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Science, Taibah University, 344, Postal Code 3000, Al-Madinah, Saudi Arabia.
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Qiu S, Li C, Zhu J, Guo Z. Associations between the TyG index and the ɑ-Klotho protein in middle-aged and older population relevant to diabetes mellitus in NHANES 2007-2016. Lipids Health Dis 2024; 23:188. [PMID: 38907289 PMCID: PMC11191244 DOI: 10.1186/s12944-024-02172-3] [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: 03/29/2024] [Accepted: 05/31/2024] [Indexed: 06/23/2024] Open
Abstract
BACKGROUND The anti-aging protein Klotho has diverse functions in antioxidative stress and energy metabolism through several pathways. While it has been reported that α-Klotho is downregulated in patients with insulin resistance (IR), the association between Klotho and IR is complex and controversial. The triglyceride-glucose (TyG) index has provided a practical method for assessing IR. With this in mind, our study aimed to investigate the relationship between the TyG index and soluble α-Klotho protein levels in US populations, both with and without diabetes mellitus. METHODS This cross-sectional study analyzed data from middle-aged and older participants in the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2016. The participants were divided into two groups based on their diabetes mellitus status: those with diabetes and those without diabetes. To evaluate the relationship between the TyG index and the concentration of the α-Klotho protein in each group, a series of survey-weighted multivariable linear regression models were employed. Furthermore, to examine the association between these two variables, multivariable-adjusted restricted cubic spline curves and subgroup analysis were generated. RESULTS The study involved 6,439 adults aged 40 years or older, with a mean age of 57.8 ± 10.9 years. Among them, 1577 (24.5%) had diabetes mellitus. A subgroup analysis indicated that the presence of diabetes significantly affected the relationship between the TyG index and the α-Klotho level. After considering all covariables, regression analysis of the participants without diabetes revealed that the α-Klotho concentration decreased by 32.35 pg/ml (95% CI: -50.07, -14.64) with each one unit increase in TyG (p < 0.001). The decline in α-Klotho levels with elevated TyG was more pronounced in the female population. In patients with diabetes mellitus, a non-linear association between the TyG index and α-Klotho was observed. There was no significant correlation observed between the two when TyG index were below 9.7. However, there was an increase in klotho levels of 106.44 pg/ml for each unit increase in TyG index above 9.7 (95% CI: 28.13, 184.74) (p = 0.008). CONCLUSION Our findings suggested that the presence of diabetes may influence the relationship between the TyG index and soluble α-Klotho. Furthermore, there seem to be sex differences in individuals without diabetes. Further studies are necessary to validate these findings.
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Affiliation(s)
- Shujuan Qiu
- Department of Nephrology, Affiliated Hospital of Shandong Second Medical University, No. 2428, Yuhe Road, Quiwen District, Weifang, 261041, Shandong, China.
| | - Chunlei Li
- Department of Nephrology, Affiliated Hospital of Shandong Second Medical University, No. 2428, Yuhe Road, Quiwen District, Weifang, 261041, Shandong, China
| | - Jinhua Zhu
- Zhucheng Nanhu Community Health Service Center, No. 2000, Tourism Road, South Lake Ecological Economic Development District, Zhucheng, 262200, Shandong, China
| | - Zhentao Guo
- Department of Nephrology, Affiliated Hospital of Shandong Second Medical University, No. 2428, Yuhe Road, Quiwen District, Weifang, 261041, Shandong, China
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Su Z, Efremov L, Mikolajczyk R. Differences in the levels of inflammatory markers between metabolically healthy obese and other obesity phenotypes in adults: A systematic review and meta-analysis. Nutr Metab Cardiovasc Dis 2024; 34:251-269. [PMID: 37968171 DOI: 10.1016/j.numecd.2023.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 07/28/2023] [Accepted: 09/04/2023] [Indexed: 11/17/2023]
Abstract
AIMS The aim of this study was to systematically review and analyze differences in the levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) comparing metabolically healthy but obese (MHO) with metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO) subjects. DATA SYNTHESIS We searched PubMed, Embase, Web of Science, and Scopus for studies that matched the relevant search terms. Differences in inflammatory marker levels between MHO and the other three phenotypes were pooled as standardized mean differences (SMD) or differences of medians (DM) using a random-effects model. We included 91 studies reporting data on 435,007 individuals. The CRP levels were higher in MHO than in MHNO subjects (SMD = 0.63, 95% CI: 0.49, 0.76; DM = 0.83 mg/L, 95% CI: 0.56, 1.11). The CRP levels were higher in MHO than in MUNO subjects (SMD = 0.16, 95% CI: 0.05, 0.28; DM = 0.39 mg/L, 95% CI: 0.09, 0.69). The CRP levels were lower in MHO than in MUO individuals (SMD = -0.43, 95% CI: -0.54, -0.31; DM = -0.82 mg/L, 95% CI: -1.16, -0.48). The IL-6 levels in MHO were higher than in MHNO while lower than in MUO subjects. The TNF-α levels in MHO were higher than in MHNO individuals. CONCLUSIONS This review provides evidence that CRP levels in MHO are higher than in MHNO and MUNO subjects but lower than in MUO individuals. Additionally, IL-6 levels in MHO are higher than in MHNO but lower than in MUO subjects, and TNF-α levels in MHO are higher than in MHNO individuals. SYSTEMATIC REVIEW REGISTRATION PROSPERO number: CRD42021234948.
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Affiliation(s)
- Zhouli Su
- Institute for Medical Epidemiology, Biometrics and Informatics (IMEBI), Interdisciplinary Center for Health Sciences, Martin-Luther-University Halle-Wittenberg, D-06112 Halle (Saale), Germany
| | - Ljupcho Efremov
- Institute for Medical Epidemiology, Biometrics and Informatics (IMEBI), Interdisciplinary Center for Health Sciences, Martin-Luther-University Halle-Wittenberg, D-06112 Halle (Saale), Germany; Department of Radiation Oncology, Martin-Luther-University Halle-Wittenberg, D-06120 Halle (Saale), Germany
| | - Rafael Mikolajczyk
- Institute for Medical Epidemiology, Biometrics and Informatics (IMEBI), Interdisciplinary Center for Health Sciences, Martin-Luther-University Halle-Wittenberg, D-06112 Halle (Saale), Germany.
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Laha N, Huey N, Coull B, Mukherjee R. On statistical inference with high-dimensional sparse CCA. INFORMATION AND INFERENCE : A JOURNAL OF THE IMA 2023; 12:iaad040. [PMID: 37982049 PMCID: PMC10656287 DOI: 10.1093/imaiai/iaad040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 04/12/2023] [Accepted: 09/08/2023] [Indexed: 11/21/2023]
Abstract
We consider asymptotically exact inference on the leading canonical correlation directions and strengths between two high-dimensional vectors under sparsity restrictions. In this regard, our main contribution is developing a novel representation of the Canonical Correlation Analysis problem, based on which one can operationalize a one-step bias correction on reasonable initial estimators. Our analytic results in this regard are adaptive over suitable structural restrictions of the high-dimensional nuisance parameters, which, in this set-up, correspond to the covariance matrices of the variables of interest. We further supplement the theoretical guarantees behind our procedures with extensive numerical studies.
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Affiliation(s)
- Nilanjana Laha
- Department of Statistics, Texas A&M, College Station, TX 77843, USA
| | - Nathan Huey
- Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
| | - Brent Coull
- Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
| | - Rajarshi Mukherjee
- Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
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Abdelrahman BA, El-Khatib AS, Attia YM. Insights into the role of vitamin D in targeting the culprits of non-alcoholic fatty liver disease. Life Sci 2023; 332:122124. [PMID: 37742738 DOI: 10.1016/j.lfs.2023.122124] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 09/12/2023] [Accepted: 09/21/2023] [Indexed: 09/26/2023]
Abstract
Vitamin D (VD) is a secosteroid hormone that is renowned for its crucial role in phospho-calcium homeostasis upon binding to the nuclear vitamin D receptor (VDR). Over and above, the pleiotropic immunomodulatory, anti-inflammatory, and metabolic roles VD plays in different disease settings started to surface in the past few decades. On the other hand, a growing body of evidence suggests a correlation between non-alcoholic fatty liver disease (NAFLD) and its progressive inflammatory form non-alcoholic steatohepatitis (NASH) with vitamin D deficiency (VDD) owing to the former's ingrained link with obesity and metabolic syndrome. Accordingly, a better understanding of the contribution of disrupted VDR signalling to NAFLD incidence and progression would provide further insights into its diagnosis, treatment modalities, and prognosis. This is especially significant as, hitherto, no drug for NAFLD has been approved. This review, therefore, sought to set forth the likely contribution of VDR signalling in NAFLD and how it might influence its multiple drivers.
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Affiliation(s)
- Basma A Abdelrahman
- Department of Pharmacology, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt; The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt
| | - Aiman S El-Khatib
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
| | - Yasmeen M Attia
- Department of Pharmacology, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt; The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt
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Son D, Lee M. Gene regulation of RMR-related DNAJC6 on adipogenesis and mitochondria function in 3T3-L1 preadipocytes. Biochem Biophys Res Commun 2023; 672:1-9. [PMID: 37331165 DOI: 10.1016/j.bbrc.2023.06.037] [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: 05/26/2023] [Revised: 06/06/2023] [Accepted: 06/11/2023] [Indexed: 06/20/2023]
Abstract
In the pilot GWAS of children obesity, DNAJC6 gene was found as a regulator for resting metabolic rate (RMR) and obesity in children aged 8-9 years. To investigate whether DNAJC6 gene regulated obesity and energy metabolism, the physiological mechanisms during adipogenesis of 3T3-L1 preadipocytes were confirmed after DNAJC6 gene was overexpressed or inhibited. Overexpressing DNAJC6 gene maintained a 3T3-L1 preadipocyte status during cell differentiation (MTT, ORO, DAPI/BODIPY). It suppressed adipogenesis and adipokine production (leptin, adiponectin), insulin signaling with IRS-GLUT4 system (RT-PCR, Western blotting), and mitochondrial function (Mito Stress Test). DNAJC6 overexpressed cells inhibited mTOR expression, but maintained LC3 expression at a high level, indicating that autophagy occurred and energy was obtained. However, when DNAJC6 gene was inhibited, fat synthesis factor was highly expressed during differentiation (PPARr, C/EBPa, aP2, etc) and the intracellular stress level increased accordingly, which affected the reduction of reserve respiratory capacity during mitochondrial respiration. Our study confirmed gene regulation of DNAJC6, overexpression or inhibition, affects adipogenesis with energy metabolism and mitochondrial functions. This basic data can be used for clinic obesity studies to control an energy imbalance.
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Affiliation(s)
- Dajeong Son
- Department of Food & Nutrition, Sungshin Women's University, Seoul, 01133, Republic of Korea; Research Institute of Obesity Science, Sungshin Women's University, Seoul, 01133, Republic of Korea
| | - Myougsook Lee
- Department of Food & Nutrition, Sungshin Women's University, Seoul, 01133, Republic of Korea; Research Institute of Obesity Science, Sungshin Women's University, Seoul, 01133, Republic of Korea.
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Sharma P, Sri Swetha Victoria V, Praneeth Kumar P, Karmakar S, Swetha M, Reddy A. Cross-talk between insulin resistance and nitrogen species in hypoxia leads to deterioration of tissue and homeostasis. Int Immunopharmacol 2023; 122:110472. [PMID: 37392570 DOI: 10.1016/j.intimp.2023.110472] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 05/19/2023] [Accepted: 06/07/2023] [Indexed: 07/03/2023]
Abstract
Hypoxia has been linked with insulin resistance as it produces changes in the metabolism of the cell; in which the adipocytes impede the insulin receptor tyrosine, phosphorylation, directing at decreased levels of transport of glucose. At this juncture, we are focusing on cross-talk between insulin resistance and nitrogen species in hypoxia, leading to the deterioration of tissue and homeostasis. Physiological levels of nitric oxide play a very crucial role in acting as a priority effector and signaling molecule, arbitrating the body's responses to hypoxia. Both ROS and RNS are associated with a reduction in IRS1 phosphorylation in tyrosine, which leads to reduced levels of IRS1 content and insulin response, which further leads to insulin resistance. Cellular hypoxia is a trigger to inflammatory mediators which signal tissue impairment and initiate survival requirements. But, hypoxia-mediated inflammation act as a protective role by an immune response and promotes wound healing during infection. In this review, we abridge the crosstalk between the inflammation and highlight the dysregulation in physiological consequences due to diabetes mellitus. Finally, we review various treatments available for its related physiological complications.
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Affiliation(s)
- Priyanshy Sharma
- Animal Cell Culture Laboratory, Department of Biotechnology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nādu, India
| | - V Sri Swetha Victoria
- Animal Cell Culture Laboratory, Department of Biotechnology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nādu, India
| | - P Praneeth Kumar
- Animal Cell Culture Laboratory, Department of Biotechnology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nādu, India
| | - Sarbani Karmakar
- Animal Cell Culture Laboratory, Department of Biotechnology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nādu, India
| | - Mudduluru Swetha
- Animal Cell Culture Laboratory, Department of Biotechnology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nādu, India
| | - Amala Reddy
- Animal Cell Culture Laboratory, Department of Biotechnology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nādu, India.
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Gupta A, Gupta P, Singh AK, Gupta V. Association of adipokines with insulin resistance and metabolic syndrome including obesity and diabetes. GHM OPEN 2023; 3:7-19. [PMID: 40143837 PMCID: PMC11933950 DOI: 10.35772/ghmo.2023.01004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 07/18/2023] [Accepted: 07/25/2023] [Indexed: 03/28/2025]
Abstract
Adipose tissue (AT) acts as a highly active endocrine organ, which secretes a wide range of adipokine hormones. In the past few years, several adipokines (leptin, adiponectin, resistin etc.) have been discovered showing metabolic consequences in relation to insulin resistance (IR), obesity and diabetes. These adipokines are considered to be an important component playing an important role in the regulation of energy metabolism. They have been shown to be involved in the pathogenesis of metabolic syndrome (MetS) and cardiac diseases. The current article provides a holistic summary of recent knowledge on adipokines and emphasizes their importance in association with IR, obesity, diabetes and MetS. Adipokines such as leptin, adiponectin, resistin and tumor necrosis factor-alpha (TNF-α) have been involved in the regulation of an array of metabolic functions and disease associated with it, e.g. appetite and energy balance of the body, suppression of atherosclerosis and liver fibrosis, obesity with type 2 diabetes (T2D) and IR. An important adipokine, Interleukin-6 (IL-6), also correlates positively with human obesity and IR and also the elevated level of IL-6 predicts development of T2D. All of these hormones have important correlation with energy homeostasis, glucose and lipid metabolism, cardiovascular function and immunity. All the possible connections have extended the biological emphasis of AT secreted adipokines as an investigator in the development of MetS, and are now no longer considered as only an energy storage site.
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Affiliation(s)
- Abhishek Gupta
- Department of Physiology, King George's Medical University, Lucknow, India
| | - Priyanka Gupta
- Department of Medicine, King George's Medical University, Lucknow, India
| | - Arun Kumar Singh
- Department of Physiology, King George's Medical University, Lucknow, India
| | - Vani Gupta
- Department of Physiology, King George's Medical University, Lucknow, India
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Allalou A, Peng J, Robinson GA, Marruganti C, D’Aiuto F, Butler G, Jury EC, Ciurtin C. Impact of puberty, sex determinants and chronic inflammation on cardiovascular risk in young people. Front Cardiovasc Med 2023; 10:1191119. [PMID: 37441710 PMCID: PMC10333528 DOI: 10.3389/fcvm.2023.1191119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 06/14/2023] [Indexed: 07/15/2023] Open
Abstract
Worrying trends of increased cardiovascular disease (CVD) risk in children, adolescents and young people in the Modern Era have channelled research and public health strategies to tackle this growing epidemic. However, there are still controversies related to the dynamic of the impact of sex, age and puberty on this risk and on cardiovascular health outcomes later in life. In this comprehensive review of current literature, we examine the relationship between puberty, sex determinants and various traditional CVD-risk factors, as well as subclinical atherosclerosis in young people in general population. In addition, we evaluate the role of chronic inflammation, sex hormone therapy and health-risk behaviours on augmenting traditional CVD-risk factors and health outcomes, ultimately aiming to determine whether tailored management strategies for this age group are justified.
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Affiliation(s)
- Amal Allalou
- University College London Medical School, University College London, London, United Kingdom
| | - Junjie Peng
- Centre for Adolescent Rheumatology Versus Arthritis, University College London, London, United Kingdom
- Centre for Rheumatology Research, Division of Medicine, University College London, London, United Kingdom
| | - George A. Robinson
- Centre for Adolescent Rheumatology Versus Arthritis, University College London, London, United Kingdom
- Centre for Rheumatology Research, Division of Medicine, University College London, London, United Kingdom
| | - Crystal Marruganti
- Eastman Dental Hospital, University College London Hospital, London, United Kingdom
| | - Francesco D’Aiuto
- Eastman Dental Hospital, University College London Hospital, London, United Kingdom
| | - Gary Butler
- Department of Paediatric Endocrinology, University College London Hospital, London, United Kingdom
- Institute of Child Health, University College London, London, United Kingdom
| | - Elizabeth C. Jury
- Centre for Rheumatology Research, Division of Medicine, University College London, London, United Kingdom
| | - Coziana Ciurtin
- Centre for Adolescent Rheumatology Versus Arthritis, University College London, London, United Kingdom
- Centre for Rheumatology Research, Division of Medicine, University College London, London, United Kingdom
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Chlorogenic Acid Restores Ovarian Functions in Mice with Letrozole-Induced Polycystic Ovarian Syndrome Via Modulation of Adiponectin Receptor. Biomedicines 2023; 11:biomedicines11030900. [PMID: 36979879 PMCID: PMC10045653 DOI: 10.3390/biomedicines11030900] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 02/25/2023] [Accepted: 03/03/2023] [Indexed: 03/17/2023] Open
Abstract
Around the world, polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic condition that typically affects 6–20% of females. Our study’s major goal was to examine how chlorogenic acid (CGA) affected mice with endocrine and metabolic problems brought on by letrozole-induced PCOS. Group I served as the control for 81 days; Group II was given Letrozole (LETZ) orally at a dose of 6 mg/kg bw for 21 days to induce PCOS; Group III was given LETZ (6 mg/kg) for 21 days, followed by treatment with CGA (50 mg/kg bw daily) for 60 days. The study indicated that LETZ-treated mice displayed symptoms of PCOS, such as dyslipidemia, hyperinsulinemia, elevated testosterone, increases in inflammatory markers and malonaldehyde, and a decline in antioxidants (Ar, lhr, fshr, and esr2) in the ovaries. These alterations were affected when the mice were given CGA and were associated with reduced levels of adiponectin. Adiponectin showed interactions with hub genes, namely MLX interacting protein like (MLXIPL), peroxisome proliferator-activated receptor gamma Coactivator 1- alpha (PPARGC1), peroxisome proliferator-activated receptor gamma (Pparg), and adiponectin receptor 1 (Adipor1). Lastly, the gene ontology of adiponectin revealed that adiponectin was highly involved in biological processes. The findings from our research suggest that adiponectin has direct impacts on metabolic and endocrine facets of PCOS.
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Rizzo M, Colletti A, Penson PE, Katsiki N, Mikhailidis DP, Toth PP, Gouni-Berthold I, Mancini J, Marais D, Moriarty P, Ruscica M, Sahebkar A, Vinereanu D, Cicero AFG, Banach M, Al-Khnifsawi M, Alnouri F, Amar F, Atanasov AG, Bajraktari G, Banach M, Gouni-Berthold I, Bhaskar S, Bielecka-Dąbrowa A, Bjelakovic B, Bruckert E, Bytyçi I, Cafferata A, Ceska R, Cicero AF, Chlebus K, Collet X, Daccord M, Descamps O, Djuric D, Durst R, Ezhov MV, Fras Z, Gaita D, Gouni-Berthold I, Hernandez AV, Jones SR, Jozwiak J, Kakauridze N, Kallel A, Katsiki N, Khera A, Kostner K, Kubilius R, Latkovskis G, John Mancini G, David Marais A, Martin SS, Martinez JA, Mazidi M, Mikhailidis DP, Mirrakhimov E, Miserez AR, Mitchenko O, Mitkovskaya NP, Moriarty PM, Mohammad Nabavi S, Nair D, Panagiotakos DB, Paragh G, Pella D, Penson PE, Petrulioniene Z, Pirro M, Postadzhiyan A, Puri R, Reda A, Reiner Ž, Radenkovic D, Rakowski M, Riadh J, Richter D, Rizzo M, Ruscica M, Sahebkar A, Serban MC, Shehab AM, Shek AB, Sirtori CR, Stefanutti C, Tomasik T, Toth PP, Viigimaa M, Valdivielso P, Vinereanu D, Vohnout B, von Haehling S, Vrablik M, Wong ND, Yeh HI, Zhisheng J, Zirlik A. Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP). Pharmacol Res 2023; 189:106679. [PMID: 36764041 DOI: 10.1016/j.phrs.2023.106679] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Revised: 01/25/2023] [Accepted: 01/26/2023] [Indexed: 02/11/2023]
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.
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Affiliation(s)
- Manfredi Rizzo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo, Via del Vespro 141, 90127 Palermo, Italy.
| | - Alessandro Colletti
- Department of Science and Drug Technology, University of Turin, Turin, Italy
| | - Peter E Penson
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK; Liverpool Centre for Cardiovascular Science, Liverpool, UK
| | - Niki Katsiki
- Department of Nutritional Sciences and Dietetics, International Hellenic University, Thessaloniki, Greece; School of Medicine, European University Cyprus, Nicosia, Cyprus
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry, Royal Free Campus, Medical School, University College London (UCL), London, UK
| | - Peter P Toth
- The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA; Preventive Cardiology, CGH Medical Center, Sterling, IL, USA
| | - Ioanna Gouni-Berthold
- Department of Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Germany
| | - John Mancini
- Department of Medicine, Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada
| | - David Marais
- Chemical Pathology Division of the Department of Pathology, University of Cape Town Health Science Faculty, Cape Town, South Africa
| | - Patrick Moriarty
- Division of Clinical Pharmacology, Division of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Massimiliano Ruscica
- Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Dragos Vinereanu
- Cardiology Department, University and Emergency Hospital, Bucharest, Romania, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania
| | - Arrigo Francesco Giuseppe Cicero
- Hypertension and Cardiovascular disease risk research center, Medical and Surgical Sciences Department, University of Bologna, Bologna, Italy; IRCCS Policlinico S. Orsola-Malpighi, Bologna, Italy
| | - Maciej Banach
- Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Poland; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland.
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Isolated vitamin D supplementation improves the adipokine profile of postmenopausal women: a randomized clinical trial. Menopause 2023; 30:56-62. [PMID: 36256949 DOI: 10.1097/gme.0000000000002084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The aim of the study is to evaluate the effect of vitamin D supplementation alone on the adipokine profile of postmenopausal women. METHODS In this randomized clinical trial, 160 women were randomized to 2 groups: oral supplementation with 1,000 IU cholecalciferol/d (vitamin D, n = 80) or placebo (PL, n = 80). Women with amenorrhea 12 months or more and aged 50 to 65 years were included. Women with established cardiovascular disease, insulin-dependent diabetes, renal failure, liver diseases, and previous use of menopausal hormone therapy and vitamin D were excluded. The intervention lasted 9 months and serum adiponectin, resistin, and adipsin levels were determined at the start and end of treatment. Intention to treat was adopted as the statistical method using a repeated measures design, followed by Wald's multiple comparison test adjusted for group × time interaction. RESULTS After 9 months, 25-hydroxyvitamin D concentrations increased from 15.0 ± 7.5 to 27.5 ± 10.4 ng/mL (+45.4%) in the vitamin D group and decreased from 16.9 ± 6. to 13.8 ± 6.0 ng/mL (-18.5%) in the PL group ( P < 0.001). In the vitamin D group, there was an increase in adiponectin (+18.6%) and a decrease in resistin (-32.4%, P < 0.05). At the end point, a difference was observed between the PL and vitamin D groups in mean adiponectin and resistin levels (11.5 ± 5.5 vs 18.5 ± 21.8 ng/mL, P = 0.047, and 16.5 ± 3.5 vs 11.7 ± 3.3 ng/mL, P = 0.027, respectively). There were no significant intervention effects on serum adipsin levels. CONCLUSIONS Daily supplementation with 1,000 IU of vitamin D alone was associated with an increase in adiponectin and a decrease in resistin, suggesting a beneficial effect on the adipokine profile of postmenopausal women with vitamin D deficiency.
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Fang WC, Chen HY, Chu SC, Wang PH, Lee CC, Wu IW, Sun CY, Hsu HJ, Chen CY, Chen YC, Wu VC, Pan HC. Serum Cystatin C Levels Could Predict Rapid Kidney Function Decline in A Community-Based Population. Biomedicines 2022; 10:2789. [PMID: 36359307 PMCID: PMC9687581 DOI: 10.3390/biomedicines10112789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 10/28/2022] [Accepted: 10/29/2022] [Indexed: 12/22/2023] Open
Abstract
BACKGROUND Several biomarkers have been correlated with the prevalence and severity of chronic kidney disease (CKD); however, the association between biomarkers and rapid kidney function decline (RKFD) is unknown. This study aimed to evaluate the predictive performance of biomarkers to determine who is likely to develop RKFD in a healthy population. METHODS A community-based cohort of 2608 people residing in northern Taiwan were enrolled, and their renal function was followed annually from January 2014 to December 2019. The outcomes of interest were RKFD, defined as a 15% decrease in the estimated glomerular filtration rate (eGFR) within the first 4 years, and a decrease in eGFR without improvement in the fifth year. Clinical variables and potential predictors of RKFD, namely adiponectin, leptin, tumor necrosis factor-alpha, and cystatin C, were measured and analyzed. RESULTS The incidence of RKFD was 17.0% (105/619). After matching for age and sex at a 1:1 ratio, a total of 200 subjects were included for analysis. The levels of cystatin C and total vitamin D were significantly negatively correlated with eGFR. eGFR was negatively correlated with the levels of cystatin C and total vitamin D. Among the biomarkers, cystatin C showed the best predictive performance for RKFD (area under the receiver operating characteristic curve: 0.789). Lower serum cystatin C was associated with a higher rate of RKFD in healthy subjects. A generalized additive model showed that 0.82 mg/L was an adequate cut-off value of cystatin C to predict RKFD. Multivariable logistic regression analysis further indicated that low cystatin C and eGFR were independent predictors of the possibility of RKFD. CONCLUSIONS Serum cystatin C level could predict the possibility of RKFD. We suggest that a low cystatin C level should be considered as a risk factor for RKFD in healthy subjects.
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Affiliation(s)
- Wei-Ching Fang
- Department of Family Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan;
| | - Hsing-Yu Chen
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
- Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Shao-Chi Chu
- Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan; (S.-C.C.); (P.-H.W.); (C.-C.L.); (I.-W.W.); (C.-Y.S.); (H.-J.H.); (C.-Y.C.)
| | - Po-Hsi Wang
- Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan; (S.-C.C.); (P.-H.W.); (C.-C.L.); (I.-W.W.); (C.-Y.S.); (H.-J.H.); (C.-Y.C.)
| | - Chin-Chan Lee
- Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan; (S.-C.C.); (P.-H.W.); (C.-C.L.); (I.-W.W.); (C.-Y.S.); (H.-J.H.); (C.-Y.C.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
- Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan
| | - I-Wen Wu
- Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan; (S.-C.C.); (P.-H.W.); (C.-C.L.); (I.-W.W.); (C.-Y.S.); (H.-J.H.); (C.-Y.C.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
- Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan
| | - Chiao-Yin Sun
- Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan; (S.-C.C.); (P.-H.W.); (C.-C.L.); (I.-W.W.); (C.-Y.S.); (H.-J.H.); (C.-Y.C.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
| | - Heng-Jung Hsu
- Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan; (S.-C.C.); (P.-H.W.); (C.-C.L.); (I.-W.W.); (C.-Y.S.); (H.-J.H.); (C.-Y.C.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
- Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan
| | - Chun-Yu Chen
- Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan; (S.-C.C.); (P.-H.W.); (C.-C.L.); (I.-W.W.); (C.-Y.S.); (H.-J.H.); (C.-Y.C.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
- Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan
| | - Yung-Chang Chen
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
- Division of Nephrology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Vin-Cent Wu
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan;
| | - Heng-Chih Pan
- Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan; (S.-C.C.); (P.-H.W.); (C.-C.L.); (I.-W.W.); (C.-Y.S.); (H.-J.H.); (C.-Y.C.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
- Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan
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Mendoza LC, Harreiter J, Desoye G, Simmons D, Adelantado JM, Kautzky-Willer A, Zawiejska A, Wender-Ozegowska E, Lapolla A, Dalfra MG, Bertolotto A, Devlieger R, Dunne F, Mathiesen ER, Damm P, Andersen LL, Jensen DM, Hill D, van Poppel MNM, Corcoy R. The Weak Relationship between Vitamin D Compounds and Glucose Homeostasis Measures in Pregnant Women with Obesity: An Exploratory Sub-Analysis of the DALI Study. Nutrients 2022; 14:nu14163256. [PMID: 36014761 PMCID: PMC9415540 DOI: 10.3390/nu14163256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 08/02/2022] [Accepted: 08/05/2022] [Indexed: 11/26/2022] Open
Abstract
Studies on the relationship between vitamin D (VitD) and glucose homeostasis usually consider either total VitD or 25OHD3 but not 25OHD2 and epimers. We aimed to evaluate the cross-sectional association of VitD compounds with glucose homeostasis measurements in pregnant women with overweight/obesity participating in the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus Prevention study. Methods: The analysis included 912 women. Inclusion criteria: <20 weeks gestation, body mass index ≥29 kg/m2 and information on exposure and outcome variables at baseline. Measurements: A 75 g OGTT at <20, 24−28 and 35−37 weeks gestation (except if previous diabetes diagnosis). Exposure variables: 25OHD2, 25OHD3 and C3-epimer. Outcome variables: fasting and post-challenge insulin sensitivity and secretion indices, corresponding disposition indices (DI), plasma glucose at fasting and 1 and 2 h, hyperglycemia in pregnancy (HiP). Statistics: Multivariate regression analyses with adjustment. Results: Baseline VitD sufficiency was 66.3%. Overall, VitD compounds did not show strong associations with any glucose homeostasis measures. 25OHD3 showed direct significant associations with: FPG at <20 and 24−28 weeks (standardized β coefficient (β) 0.124, p = 0.030 and 0.111, p = 0.026 respectively), 2 h plasma glucose at 24−28 weeks (β 0.120, p = 0.018), and insulin sensitivity (1/HOMA-IR, β 0.127, p = 0.027) at 35−37 weeks; it showed an inverse association with fasting DI (QUCKI*HOMA-β) at <20 and 24−28 weeks (β −0.124, p = 0.045 and β −0.148, p = 0.004 respectively). 25OHD2 showed direct associations with post-challenge insulin sensitivity (Matsuda, β 0.149, p = 0.048) at 24−28 weeks) and post-challenge DI (Matsuda*Stumvoll phase 1) at 24−28 and 35−37 weeks (β 0.168, p = 0.030, β 0.239, p = 0.006). No significant association with C3-epimer was observed at any time period. Conclusions: In these women with average baseline VitD in sufficiency range, VitD compounds did not show clear beneficial associations with glucose homeostasis measures.
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Affiliation(s)
- Lilian Cristina Mendoza
- Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain
- CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain
| | - Jürgen Harreiter
- Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Gender Medicine Unit, Medical University of Vienna, Waehringer Guertel 18–20, 1090 Vienna, Austria
| | - Gernot Desoye
- Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria
| | - David Simmons
- Macarthur Clinical School, School of Medicine, Western Sydney University, Campbelltown, NSE 2560, Australia
| | - Juan M. Adelantado
- Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain
| | - Alexandra Kautzky-Willer
- Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Gender Medicine Unit, Medical University of Vienna, Waehringer Guertel 18–20, 1090 Vienna, Austria
| | - Agnieszka Zawiejska
- Department of Reproduction, Poznan University of Medical Sciences, 60-525 Poznan, Poland
| | - Ewa Wender-Ozegowska
- Department of Reproduction, Poznan University of Medical Sciences, 60-525 Poznan, Poland
| | | | - Maria G. Dalfra
- Department of Medicine, University of Padova, 35128 Padova, Italy
| | - Alessandra Bertolotto
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Roland Devlieger
- Obstetrics and Gynecology, University Hospitals KU Leuven, 3000 Leuven, Belgium
| | - Fidelma Dunne
- College of Medicine, Nursing and Health Sciences, School of Medicine, National University of Ireland, H91 TK33 Galway, Ireland
| | - Elisabeth R. Mathiesen
- Center for Pregnant Women with Diabetes, Departments of Endocrinology and Obstetrics, Rigshospitalet, University of Copenhagen, DK-1165 Copenhagen, Denmark
| | - Peter Damm
- Center for Pregnant Women with Diabetes, Departments of Endocrinology and Obstetrics, Rigshospitalet, University of Copenhagen, DK-1165 Copenhagen, Denmark
| | - Lisse Lotte Andersen
- Department of Gynecology and Obstetrics, Odense University Hospital, 5000 Odense, Denmark
| | - Dorte Moller Jensen
- Department of Gynecology and Obstetrics, Odense University Hospital, 5000 Odense, Denmark
| | - David Hill
- Lawson Health Research Institute, St. Joseph Health Care, London, ON N6A 4V2, Canada
| | | | - Rosa Corcoy
- Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain
- CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain
- Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain
- Correspondence: ; Tel.: +34-93-556-56-61
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Ghanbari M, Lamuki MS, Habibi E, Sadeghimahalli F. Artemisia annua L. Extracts Improved Insulin Resistance via Changing Adiponectin, Leptin and Resistin Production in HFD/STZ Diabetic Mice. J Pharmacopuncture 2022; 25:130-137. [PMID: 35837139 PMCID: PMC9240412 DOI: 10.3831/kpi.2022.25.2.130] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 02/17/2022] [Accepted: 04/04/2022] [Indexed: 11/17/2022] Open
Abstract
Objectives Insulin resistance (IR) is major cause of type 2 diabetes (T2D), and adipokines (e.g., adiponectin, leptin, and resistin) play an important role in insulin sensitivity. Medicinal plants are frequently used for T2D treatment. This study investigates the effect of Artemisia annua L. (AA) extracts on adipokines in mice with high-fat-diet (HFD)/streptozotocin (STZ)-induced T2D. Methods We divided 60 mice into 12 groups (n = 5 per group) control, untreated T2D, treated T2D, and 9 other groups. T2D was induced in all groups, except controls, by 8 weeks of HFD and STZ injection. The treated T2D group was administered 250 mg/kg of metformin (MTF), while the nine other groups were treated with 100, 200, and 400 mg/kg of hot-water extract (HWE), cold-water extract (CWE), and alcoholic extract (ALE) of AA (daily oral gavage) along with 250 mg/kg of MTF for 4 weeks. The intraperitoneal glucose tolerance test (IPGTT) was performed, and the homeostasis model assessment of adiponectin (HOMA-AD) index and blood glucose and serum insulin, leptin, adiponectin, and resistin levels were measured. Results Similar to MTF, all three types of AA extracts (HWEs, CWEs, and ALEs) significantly (p < 0.0001) decreased the area under the curve (AUC) of glucose during the IPGTT, the HOMA-AD index, blood glucose levels, and serum insulin, leptin, and resistin levels and increased serum adiponectin levels in the MTF group compared to the T2D group (p < 0.0001). The HWEs affected adipokine release, while the CWEs and ALEs decreased leptin and resistin production. Conclusion Water and alcoholic AA extracts have an antihyperglycemic and antihyperinsulinemic effect on HFD/STZ diabetic mice. In addition, they decrease IR by reducing leptin and resistin production and increasing adiponectin secretion from adipocytes.
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Affiliation(s)
- Mahshid Ghanbari
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Manzandaran University of Medical Sciences, Sari, Iran
| | - Mohammad Shokrzadeh Lamuki
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Manzandaran University of Medical Sciences, Sari, Iran
- Pharmaceutical Science Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Emran Habibi
- Pharmaceutical Science Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran
- Department of Pharmacognosy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
| | - Forouzan Sadeghimahalli
- Pharmaceutical Science Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran
- Department of Physiology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
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Chen W, Yang H, Yan Q, Zhou X, Tan Z, Wang Z. Effects of maternal feed intake restriction on the blood parameters, fatty acid profile and lipogenetic genes expression of perirenal fat in offspring kids. Anim Reprod Sci 2022; 238:106955. [DOI: 10.1016/j.anireprosci.2022.106955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 02/16/2022] [Accepted: 02/20/2022] [Indexed: 11/17/2022]
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Turmeric extract alleviates endocrine-metabolic disturbances in letrozole-induced PCOS by increasing adiponectin circulation: A comparison with Metformin. Metabol Open 2022; 13:100160. [PMID: 35005596 PMCID: PMC8717583 DOI: 10.1016/j.metop.2021.100160] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Revised: 12/16/2021] [Accepted: 12/16/2021] [Indexed: 11/25/2022] Open
Abstract
One of the most common causes of female infertility is polycystic ovarian syndrome, which affects 6–21% of the population. Regrettably, the currently available treatments are mostly symptomatic and ineffective. As a result, safer options are needed now more than ever. In a letrozole PCOS albino mouse model, the current study compares the therapeutic advantages of Turmeric extract (Curcuma longa) to metformin. Adiponectin is a circulating protein generated by adipocytes that has been linked to metabolic diseases (MDs) in an inverse relationship. The effects of Turmeric Extract (Curcuma Longa) in contrast to Metformin, as well as the involvement of adiponectin in endocrine-metabolic abnormalities in experimentally induced PCOS mice model, were studied in this study. Letrozole (6 mg/kg) was administered orally (p.o) for 21 days to induce PCOS, followed by a dose of Turmeric Extract (Curcuma longa) (175 mg/kg and p.o) and Metformin (150 mg/kg) for 30 days, both with normal saline water (0.9%) as the carrier. The findings revealed that LET-treated mice displayed PCOS-like characteristics, such as higher LH levels, increased body weight growth, and ovarian morphology with numerous cysts, increase in fasting blood glucose, lipid profile, plasma lipid peroxidation (MDA) and IL-6, as well as a decrease in serum Progesterone, Estrogen, FSH, SOD and GSH levels in the ovary. These changes were linked to lower levels of circulating adiponectin and were reversed when treated Turmeric extract. By altering circulating androgen-adiponectin balance, the data implies that Turmeric extract alleviates endocrine-metabolic abnormalities and inflammation-related comorbidities associated with LET-induced PCOS.
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Karamali M, Gholizadeh M. The effects of coenzyme Q10 supplementation on metabolic profiles and parameters of mental health in women with polycystic ovary syndrome. Gynecol Endocrinol 2022; 38:45-49. [PMID: 34664527 DOI: 10.1080/09513590.2021.1991910] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
OBJECTIVE Evaluating the impact of coenzyme Q10 (CoQ10) supplementation on hormonal indices, mental health, and biomarkers of inflammatory responses and oxidative stress among female patients suffering from polycystic ovary syndrome (PCOS). METHODS The present double-blinded, placebo-controlled randomized clinical trial consisted of 55 PCOS women (aged 18-40 years old), who were randomized into groups receiving 100 mg/day of CoQ10 (28 cases) or placebo (27 cases) for 12 weeks. RESULTS The supplementation of CoQ10 decreased significantly the scores of Beck Depression Inventory (BDI) (p = .03) and Beck Anxiety Inventory (BAI) (p = .01) and high-sensitivity C-reactive protein (hs-CRP) level (p = .005) when comparing with the placebo group. Moreover, CoQ10 group exhibited a significant drop in total testosterone (p = .004), dehydroepiandrosterone sulfate (DHEAS) (p < .001), hirsutism (p = .002) and malondialdehyde (MDA) (p = .001) levels in the serum, and a significant rise in sex hormone-binding globulin (SHBG) (p < .001) and total antioxidant capacity (TAC) (p < .001) levels in the serum than the placebo group. CONCLUSIONS 12-week supplementation of CoQ10 to PCOS women showed beneficial impact on BDI, BAI, hs-CRP, total testosterone, DHEAS, hirsutism, SHBG, TAC and MDA levels.
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Affiliation(s)
- Maryam Karamali
- Department of Gynecology and Obstetrics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Masoumeh Gholizadeh
- Department of Gynecology and Obstetrics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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22
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Branda JIF, de Almeida-Pititto B, Bensenor I, Lotufo PA, Ferreira SRG. Low Birth Weight, β-Cell Function and Insulin Resistance in Adults: The Brazilian Longitudinal Study of Adult Health. Front Endocrinol (Lausanne) 2022; 13:842233. [PMID: 35360053 PMCID: PMC8964259 DOI: 10.3389/fendo.2022.842233] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 02/14/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Adverse intrauterine environment-reflected by low birth weight (LBW)-has been linked to insulin resistance and type 2 diabetes later in life. Whether β-cell function reduction and insulin resistance could be detected even in middle-aged adults without overt diabetes is less investigated. We examined the association of LBW with β-cell function and insulin sensitivity in non-diabetic middle-aged adults from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS This is a cross-sectional analysis of 2,634 ELSA-Brasil participants aged between 34 and 59 years, without diabetes. Participants were stratified according to LBW defined as <2.5 kg and their clinical data were compared. HOMA-IR, HOMA-β, HOMA-adiponectin, TyG index, QUICKI and TG/HDL were calculated and their association with LBW were tested using multiple linear regression including adjustments suggested by Directed Acyclic Graphs and propensity score matching was applied. RESULTS The sample (47.4 ± 6.3 years) was composed of 57.5% of women and 9% had LBW. Subjects with LBW and normal-weight reported similar BMI values at the age of 20 years and current BMI was slightly lower in the LBW group. In average, cardiometabolic risk profile and also indexes of β-cell function and insulin sensitivity were within normal ranges. In regression analysis, log-transformed HOMA-β-but not with the other indexes-was associated with LBW (p = 0.014) independent of sex, skin color, prematurity, and family history of diabetes. After applying propensity-score matching in a well-balanced sample, HOMA-AD and TG/HDL indexes were associated with LBW. CONCLUSION The association between LBW and insulin sensitivity markers may occur in healthy middle-aged adults before overt glucose metabolism disturbances. Our data are coherent with the detection of early life events consequent with insulin resistance markers that could contribute to the risk of glucose metabolism disturbances.
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Affiliation(s)
- Julia Ines F. Branda
- Department of Epidemiology, School of Public Health, University of São Paulo, São Paulo, Brazil
- Center of Clinical and Epidemiological Research at University of São Paulo, São Paulo, Brazil
| | - Bianca de Almeida-Pititto
- Center of Clinical and Epidemiological Research at University of São Paulo, São Paulo, Brazil
- Department of Preventive Medicine, Federal University of São Paulo, São Paulo, Brazil
| | - Isabela Bensenor
- Center of Clinical and Epidemiological Research at University of São Paulo, São Paulo, Brazil
- Department of Internal Medicine, Medical School, University of São Paulo, São Paulo, Brazil
| | - Paulo A. Lotufo
- Center of Clinical and Epidemiological Research at University of São Paulo, São Paulo, Brazil
- Department of Internal Medicine, Medical School, University of São Paulo, São Paulo, Brazil
| | - Sandra Roberta G. Ferreira
- Department of Epidemiology, School of Public Health, University of São Paulo, São Paulo, Brazil
- Center of Clinical and Epidemiological Research at University of São Paulo, São Paulo, Brazil
- *Correspondence: Sandra Roberta G. Ferreira,
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ul haq Shah MZ, Soni M, Shrivastava VK, Mir MA, Muzamil S. Gallic acid reverses ovarian disturbances in mice with letrozole-induced PCOS via modulating Adipo R1 expression. Toxicol Rep 2022; 9:1938-1949. [DOI: 10.1016/j.toxrep.2022.10.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/09/2022] [Accepted: 10/16/2022] [Indexed: 11/06/2022] Open
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Ahmed OAA, Hassan NA, Azhar AS, El-Mas MM, El-Bassossy HM. A Nano-Pharmaceutical Formula of Quercetin Protects from Cardiovascular Complications Associated with Metabolic Syndrome. Front Pharmacol 2021; 12:696981. [PMID: 34456723 PMCID: PMC8385560 DOI: 10.3389/fphar.2021.696981] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Accepted: 07/19/2021] [Indexed: 12/29/2022] Open
Abstract
Metabolic syndrome (MetS) is closely associated with the development of cardiovascular diseases. We recently developed a nano-preparation of the flavonoid quercetin (QU) in a self-nanoemulsifying drug delivery system (SNEDDS). The latter comprised a mixture composed of pumpkin seed oil, D-α-Tocopherol polyethylene glycol 1,000 succinate and polyethylene glycol. The QU SNEDDS preparations exhibited a considerably higher bioavailability compared with the standard quercetin suspension. Here, we investigated whether the quercetin loaded SNEDDS could offer better protection compared with the standard formulation against cardiovascular complications of MetS in rats. MetS was induced by high fructose, high salt and high fat diet for 12 weeks while the nano-preparation or the standard suspension of quercetin was orally administered for the last 6 weeks. Compared to little effect for the standard quercetin suspension (MQ), the treatment of MetS rats with the quercetin loaded SNEDDS (MNQ) virtually abolished the depressant effect of MetS on contractility index (control, 114 ± 4; MetS, 92 ± 3; MQ, 100 ± 2; MNQ, 114 ± 6 1/s) and rate of rise in left ventricular pressure (dP/dtmax) (control, 8,171 ± 274; MetS, 6,664 ± 135; MQ, 6,776 ± 108; MNQ, 7,498 ± 303 mmHg/s). Likewise, the prolongation by MetS of electrocardiographic markers of arrhythmogenesis (QTc, JT, and Tpeak-to-Tend intervals) and concomitant rises in dicrotic notch pressure were preferentially reversed by quercetin nano-preparation. On the other hand, the rises in the isovolumic relaxation constant (Tau, denotes diastolic dysfunction), blood pressure, pulse pressure, and difference between systolic and dicrotic pressure (SDP difference) were equally improved by the two preparations of quercetin. Additionally, no differences were noted in the ability of the two quercetin preparations in abrogating the elevated oxidative (MDA) and inflammatory (TNFα) markers in cardiac tissues of MetS rats. Histopathological, microscopical signs of necrosis, inflammatory cell infiltration, and vascular congestion in MetS hearts were more markedly inhibited by the nano-preparation, compared with the standard preparation of quercetin. In conclusion, the quercetin loaded SNEDDS is evidently more advantageous than the standard preparation of the drug in alleviating functional and histopathological manifestations of cardiac damage incited by MetS.
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Affiliation(s)
- Osama A A Ahmed
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.,Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Noura A Hassan
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
| | - Ahmad S Azhar
- Pediatric Cardiac Center of Excellence, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mahmoud M El-Mas
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.,Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait city, Kuwait
| | - Hany M El-Bassossy
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
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Zakhary CM, Rushdi H, Hamdan JA, Youssef KN, Khan A, Abdalla MA, Khan S. Protective Role of Vitamin D Therapy in Diabetes Mellitus Type II. Cureus 2021; 13:e17317. [PMID: 34567869 PMCID: PMC8451532 DOI: 10.7759/cureus.17317] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 08/20/2021] [Indexed: 01/15/2023] Open
Abstract
Diabetes Mellitus type II (DM II) is a worldwide disease with a rapidly growing parallel prevalence and adversities affecting multi-body systems. Hence, it is imperative to treat DM II effectively, maintaining glucose homeostasis to avoid complications such as diabetic nephropathy, peripheral neuropathy, and retinopathy. Vitamin D, among many benefits, has positive outcomes on hemoglobin A1c (HbA1c) control. It aids in insulin secretion and sensitivity. We systematically screened four databases for relevant information; PubMed, Medline, PMC, and Google scholar. Inclusion and exclusion criteria were applied, and quality appraisal was then done using certain checklist tools: Newcastle-Ottawa tool, AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklist, SANRA (Scale for the Assessment of Narrative Review Articles) checklist, and Cochrane bias assessment. Data were collected from 14 articles, of which eight are systematic reviews and meta-analysis, one is a narrative review, five are randomized controlled trials and three are general information about DM II and Vitamin D. In addition, this article evaluates the clinical significance of Vitamin D administration in DM II from a glucose homeostasis perspective, and complications such as nephropathy, neuropathy, and retinopathy. Vitamin D had a clinical positive impact on glucose level, particularly on hemoglobin A1c (HbA1c) reduction, alleviation of diabetic neuropathy and nephropathy symptoms, and hyperglycemia induced-oxidative stress on the retinal cells.
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Affiliation(s)
- Christine M Zakhary
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Hiam Rushdi
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Jaafar A Hamdan
- Medicine, American University of Antigua, St. John, ATG
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Kerolos N Youssef
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Aafreen Khan
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Mohammed A Abdalla
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Safeera Khan
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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Vajdi M, Mahmoudi-Nezhad M, Farhangi MA. An updated systematic review and dose-response meta-analysis of the randomized controlled trials on the effects of Alpha-Lipoic acid supplementation on inflammatory biomarkers. INT J VITAM NUTR RES 2021; 93:164-177. [PMID: 33827267 DOI: 10.1024/0300-9831/a000702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Data about the effects of alpha-lipoic acid (ALA) supplementation on inflammatory markers are inconsistent. This systematic review and dose-response meta-analysis of randomized controlled trials was performed to summarize the effects of ALA supplementation on inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in adults. A comprehensive literature search was conducted in the electronic databases of PubMed, Web of Science, ProQuest, Embase, and SCOPUS from inception to February 2020. Among all of the eligible studies, 20 articles were selected. The weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated to evaluate the pooled effect size. Between-study heterogeneity was evaluated using Cochran's Q test and I2. Subgroup analysis was done to evaluate the potential sources of heterogeneity. The dose-response relationship was evaluated using fractional polynomial modeling. Twenty eligible studies with a total sample size of 947 participants were included in the current meta-analysis. The findings of the meta-analysis showed that ALA supplementation significantly reduced CRP (WMD: -0.69 mg/L, 95% CI: -1.13, -0.26, P=0.002), IL-6 (WMD: -1.83 pg/ml, 95% CI: -2.90, -0.76, P=0.001), and TNF-α concentrations (WMD: -0.45 pg/ml, 95% CI: -0.85, -0.04, P=0.032). No evidence of departure from linearity was observed between dose and duration of the ALA supplementation on serum CRP, IL-6 and TNF-α concentration. In subgroup analysis, ALA dosage, baseline concentrations of the parameter, sample size, and gender were considered as possible sources of heterogeneity. In summary, ALA supplementation improves inflammatory markers without any evidence of non-linear association to dose or duration of the trial.
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Affiliation(s)
- Mahdi Vajdi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
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27
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Association of Gut Hormones and Microbiota with Vascular Dysfunction in Obesity. Nutrients 2021; 13:nu13020613. [PMID: 33668627 PMCID: PMC7918888 DOI: 10.3390/nu13020613] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 01/25/2021] [Accepted: 02/10/2021] [Indexed: 02/08/2023] Open
Abstract
In the past few decades, obesity has reached pandemic proportions. Obesity is among the main risk factors for cardiovascular diseases, since chronic fat accumulation leads to dysfunction in vascular endothelium and to a precocious arterial stiffness. So far, not all the mechanisms linking adipose tissue and vascular reactivity have been explained. Recently, novel findings reported interesting pathological link between endothelial dysfunction with gut hormones and gut microbiota and energy homeostasis. These findings suggest an active role of gut secretome in regulating the mediators of vascular function, such as nitric oxide (NO) and endothelin-1 (ET-1) that need to be further investigated. Moreover, a central role of brain has been suggested as a main player in the regulation of the different factors and hormones beyond these complex mechanisms. The aim of the present review is to discuss the state of the art in this field, by focusing on the processes leading to endothelial dysfunction mediated by obesity and metabolic diseases, such as insulin resistance. The role of perivascular adipose tissue (PVAT), gut hormones, gut microbiota dysbiosis, and the CNS function in controlling satiety have been considered. Further understanding the crosstalk between these complex mechanisms will allow us to better design novel strategies for the prevention of obesity and its complications.
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28
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Zardooz H, Sadeghimahalli F, Khodagholi F. Early postnatal stress impairs insulin secretion in response to psychological stress in adult rats. J Endocrinol Invest 2021; 44:277-286. [PMID: 32458408 DOI: 10.1007/s40618-020-01291-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 05/03/2020] [Indexed: 12/13/2022]
Abstract
PURPOSE Adversity in early life can induce metabolic defects in exposure to stress in adulthood. Therefore, the exploration of involving mechanisms can be helpful in the treatment of metabolic disorders. So, the present study was conducted in terms of exploring the effects of interaction between early postnatal stress and young adulthood psychological stress on insulin secretion and pancreatic GLUT-2 levels in male rats. METHODS Footshock as a model of early life stress (at 2 weeks of age) and psychological stress induced by communication box as a model of young adulthood stress (at 8-10 weeks of age) were induced in male Wistar rats for five consecutive days (2 times/day). Blood samples were drawn to measure glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell dysfunction (HOMA-B), before and after stress protocol in young adult rats. Corticosterone was measured on days 1 and 5 of stress induction. The day after the stress period, factors including glucose tolerance, TNF-alpha, isolated islets' insulin output and levels of pancreatic GLUT-2 protein via western blotting were determined. RESULTS The combination of early footshock exposure and psychological stress during adulthood did not affect plasma corticosterone, but increased plasma insulin, HOMA-IR, HOMA-B and TNF-alpha levels. Plasma TNF was not only increased by the combination of both stressors, but also after only E STR exposure. HOMA-IR was increased in both Psy STR and E + Psy-STR groups. Plasma glucose just increased in Psy STR group. The combination of these two life stressors further increased the in vitro insulin secretion from isolated islets in response to 16.7-mM glucose. The level of Glut2 was increased in Psy STR and decreased in both E STR and E + Psy STR groups. Finally, glucose tolerance was impaired and glucose-stimulated insulin secretion was increased in E + Psy STR group. CONCLUSIONS In conclusion, inducing stress in early life makes the organism more susceptible to metabolic defects in exposure to psychological stress later in life.
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Affiliation(s)
- H Zardooz
- Department of Physiology and Neurophysiology Research Center, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - F Sadeghimahalli
- Department of Physiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
- Diabetes Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
| | - F Khodagholi
- Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Olaniyi KS, Oniyide AA, Adeyanju OA, Ojulari LS, Omoaghe AO, Olaiya OE. Low dose spironolactone-mediated androgen-adiponectin modulation alleviates endocrine-metabolic disturbances in letrozole-induced PCOS. Toxicol Appl Pharmacol 2021; 411:115381. [PMID: 33359182 DOI: 10.1016/j.taap.2020.115381] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Revised: 12/09/2020] [Accepted: 12/17/2020] [Indexed: 12/11/2022]
Abstract
Polycystic ovarian syndrome (PCOS), is a multifactorial endocrine disorder in women of reproductive age. It usually associates with metabolic disorders (MDs), which aggravates the risk of infertility, cardiometabolic events and associated comorbidities in women with PCOS. Adiponectin, a circulating protein produced by adipocytes, which has been suggested to inversely correlate with MDs. Spironolactone, a non-selective mineralocorticoid receptor (MR) antagonist, has been in wide clinical use for several decades. Herein, we investigated the effects of low dose spironolactone (LDS) and the role of adiponectin in endocrine-metabolic disturbances in experimentally-induced PCOS rats. Eighteen female Wistar rats (160-180 g) were randomly allotted into 3 groups and treated with vehicle (p.o.), letrozole (LET; 1 mg/kg) and LET + LDS (0.25 mg/kg), once daily for 21 days, respectively. The results showed that LET-treated animals had features of PCOS, characterized by elevated plasma testosterone and prolactin, increased body weight gain and ovarian weight as well as disrupted ovarian cytoarchitecture and degenerated follicles. Additionally, elevated fasting blood glucose, 1 h-postload glucose and plasma insulin, impaired glucose tolerance, insulin resistance, reduced insulin sensitivity, increased plasma and ovarian lipid profile, plasma lipid peroxidation, TNF-α, IL-6 and decreased plasma glutathione peroxidase and glutathione content were observed. These alterations were associated with decreased circulating adiponectin and were reversed when treated with LDS. The present results suggest that LDS ameliorates endocrine-metabolic disturbances and inflammation-related comorbidities associated with LET-induced PCOS by modulating circulating androgen-adiponectin status.
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Affiliation(s)
- Kehinde S Olaniyi
- Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria.
| | - Adesola A Oniyide
- Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria
| | - Oluwaseun A Adeyanju
- Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria.
| | - Lekan S Ojulari
- Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria
| | - Adams O Omoaghe
- Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria
| | - Oluranti E Olaiya
- Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria
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Ferns GA, Shahini Shams Abadi M, Arjmand MH. The potential association between metabolic syndrome and risk of post-surgical adhesion. Arch Physiol Biochem 2020; 129:649-654. [PMID: 33290664 DOI: 10.1080/13813455.2020.1856882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Abstract
Metabolic syndrome (MetS) is defined by the clustering of several associated with a group of disorders that include: obesity, dyslipidemia, hypertension, and insulin resistance. The incidence of MetS is increasing globally around the world. Indeed the rates of different types of surgery in older or younger patients with Mets are increasing and they are exposed to a wide range of operations including abdominal, pelvic, urologic, or any invasive procedures. Post-surgical adhesion is a common problem and is a challenge for the surgeon. Despite many studies on its pathogenesis, there remain many un-answered questions about it, for example why certain tissues and patients are more at higher risk of post-surgical adhesions. Many studies have suggested that MetS is associated with up-regulating molecular mechanisms leading to chronic inflammation and hypercoagulability. In this review, we discuss some of the molecular mechanisms by MetS may enhance post-surgical adhesion, and particularly regarding those involved in coagulation and inflammation.
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Affiliation(s)
- Gordon A Ferns
- Brighton & Sussex Medical School, Division of Medical Education, Brighton, UK
| | - Milad Shahini Shams Abadi
- Department of Microbiology and Immunology, Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
- Cancer Research Center, Shahrekord university of Medical Sciences, Shahrekord, Iran
| | - Mohammad-Hassan Arjmand
- Cancer Research Center, Shahrekord university of Medical Sciences, Shahrekord, Iran
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
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Hagag AA, El Frargy MS, Abd El-Latif AE. Study of Cord Blood Erythropoietin, Leptin and Adiponectin Levels in Neonates with Hypoxic Ischemic Encephalopathy. Endocr Metab Immune Disord Drug Targets 2020; 20:213-220. [PMID: 31345155 DOI: 10.2174/1871530319666190725110619] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2019] [Revised: 04/20/2019] [Accepted: 05/21/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Hypoxic ischemic encephalopathy (HIE) is a serious condition which results in neonatal morbidity and mortality. Early prediction of HIE especially in the first six hours of birth leads to early treatment with better prognosis. AIM The aim of this study was to compare the concentrations of leptin, adiponectin, and erythropoietin between normal neonates and those with HIE for the possible use of these markers for assessment of the degree of HIE and as markers for early prediction of HIE. PATIENTS AND METHODS This study was carried out on 50 appropriate for gestational age (AGA) neonates with HIE born in Tanta University Hospital during the period from June 2016 to March 2018 (Group I). This study also included 50 appropriate for gestational age (AGA) normal neonates not suffering from any complications and matched with group I in age and sex as a control group (Group II). For all neonates in both groups, the following were done: Complete prenatal, natal, and postnatal history, assessment of APGAR score at 5 and 10 minutes, complete clinical examination with special account on clinical evidence of encephalopathy including hypotonia, abnormal oculomotor or pupillary movements, weak or absent suckling, apnea, hyperpnea, or seizures, measurement of cord blood gases and measurement of serum erythropoietin, leptin and adiponectin levels by ELISA immediately after birth. RESULTS There were no significant differences between Group I and Group II regarding gestational age, male to female ratio, mode of delivery, and weight while there were significant differences regarding Apgar score at 1 and 5 minutes with significantly lower Apgar score at 1 and 5 minutes in group I compared with Group II. There were significantly lower cord blood PH and adiponectin level and significantly higher cord blood Leptin and erythropoietin in group I compared with group II. There were significant differences between cord blood adiponectin, leptin, erythropoietin, and PH in different degrees of HIE with significantly lower cord blood adiponectin and PH and significantly higher cord blood leptin and erythropoietin in severe degree of hypoxia compared with moderate degree and in moderate degree compared with mild degree of hypoxia. There was a significant positive correlation between cord blood erythropoietin and leptin and a significant negative correlation between cord blood erythropoietin and both adiponectin and PH in studied neonates with hypoxia. ROC curve showed that EPO had the best sensitivity and specificity followed by leptin then adiponectin while the PH had the least sensitivity and specificity as early predictors of hypoxic neonates. CONCLUSION AND RECOMMENDATIONS Neonates with HIE had lower cord blood PH and adiponectin levels and higher leptin and erythropoietin levels than normal healthy neonates at birth and during the early postnatal period. The significant differences between cord blood erythropoietin, leptin, and adiponectin between neonates with hypoxia compared with normal neonates may arouse our attention about the use of these markers in the cord blood as early predictors of neonatal HIE which can lead early treatment and subsequently better prognosis.
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Affiliation(s)
- Adel A Hagag
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta, Gharbia, Egypt
| | - Mohamed S El Frargy
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta, Gharbia, Egypt
| | - Amal E Abd El-Latif
- Clinical Pathology Department, Faculty of Medicine, Tanta University, Tanta, Gharbia, Egypt
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Vitamin D and Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD): An Update. Nutrients 2020; 12:nu12113302. [PMID: 33126575 PMCID: PMC7693133 DOI: 10.3390/nu12113302] [Citation(s) in RCA: 111] [Impact Index Per Article: 22.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 10/26/2020] [Accepted: 10/27/2020] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the first cause of chronic liver disease worldwide; it ranges from simple steatosis to steatohepatitis (NASH) and, potentially, cirrhosis and hepatocarcinoma. NAFLD is also an independent risk factor for type 2 diabetes, cardiovascular diseases, and mortality. As it is largely associated with insulin resistance and related disorders, NAFLD has been recently re-named as Metabolic dysfunction-Associated Fatty Liver Disease (MAFLD). At present, there are no approved pharmacological treatments for this condition. Vitamin D is a molecule with extensive anti-fibrotic, anti-inflammatory, and insulin-sensitizing properties, which have been proven also in hepatic cells and is involved in immune-metabolic pathways within the gut–adipose tissue–liver axis. Epidemiological data support a relationship hypovitaminosis D and the presence of NAFLD and steatohepatitis (NASH); however, results from vitamin D supplementation trials on liver outcomes are controversial. This narrative review provides an overview of the latest evidence on pathophysiological pathways connecting vitamin D to NAFLD, with emphasis on the effects of vitamin D treatment in MAFLD by a nonsystematic literature review of PubMed published clinical trials. This article conforms to the Scale for Assessment of Narrative Review Articles (SANRA) guidelines. Evidence so far available supports the hypothesis of potential benefits of vitamin D supplementation in selected populations of NAFLD patients, as those with shorter disease duration and mild to moderate liver damage.
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Kim GR, Choi DW, Nam CM, Jang SI, Park EC. Synergistic association of high-sensitivity C-reactive protein and body mass index with insulin resistance in non-diabetic adults. Sci Rep 2020; 10:18417. [PMID: 33116232 PMCID: PMC7595183 DOI: 10.1038/s41598-020-75390-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Accepted: 09/22/2020] [Indexed: 11/15/2022] Open
Abstract
Epidemiological evidence has indicated that inflammatory markers and obesity are strongly correlated with insulin resistance (IR). However, there is a paucity of studies assessing the complex interaction between elevated hs-CRP and body mass index (BMI), particularly among Asians. This study investigated the additive interaction between hs-CRP and BMI on IR, using cross-sectional data from the 7th Korea National Health and Nutrition Examination Survey (2016–2018). A total of 5706 men and 6707 women aged 20 years or older were evaluated, and a multiple logistic regression analysis was used to assess the association of serum hs-CRP and BMI with IR, as measured by the triglyceride-glucose index (TyG index). Sex-specific median values were used to dichotomise the continuous TyG index variable into insulin-sensitive and IR categories. Biological interaction was evaluated using the Relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI). The joint effects of high hs-CRP and overweight/obesity on IR were greater than would be expected from the effects of the individual exposures alone. Relative to those with low hs-CRP and BMI < 23, having both exposures was related to increased IR with an adjusted OR of 2.97 (95% CI 2.50–3.52) in men and 3.08 (95% CI 2.67–3.56) in women with significant additive interactions. These findings demonstrate that IR prevention strategies that reduce both systematic inflammation and BMI may exceed the expected benefits based on targeting these risk factors separately.
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Affiliation(s)
- Gyu Ri Kim
- Department of Preventive Medicine, College of Medicine, Yonsei University, Seoul, Korea.,Institute of Health Services Research, Yonsei University, Seoul, Korea
| | - Dong-Woo Choi
- Department of Public Health, Graduate School, Yonsei University, Seoul, Korea.,Institute of Health Services Research, Yonsei University, Seoul, Korea
| | - Chung Mo Nam
- Department of Preventive Medicine, College of Medicine, Yonsei University, Seoul, Korea.,Department of Biostatistics, College of Medicine, Yonsei University, Seoul, Korea
| | - Sung-In Jang
- Department of Preventive Medicine, College of Medicine, Yonsei University, Seoul, Korea.,Institute of Health Services Research, Yonsei University, Seoul, Korea
| | - Eun-Cheol Park
- Department of Preventive Medicine, College of Medicine, Yonsei University, Seoul, Korea. .,Institute of Health Services Research, Yonsei University, Seoul, Korea.
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Gunturiz Albarracín ML, Forero Torres AY. Adiponectin and Leptin Adipocytokines in Metabolic Syndrome: What Is Its Importance? DUBAI DIABETES AND ENDOCRINOLOGY JOURNAL 2020. [DOI: 10.1159/000510521] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
The global obesity epidemic has motivated a large number of investigations related to adipose tissue. Within the advances in this area, a variety of factors secreted by adipose tissue and with regulatory activity on caloric intake, energy expenditure, reproduction, locomotor activity, glycidic and lipid metabolism, immune response, and bone physiology have been described. Among these adipocyte hormones, collectively called “adipokines” or “adipocytokines,” leptin (LEP) and adiponectin are addressed in this review. The regulation of adipocytokines is altered in diseases such as obesity, atherosclerosis, type 2 diabetes mellitus, and metabolic syndrome (MS) due to the increase in the mass of white adipose tissue. LEP and adiponectin have a broad spectrum of functions in regulating metabolism and are an important link between obesity and MS. Because these adipocytokines have opposite effects on subclinical inflammation and insulin resistance, it has been suggested that the combined use of these 2 adipocytokines may work as a better biomarker in the diagnosis of MS than using them individually. In this review, we address the characteristics and main functions of adipocytokines derived from adipose tissue such as adiponectin and LEP, which in the Colombian context could give good guidance for the management of MS, especially in populations of children and adolescents.
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Zarezadeh M, Khorshidi M, Emami M, Janmohammadi P, Kord-Varkaneh H, Mousavi SM, Mohammed SH, Saedisomeolia A, Alizadeh S. Melatonin supplementation and pro-inflammatory mediators: a systematic review and meta-analysis of clinical trials. Eur J Nutr 2020; 59:1803-1813. [PMID: 31679041 DOI: 10.1007/s00394-019-02123-0] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 10/21/2019] [Indexed: 12/25/2022]
Abstract
BACKGROUND Inflammatory processes are involved in chronic diseases. It has been suggested that melatonin reduces inflammation by its radical scavenging properties; however, the results of the previous studies are inconclusive. The objective of the present meta-analysis is to determine the direction and magnitude of melatonin supplementation effect on inflammatory biomarkers. METHODS Databases including PubMed, Scopus, Cochran Library, Embase, and Google Scholar were searched up to April 2019. Meta-analysis was performed using random-effect model. Subgroup analysis, sensitivity analysis, and meta-regression were also carried out. RESULTS Thirteen eligible studies with 22 datasets with total sample size of 749 participants were included in the meta-analysis. Melatonin supplementation significantly decreased TNF-α and IL-6 levels [(WMD = - 2.24 pg/ml; 95% CI - 3.45, - 1.03; P < 0.001; I2 = 96.7%, Pheterogeneity < 0.001) and (WMD = - 30.25 pg/ml; 95% CI - 41.45, - 19.06; P < 0.001, I2 = 99.0%; Pheterogeneity < 0.001)], respectively. The effect of melatonin on CRP levels was marginal (WMD = - 0.45 mg/L; 95% CI - 0.94, 0.03; P = 0.06; I2 = 96.6%, Pheterogeneity < 0.001). CONCLUSION The results of the present meta-analysis support that melatonin supplementation could be effective on ameliorating of inflammatory mediators.
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Affiliation(s)
- Meysam Zarezadeh
- Department of Clinical Nutrition, Student Research Committee, Nutrition Research Center, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Masoud Khorshidi
- Student Research Committee, Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
- Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children Health, Mofid Children's Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Emami
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Parisa Janmohammadi
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamed Kord-Varkaneh
- Student Research Committee, Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Mohammad Mousavi
- Department of Community Nutrition, Students' Scientific Research Center (SSRC), School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Shimels Hussien Mohammed
- Department of Community Nutrition, Students' Scientific Research Center (SSRC), School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmad Saedisomeolia
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
- School of Medicine, Western Sydney University, Sydney, NSW, 2560, Australia.
| | - Shahab Alizadeh
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
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Brand C, Gaya ACA, Dias AF, Agostinis-Sobrinho C, Farinha JB, Boeno FP, Mota J, Reischak de Oliveira A, Gaya AR. Relationship between insulin resistance and adipocytokines: the mediator role of adiposity in children. Ann Hum Biol 2020; 47:244-249. [PMID: 32279531 DOI: 10.1080/03014460.2020.1740320] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Background: Leptin and adiponectin interact with each other in the modulation of obesity and insulin resistance (IR) and it is also important to consider the role of cardiorespiratory and muscular fitness in these relationships.Aim: To analyse the relationship between IR with adipocytokines in children, and to test the mediation effect of %BF (percentage of body fat) in the association of IR with leptin, adiponectin, and L/A ratio.Subjects and methods: This cross-sectional study comprised a sample of 150 schoolchildren, aged 6-11 years, from school in Porto Alegre, Brazil. The following variables were evaluated: cardiorespiratory fitness (CRF), muscular fitness (MF), percentage of body fat (%BF), and biochemical variables (leptin, adiponectin, glucose, and insulin).Results: IR was associated with leptin and L/A ratio, after adjustments for age, sex, sexual maturation, and CRF. When adjusted for age, sex, sexual maturation, and MF, an association was found between IR with leptin and L/A ratio. Moreover, %BF was a mediator in the association between IR and leptin, as well as IR and L/A ratio, explaining 54% and 57% of these associations, respectively.Conclusion: Leptin and L/A ratio are positively associated with IR after adjustments. Also, %BF is a mediator in the associations between IR and leptin and L/A ratio.
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Affiliation(s)
- Caroline Brand
- School of Physical Education, Physiotherapy and Dance, Post-Graduation Program in Human Movement Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Adroaldo Cezar Araujo Gaya
- School of Physical Education, Physiotherapy and Dance, Post-Graduation Program in Human Movement Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Arieli Fernandes Dias
- School of Physical Education, Physiotherapy and Dance, Post-Graduation Program in Human Movement Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | | | - Juliano Boufleur Farinha
- School of Physical Education, Physiotherapy and Dance, Post-Graduation Program in Human Movement Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Francesco Pinto Boeno
- School of Physical Education, Physiotherapy and Dance, Post-Graduation Program in Human Movement Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Jorge Mota
- Faculty of Sport, University of Porto, Porto, Portugal
| | - Alvaro Reischak de Oliveira
- School of Physical Education, Physiotherapy and Dance, Post-Graduation Program in Human Movement Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Anelise Reis Gaya
- School of Physical Education, Physiotherapy and Dance, Post-Graduation Program in Human Movement Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
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EMS-effect of Exercises with Music on Fatness and Biomarkers of Obese Elderly Women. MEDICINA-LITHUANIA 2020; 56:medicina56040158. [PMID: 32244777 PMCID: PMC7231244 DOI: 10.3390/medicina56040158] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 03/27/2020] [Accepted: 03/30/2020] [Indexed: 02/06/2023]
Abstract
Background and objectives: Electromyostimulation (EMS) has been shown to improve body composition, but what biomarkers it affects has not been investigated. The purpose of this study was to compare the EMS-effect of exercises with music on fatness and biomarker levels in obese elderly. Materials and Methods: Twenty-five women were randomly classified into a control group (CON) and EMS group (EMSG). EMS suits used in this study enabled the simultaneous activation of eight pairs with selectable intensities. Program sessions of EMS were combined with exercises of listening to music three times a week for eight weeks. Although both groups received the same program, CON did not receive electrical stimuli. Results: Compared with CON, a significant effect of the EMS intervention concerning decreased fatness, as well as an increased skeletal muscle mass and basal metabolic rate, were evident. Tumor necrosis factor-a, C-reactive protein, resistin, and carcinoembryonic antigen of biomarkers were significantly different in the groups by time interaction. Similarly, the positive changes caused by EMS were represented in lipoprotein-cholesterols. Conclusions: The results indicate that a significant effect due to the EMS intervention was found concerning body composition and biomarkers in obese elderly women.
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Tobore TO. Towards a comprehensive theory of obesity and a healthy diet: The causal role of oxidative stress in food addiction and obesity. Behav Brain Res 2020; 384:112560. [DOI: 10.1016/j.bbr.2020.112560] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 02/14/2020] [Accepted: 02/14/2020] [Indexed: 02/06/2023]
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Hezaveh ZS, Sikaroudi MK, Vafa M, Clayton ZS, Soltani S. Effect of egg consumption on inflammatory markers: a systematic review and meta-analysis of randomized controlled clinical trials. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2019; 99:6663-6670. [PMID: 31259415 PMCID: PMC7189602 DOI: 10.1002/jsfa.9903] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 05/24/2019] [Accepted: 06/03/2019] [Indexed: 05/12/2023]
Abstract
There is little evidence about whether eggs affect inflammation. The aim of this meta-analysis was to explore the effects of egg consumption on inflammation. A systematic search of online databases (Institute for Scientific Information (ISI), Scopus, Ovid, PubMed, Cochrane) was used to gather clinical trials that assessed the effect of egg consumption on circulating inflammatory biomarkers. Using a random-effects model, pooled weighted mean differences (WMD) and corresponding standard deviations (SD) were calculated. Of the 21 eligible studies found, nine trials were eligible for analysis. Eight trials assessed high-sensitivity C-reactive protein (hs-CRP), four trials assessed interleukin-6 (IL-6), and five trials assessed tumor necrosis factor-alpha (TNF-α). Egg consumption did not affect hs-CRP (WMD 0.24 mg/L; 95% CI: -0.43, 0.90; I2 = 53.8; P = 0.48), IL-6 (WMD 0.20 pg/mL; 95% CI: -0.71, 1.11; I2 = 69.3; P = 0.50), and TNF-α (WMD: -0.38 pg/mL; 95% CI: -0.87, 0.10; I2 = 0.00; P = 0.12) relative to controls. Overall, this meta-analysis revealed that egg consumption had no significant effect on serum biomarkers of inflammation in adults. © 2019 Society of Chemical Industry.
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Affiliation(s)
- Zohreh Sajadi Hezaveh
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | | | - Mohammadreza Vafa
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | | | - Sepideh Soltani
- Department of Nutrition, Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Yazd Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Correspondence to: S Soltani, Yazd Cardiovascular Research Center, Shahid Sadoughi University ofMedical Sciences, Yazd, Iran.
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Impact of vitamin D supplementation on cardio-metabolic status and androgen profile in women with polycystic ovary syndrome: placebo-controlled clinical trial. MIDDLE EAST FERTILITY SOCIETY JOURNAL 2019. [DOI: 10.1186/s43043-019-0005-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Abstract
Background
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of reproductive, endocrine, and metabolic functions. Vitamin D has an influence on metabolic and reproductive functions. This study was designed to explore the levels of free 25 hydroxycholecalciferol [25(OH)-D] in PCOS patients. We also aimed to clarify the impact of vitamin D supplementation on cardio-metabolic status, androgen profile, and clinical features of PCOS.
Results
Our results revealed significant lower levels of serum 25(OH)-D in PCOS women compared with healthy controls. Even more importantly, our results reported that 25(OH)-D levels were negatively correlated with cardio-metabolic risk factors, androgenic profile, and clinical features of PCOS. Stepwise multiple linear regression analysis revealed that carotid intima-media thickness (CIMT), fasting serum insulin (FSI), and fasting plasma glucose (FPG) were the main predictors of 25(OH)-D levels among other clinical and laboratory biomarkers. Considering the impact of VD supplementation in the PCOS group, there were significant improvements of cardio-metabolic risks, PCOS phenotype, and androgenic profile. Even more important, these results are associated with increasing 25(OH)-D serum levels after VD supplementations. Logistic regression analysis observed that androstenedione, FSI, and hirsutism score were independent predictors of response to VD supplementation.
Conclusion
The supplementation of VD for 12 weeks improved the cardio-metabolic and androgenic profiles of PCOS. Furthermore, VD supplementation could be a promising treatment of PCOS and its associated morbidity in PCOS-deficient women.
Trial registration
NCT04117750
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Yang TH, Chiu CY, Lu TJ, Liu SH, Chiang MT. The Anti-Obesity Effect of Polysaccharide-Rich Red Algae ( Gelidium amansii) Hot-Water Extracts in High-Fat Diet-Induced Obese Hamsters. Mar Drugs 2019; 17:md17090532. [PMID: 31540318 PMCID: PMC6780553 DOI: 10.3390/md17090532] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 09/12/2019] [Accepted: 09/12/2019] [Indexed: 12/17/2022] Open
Abstract
This study investigated the anti-obesity effect of a polysaccharide-rich red algae Gelidium amansii hot-water extract (GHE) in high-fat (HF) diet-induced obese hamsters. GHE contained 68.54% water-soluble indigestible carbohydrate polymers. Hamsters were fed with a HF diet for 5 weeks to induce obesity, and then randomly divided into: HF group, HF with 3% guar gum diet group, HF with 3% GHE diet group, and HF with orlistat (200 mg/kg diet) group for 9 weeks. The increased weights of body, liver, and adipose in the HF group were significantly reversed by GHE supplementation. Lower plasma leptin, tumor necrosis factor-α, and interleukin-6 levels were observed in the GHE+HF group compared to the HF group. GHE also increased the lipolysis rate and decreased the lipoprotein lipase activity in adipose tissues. GHE induced an increase in the phosphorylation of AMP-activated protein kinase (AMPK) and the protein expressions of peroxisome proliferator-activated receptor alpha (PPARα) and uncoupling protein (UCP)-2 in the livers. The decreased triglyceride and total cholesterol in the plasma and liver were also observed in obese hamsters fed a diet with GHE. These results suggest that GHE exerts a down-regulation effect on hepatic lipid metabolism through AMPK phosphorylation and up-regulation of PPARα and UCP-2 in HF-induced obese hamsters.
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Affiliation(s)
- Tsung-Han Yang
- Department of Food Science, National Taiwan Ocean University, Keelung 20224, Taiwan.
| | - Chen-Yuan Chiu
- Medical and Pharmaceutical Industry Technology and Development Center, New Taipei City 24886, Taiwan.
| | - Ting-Jang Lu
- Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan.
| | - Shing-Hwa Liu
- Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
- Department of Pediatrics, College of Medicine, National Taiwan University Hospital, Taipei 10051, Taiwan.
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan.
| | - Meng-Tsan Chiang
- Department of Food Science, National Taiwan Ocean University, Keelung 20224, Taiwan.
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Jee YS. The effect of high-impulse- electromyostimulation on adipokine profiles, body composition and strength: A pilot study. ISOKINET EXERC SCI 2019. [DOI: 10.3233/ies-183201] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Yong-Seok Jee
- Research Institute of Sports and Industry Science, Hanseo University, #46 Hanseo 1-Ro, Haemi-myeon, Seosan 31962, Korea
- Department of Physical Activity Design, Hanseo University, #46 Hanseo 1-Ro, Haemi-myeon, Seosan 31962, Seosan, Korea
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Hossain M, Nahar B, Haque MA, Mondal D, Mahfuz M, Naila NN, Gazi MA, Hasan MM, Haque NMS, Haque R, Arndt MB, Walson JL, Ahmed T. Serum Adipokines, Growth Factors, and Cytokines Are Independently Associated with Stunting in Bangladeshi Children. Nutrients 2019; 11:nu11081827. [PMID: 31394828 PMCID: PMC6723106 DOI: 10.3390/nu11081827] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Revised: 08/06/2019] [Accepted: 08/06/2019] [Indexed: 02/07/2023] Open
Abstract
Growth in young children is controlled through the release of several hormonal signals, which are affected by diet, infection, and other exposures. Stunting is clearly a growth disorder, yet limited evidence exists documenting the association of different growth biomarkers with child stunting. This study explored the association between different growth biomarkers and stunting in Bangladeshi children. A quasi-experimental study was conducted among 50 stunted (length-for-age Z-score (LAZ) < -2 SD) and 50 control (LAZ ≥ -2 SD) children, aged 12-18 months, residing in a Bangladeshi slum. The enrolled stunted children received an intervention package, which included food supplementation for three months, psychosocial stimulation for six months, and routine clinical care on community nutrition center at the study field site. The controls received routine clinical care only. All children were clinically screened over the study period. Length, weight, fasting blood and fecal biomarkers were measured. All biomarkers levels were similar in both groups except for oxyntomodulin at enrolment. Leptin (adjusted odds ratio, AOR: 4.0, p < 0.01), leptin-adiponectin ratio (AOR 5.07 × 108, p < 0.01), insulin-like growth factor-1 (IGF-1) (AOR 1.02, p < 0.05), and gamma interferon (IFN-γ) (AOR 0.92, p < 0.05) levels were independently associated with stunting at enrolment. Serum leptin, leptin-adiponectin ratio, interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha (TNF-α), and fecal alpha-1-antitrypsin (AAT) levels increased significantly (p < 0.001), while IFN-γ levels significantly decreased among stunted children after six months of intervention. Leptin, leptin-adiponectin ratio, IGF-1, and IFN-γ are independently associated with stunting in Bangladeshi children. This trial was registered at clinicaltrials.gov as NCT02839148.
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Affiliation(s)
- Muttaquina Hossain
- Nutrition and Clinical Services Division, icddr,b, Dhaka 1212, Bangladesh.
| | - Baitun Nahar
- Nutrition and Clinical Services Division, icddr,b, Dhaka 1212, Bangladesh
| | - Md Ahshanul Haque
- Nutrition and Clinical Services Division, icddr,b, Dhaka 1212, Bangladesh
| | - Dinesh Mondal
- Nutrition and Clinical Services Division, icddr,b, Dhaka 1212, Bangladesh
| | - Mustafa Mahfuz
- Nutrition and Clinical Services Division, icddr,b, Dhaka 1212, Bangladesh
| | - Nurun Nahar Naila
- Nutrition and Clinical Services Division, icddr,b, Dhaka 1212, Bangladesh
| | - Md Amran Gazi
- Nutrition and Clinical Services Division, icddr,b, Dhaka 1212, Bangladesh
| | - Md Mehedi Hasan
- Nutrition and Clinical Services Division, icddr,b, Dhaka 1212, Bangladesh
| | | | - Rashidul Haque
- Enteric and Respiratory Infections, icddr,b, Dhaka 1212, Bangladesh
| | - Michael B Arndt
- PATH, Seattle, WA 98109, USA
- Department of Global Health, University of Washington, Seattle, WA 98109, USA
| | - Judd L Walson
- Department of Global Health, University of Washington, Seattle, WA 98109, USA
- Department of Pediatrics, University of Washington, Seattle, WA 98109, USA
- Childhood Acute Illness and Nutrition Network, Nairobi 00200, Kenya
- Departments of Medicine, University of Washington, Seattle, WA 98109, USA
- Department of Epidemiology, University of Washington, Seattle, WA 98109, USA
| | - Tahmeed Ahmed
- Nutrition and Clinical Services Division, icddr,b, Dhaka 1212, Bangladesh
- Department of Global Health, University of Washington, Seattle, WA 98109, USA
- James P. Grant School of Public Health, BRAC University, Dhaka 1212, Bangladesh
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Kaufman JM, Lapauw B, Mahmoud A, T'Sjoen G, Huhtaniemi IT. Aging and the Male Reproductive System. Endocr Rev 2019; 40:906-972. [PMID: 30888401 DOI: 10.1210/er.2018-00178] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Accepted: 12/27/2018] [Indexed: 12/21/2022]
Abstract
This narrative review presents an overview of current knowledge on fertility and reproductive hormone changes in aging men, the factors driving and modulating these changes, their clinical consequences, and the benefits and risks of testosterone (T) therapy. Aging is accompanied by moderate decline of gamete quality and fertility. Population mean levels show a mild total T decline, an SHBG increase, a steeper free T decline, and a moderate LH increase with important contribution of comorbidities (e.g., obesity) to these changes. Sexual symptoms and lower hematocrit are associated with low T and are partly responsive to T therapy. The relationship of serum T with body composition and metabolic health is bidirectional; limited beneficial effects of T therapy on body composition have only marginal effects on metabolic health and physical function. Skeletal changes are associated primarily with estradiol and SHBG. Cognitive decline is not consistently linked to low T and is not improved by T therapy. Although limited evidence links moderate androgen decline with depressive symptoms, T therapy has small beneficial effects on mood, depressive symptoms, and vitality in elderly patients with low T. Suboptimal T (and/or DHT) has been associated with increased risk of stroke, but not of ischemic heart disease, whereas an association with mortality probably reflects that low T is a marker of poor health. Globally, neither severity of clinical consequences attributable to low T nor the nature and magnitude of beneficial treatment effects justify the concept of some broadly applied "T replacement therapy" in older men with low T. Moreover, long-term safety of T therapy is not established.
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Affiliation(s)
- Jean-Marc Kaufman
- Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
| | - Bruno Lapauw
- Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
| | - Ahmed Mahmoud
- Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
| | - Guy T'Sjoen
- Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
| | - Ilpo Tapani Huhtaniemi
- Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.,Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland
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Salonia A, Rastrelli G, Hackett G, Seminara SB, Huhtaniemi IT, Rey RA, Hellstrom WJG, Palmert MR, Corona G, Dohle GR, Khera M, Chan YM, Maggi M. Paediatric and adult-onset male hypogonadism. Nat Rev Dis Primers 2019; 5:38. [PMID: 31147553 PMCID: PMC6944317 DOI: 10.1038/s41572-019-0087-y] [Citation(s) in RCA: 169] [Impact Index Per Article: 28.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The hypothalamic-pituitary-gonadal axis is of relevance in many processes related to the development, maturation and ageing of the male. Through this axis, a cascade of coordinated activities is carried out leading to sustained testicular endocrine function, with gonadal testosterone production, as well as exocrine function, with spermatogenesis. Conditions impairing the hypothalamic-pituitary-gonadal axis during paediatric or pubertal life may result in delayed puberty. Late-onset hypogonadism is a clinical condition in the ageing male combining low concentrations of circulating testosterone and specific symptoms associated with impaired hormone production. Testosterone therapy for congenital forms of hypogonadism must be lifelong, whereas testosterone treatment of late-onset hypogonadism remains a matter of debate because of unclear indications for replacement, uncertain efficacy and potential risks. This Primer focuses on a reappraisal of the physiological role of testosterone, with emphasis on the critical interpretation of the hypogonadal conditions throughout the lifespan of the male individual, with the exception of hypogonadal states resulting from congenital disorders of sex development.
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Affiliation(s)
- Andrea Salonia
- Division of Experimental Oncology, Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
- Università Vita-Salute San Raffaele, Milan, Italy.
| | - Giulia Rastrelli
- Sexual Medicine and Andrology Unit Department of Experimental Clinical and Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy
| | - Geoffrey Hackett
- Department of Urology, University of Bedfordshire, Bedfordshire, UK
| | - Stephanie B Seminara
- Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Ilpo T Huhtaniemi
- Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, London, UK
- Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland
| | - Rodolfo A Rey
- Centro de Investigaciones Endocrinológicas 'Dr César Bergadá' (CEDIE), CONICET - FEI - División de Endocrinología, Hospital de Niños R. Gutiérrez, Buenos Aires, Argentina
| | - Wayne J G Hellstrom
- Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA
| | - Mark R Palmert
- Division of Endocrinology, The Hospital for Sick Children, Toronto, Ontario, Canada
- Departments of Paediatrics and Physiology, University of Toronto, Toronto, Ontario, Canada
| | - Giovanni Corona
- Sexual Medicine and Andrology Unit Department of Experimental Clinical and Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy
- Endocrinology Unit, Medical Department, Azienda Usl Bologna Maggiore-Bellaria Hospital, Bologna, Italy
| | - Gert R Dohle
- Department of Urology, Erasmus University Medical Centre, Rotterdam, Netherlands
| | - Mohit Khera
- Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA
| | - Yee-Ming Chan
- Division of Endocrinology, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Mario Maggi
- Sexual Medicine and Andrology Unit Department of Experimental Clinical and Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy
- Istituto Nazionale Biostrutture e Biosistemi (INBB), Rome, Italy
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Navarro-Triviño F, Arias-Santiago S, Gilaberte-Calzada Y. Vitamin D and the Skin: A Review for Dermatologists. ACTAS DERMO-SIFILIOGRAFICAS 2019. [DOI: 10.1016/j.adengl.2019.04.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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Navarro-Triviño FJ, Arias-Santiago S, Gilaberte-Calzada Y. Vitamin D and the Skin: A Review for Dermatologists. ACTAS DERMO-SIFILIOGRAFICAS 2019; 110:262-272. [PMID: 30857638 DOI: 10.1016/j.ad.2018.08.006] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Revised: 07/28/2018] [Accepted: 08/02/2018] [Indexed: 02/07/2023] Open
Abstract
In recent years, the growing interest in the role played by vitamin D in skin disease has given rise to the publication of many studies of the relationship between this vitamin and certain skin conditions. As dermatologists, we need to understand, among other aspects, how vitamin D is synthesized and the main sources in humans, as well as plasma levels and the factors that can modify them. Of particular interest are the latest discoveries about the role of vitamin D in skin diseases such as lupus erythematosus, ichthyosis, atopic dermatitis, hidradenitis suppurativa, acne, alopecia areata, androgenetic alopecia, melanoma, and nonmelanoma skin cancer. Also of interest is the importance of vitamin D as adjuvant therapy in patients on long-term treatment with corticosteroids. In this review, we provide an overview of the most important and most recent information regarding the relationship between vitamin D and skin disease and discuss the importance of assessing individual vitamin D status and correcting deficiencies.
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Affiliation(s)
- F J Navarro-Triviño
- Unidad de Dermatología Médico-Quirúrgica y Venereología, Hospital Comarcal Alcalá la Real, Jaén, España.
| | - S Arias-Santiago
- Unidad de Gestión Clínica de Dermatología y Venereología, Hospital Universitario Virgen de las Nieves, Granada, España
| | - Y Gilaberte-Calzada
- Servicio de Dermatología, Hospital Universitario Miguel Servet, IIS Aragón, Zaragoza, España
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Grammatiki M, Karras S, Kotsa K. The role of vitamin D in the pathogenesis and treatment of diabetes mellitus: a narrative review. Hormones (Athens) 2019; 18:37-48. [PMID: 30255482 DOI: 10.1007/s42000-018-0063-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Accepted: 08/09/2018] [Indexed: 12/21/2022]
Abstract
Diabetes mellitus, a metabolic disorder associated with chronic complications, is traditionally classified into two main subtypes. Type 1 diabetes mellitus (T1DM) results from gradual pancreatic islet β cell autoimmune destruction, extending over months or years. Type 2 diabetes mellitus (T2DM) is a heterogeneous disorder, with both insulin resistance and impairment in insulin secretion contributing to its pathogenesis. Vitamin D is a fat-soluble vitamin with an established role in calcium metabolism. Recently, several studies have provided evidence suggesting a role for it in various non-skeletal metabolic conditions, including both types of diabetes mellitus. Preclinical studies of vitamin D action on insulin secretion, insulin action, inflammatory processes, and immune regulation, along with evidence of an increase of hypovitaminosis D worldwide, have prompted several epidemiological, observational, and supplementation clinical studies investigating a potential biological interaction between hypovitaminosis D and diabetes. This narrative review aims to summarize current knowledge on the effect of vitamin D on T1DM and T2DM pathogenesis, prevention, and treatment, as well as on micro- and macrovascular complications of the disease. Furthermore, on the basis of current existing evidence, we aim to highlight areas for potential future research.
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Affiliation(s)
- Maria Grammatiki
- Department of Endocrinology and Metabolism-Diabetes Center, 1st Department of Internal Medicine, AHEPA University Hospital, S. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Spiros Karras
- Department of Endocrinology and Metabolism-Diabetes Center, 1st Department of Internal Medicine, AHEPA University Hospital, S. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Kalliopi Kotsa
- Department of Endocrinology and Metabolism-Diabetes Center, 1st Department of Internal Medicine, AHEPA University Hospital, S. Kiriakidi 1, 54636, Thessaloniki, Greece.
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Zhou X, Xu C, Zou Z, Shen X, Xie T, Zhang R, Liao L, Dong J. aThe characteristics of glucose metabolism in the sulfonylurea receptor 1 knockout rat model. Mol Med 2019; 25:2. [PMID: 30616503 PMCID: PMC6322298 DOI: 10.1186/s10020-018-0067-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Accepted: 12/11/2018] [Indexed: 12/26/2022] Open
Abstract
Background Sulfonylurea receptor 1 (SUR1) is primarily responsible for glucose regulation in normal conditions. Here, we sought to investigate the glucose metabolism characteristics of SUR1−/− rats. Methods The TALEN technique was used to construct a SUR1 gene deficiency rat model. Rats were grouped by SUR1 gene knockout or not and sex difference. Body weight; glucose metabolism indicators, including IPGTT, IPITT, glycogen contents and so on; and other molecule changes were examined. Results Insulin secretion was significantly inhibited by knocking out the SUR1 gene. SUR1−/− rats showed lower body weights compared to wild-type rats, and even SUR1−/− males weighed less than wild-type females. Upon SUR1 gene knockout, the rats showed a peculiar plasma glucose profile. During IPGTT, plasma glucose levels were significantly elevated in SUR1−/− rats at 15 min, which could be explained by SUR1 mainly working in the first phase of insulin secretion. Moreover, SUR1−/− male rats showed obviously impaired glucose tolerance than before and a better insulin sensitivity in the 12th week compared with females, which might be related with excess androgen secretion in adulthood. Increased glycogen content and GLUT4 expression and the inactivation of GSK3 were also observed in SUR1−/− rats, which suggested an enhancement of insulin sensitivity. Conclusions These results reconfirm the role of SUR1 in systemic glucose metabolism. More importantly, our SUR1−/− rat model might be applied in other fields, such as for exploring other hypoglycaemic functions of sulfonylureas. Electronic supplementary material The online version of this article (10.1186/s10020-018-0067-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Xiaojun Zhou
- Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250014, People's Republic of China
| | - Chunmei Xu
- Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250014, People's Republic of China
| | - Zhiwei Zou
- Department of Endocrinology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, 250012, People's Republic of China
| | - Xue Shen
- Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Tianyue Xie
- Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Rui Zhang
- Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250014, People's Republic of China
| | - Lin Liao
- Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250014, People's Republic of China.
| | - Jianjun Dong
- Department of Endocrinology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, 250012, People's Republic of China.
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Benites-Zapata VA, Toro-Huamanchumo CJ, Urrunaga-Pastor D, Guarnizo-Poma M, Lazaro-Alcantara H, Paico-Palacios S, Pantoja-Torres B, Ranilla-Seguin VDC. High waist-to-hip ratio levels are associated with insulin resistance markers in normal-weight women. Diabetes Metab Syndr 2019; 13:636-642. [PMID: 30641781 DOI: 10.1016/j.dsx.2018.11.043] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Accepted: 11/13/2018] [Indexed: 02/07/2023]
Abstract
AIM To assess the association between high waist-to-hip ratio (WHR) levels and insulin resistance (IR) or hyperinsulinemia after oral glucose tolerance test (OGTT) in a sample of normal-weight women. METHODS We conducted an analytical cross-sectional study in euthyroid non-diabetic women, who attended the outpatient service of a private clinic in Lima-Peru from 2012 to 2016. Participants were divided in two groups according to the presence or absence of high WHR levels, IR or hyperinsulinemia after OGTT. We considered WHR values > 0.85 as high levels. IR was defined as a Homeostasis Model Assessment (HOMA-IR) value > 2.39 and hyperinsulinemia after OGTT as a serum insulin value ≥ 80μU/mL after 120 min of 75-g glucose intake. We elaborated crude and adjusted Poisson generalized linear models to evaluate the association between high WHR levels and IR or hyperinsulinemia after OGTT and reported the prevalence ratio (PR) with their respective 95% confidence intervals (95%CI). RESULTS We analyzed the data of 248 euthyroid, non-diabetic and normal-weight women. The prevalence of high WHR levels was 68.9% (n = 171) while the prevalence of IR and hyperinsulinemia after OGTT was 25% (n = 62) and 15.3% (n = 38), respectively. WHR values were positively correlated with HOMA-IR (r = 0.307; p < 0.001) and serum insulin after OGTT (r = 0.260; p < 0.001). In the adjusted model, high WHR levels were associated with both IR (aPR = 2.63; 95%CI: 1.39-5.01) and hyperinsulinemia after OGTT (aPR = 2.35; 95%CI: 1.03-5.38). CONCLUSION High WHR levels were associated with both IR markers used in our study, appearing to be a useful anthropometric indicator to assess IR in euthyroid normal-weight women without type 2 diabetes mellitus.
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Affiliation(s)
| | - Carlos J Toro-Huamanchumo
- Universidad San Ignacio de Loyola, Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Lima, Peru.
| | - Diego Urrunaga-Pastor
- Universidad San Ignacio de Loyola, Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Lima, Peru.
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