DOCSLIB.ORG

Serum Levels of the Adipokine Progranulin Depend on Renal Function

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Serum Levels of the Adipokine Progranulin Depend on Renal Function Pathophysiology/Complications ORIGINAL ARTICLE Serum Levels of the Adipokine Progranulin Depend on Renal Function 1,2 4 JUDIT RICHTER, MS JURGEN€ KRATZSCH, PHD acrogranin, and granulin-epithelin precur- 1 5 DENISE FOCKE, MD JOACHIM BEIGE, MD 1,2 6 sor) has most recently been introduced as THOMAS EBERT, MD MATTHIAS ANDERS, MD 3 6 a novel adipokine inducing insulin resis- PETER KOVACS, PHD INGOLF BAST, MD 1 1 tance. Thus, Matsubara et al. (5) identified ANETTE BACHMANN, MD MATTHIAS BLUHER€ , MD 1,2 1 progranulin as an adipokine induced by ULRIKE LÖSSNER, BS MICHAEL STUMVOLL, MD 1,2 1,2 a SUSAN KRALISCH, PHD, MSC MATHIAS FASSHAUER, MD TNF- and dexamethasone by differential proteome analysis in cellular models of in- sulin resistance. Furthermore, the authors OBJECTIVEdProgranulin has recently been introduced as a novel adipokine inducing insulin convincingly demonstrated that progranulin resistance and obesity. In the current study, we investigated renal elimination, as well as asso- knockout mice are resistant to high-fat ciation of the adipokine with markers of the metabolic syndrome. diet–induced insulin resistance, adipocyte hypertrophy, and obesity (5). Mechanisti- d fi RESEARCH DESIGN AND METHODS Progranulin serum levels were quanti ed by cally, progranulin deficiency blocked eleva- enzyme-linked immunosorbent assay and correlated to anthropometric and biochemical param- eters of renal function and glucose and lipid metabolism, as well as inflammation, in 532 patients tion of IL-6 in blood and adipose tissue with stages 1–5 of chronic kidney disease (CKD). induced by high-fat feeding (5). Most inter- estingly, progranulin-induced insulin resis- RESULTSdMedian serum progranulin levels adjusted for age, sex, and BMI were significantly tance was suppressed by neutralizing IL-6 different between CKD stages with highest values detectable in stage 5 (stage 1, 58.3 mg/L; stage in vivo (5). In addition, the authors demon- m m m m 2, 63.0 g/L; stage 3, 65.4 g/L; stage 4, 68.8 g/L; and stage 5, 90.6 g/L). Furthermore, CKD strate that progranulin levels in blood and stage was the strongest independent predictor of circulating progranulin in our cohort. In ad- adipose tissue were markedly increased in dition, high-sensitivity interleukin-6 and adiponectin remained significantly and independently correlated with the adipokine. obese mice (5). In agreement with these findings, Youn et al. (6) revealed that serum CONCLUSIONSdWe demonstrate that progranulin serum levels increase with deteriorating concentrations of progranulin were also ele- renal function. These findings are in accordance with the hypothesis that renal clearance is a vated in obese patients, as well as patients major elimination route for circulating progranulin. Furthermore, the adipokine is positively and with type 2 diabetes, compared with indi- fl independently associated with markers of in ammation and adiponectin. viduals with normal glucose tolerance. Furthermore, a study by the same group Diabetes Care 36:410–414, 2013 demonstrated higher progranulin levels in insulin resistant compared with insulin- he incidence of obesity and related genic peptides in the hypothalamus (1). sensitive individuals with morbid obesity Tdisorders including insulin resis- When body weight increases, leptin resis- (7). Interestingly, a recent study by Tönjes tance, type 2 diabetes, dyslipidemia, tance occurs leading to diminished central, et al. (8) suggests that progranulin is asso- and hypertension has increased dramati- appetite-suppressive effects of this adipo- ciated with impaired glucose tolerance cally in recent decades. Hyperplasia and kine despite higher levels in obesity (1). rather than impaired fasting glucose. In ad- hypertrophy of adipocytes during weight Adiponectin, another adipokine, has potent dition, serum levels of progranulin de- fl fl gain in uence the secretion pattern of insulin-sensitizing and anti-in ammatory creased in overweight subjects during a adipose tissue, and altered secretion of effects (2). In contrast, tumor necrosis factor long-term diet intervention indicating a adipocyte-derived proteins, so-called (TNF)-a and interleukin (IL)-6 are proin- fl mechanistic link between body weight adipokines, contributes to the increased ammatory adipokines that correlate with and circulating levels of this adipokine (9). risk for metabolic and cardiovascular increasing body weight and induce insulin Most recently, an elegant study showed diseases in obesity. Thus, the adipokine resistance (3,4). that a combination of four urinary proteins leptin strongly suppresses appetite by in- Progranulin (also referred to as pro- including progranulin could predict early ducing anorexigenic and inhibiting orexi- epithelin, PC-cell–derived growth factor, renal damage in type 1 diabetes, suggesting ccccccccccccccccccccccccccccccccccccccccccccccccc that the adipokine might be involved in From the 1Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany; the the pathogenesis of complications of the 2Leipzig University Medical Center, IFB Adiposity Diseases, Leipzig, Germany; the 3Interdisciplinary Center disease (10). Moreover, serum progranulin for Clinical Research, University of Leipzig, Leipzig, Germany; the 4Institute of Laboratory Medicine, was higher in patients with nonalcoholic 5 University of Leipzig, Leipzig, Germany; the Division of Nephrology and KfH Renal Unit, Hospital St. fatty liver disease compared with control Georg, Leipzig, Germany; and the 6Outpatient Nephrology Care Unit, Leipzig, Germany. Corresponding author: Mathias Fasshauer, [email protected]. subjects (11). With these studies taken into Received 1 February 2012 and accepted 25 July 2012. consideration, progranulin appears as a DOI: 10.2337/dc12-0220 novel adipokine upregulated in obesity A slide set summarizing this article is available online. and inducing insulin resistance. J.R. and D.F. contributed equally to this study. © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly However, no data have been published cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/ thus far concerning progranulin in relation to licenses/by-nc-nd/3.0/ for details. renal function in contrast to other adipokines 410 DIABETES CARE, VOLUME 36, FEBRUARY 2013 care.diabetesjournals.org Richter and Associates including leptin and adiponectin (12,13). diseases, acute generalized inflammation, progranulin serum levels increased with If renal function influenced levels of circu- acute infectious disease, and history of deteriorating renal function, with highest lating progranulin, we would anticipate 1) drug abuse. The study was approved by levels seen in stage 5 of CKD (Table 1). accumulation of the adipokine with dete- the local ethics committee. In contrast,a significant difference in riorating renal function and 2) correlation progranulin concentrations could not be of progranulin with estimated glomerular Assays demonstrated depending on sex (female filtration rate (eGFR) independent of met- Blood samples were taken after an over- 69.9 mg/L [interquartile range 25.4]; male abolic and inflammatory markers. To test night fast. In hemodialysis patients, blood 71.8 mg/L [31.5]), type 2 diabetes (type 2 our hypothesis, we quantified progranu- was obtained just before hemodialysis diabetic patients 71.6 mg/L [29.8]; nondia- lin serum concentrations in 532 patients started. Progranulin (R&D Systems, Min- betic subjects 70.4 mg/L [27.0]), or current with chronic kidney disease (CKD) stages neapolis, MN), high-sensitivity IL-6 smoking (smoker mg/L 75.4 [35.7]; non- 1–5 and correlated this adipokine to clin- (hsIL-6) (R&D Systems, Minneapolis, smoker mg/L 70.5 [26.9]). ical and biochemical markers of renal MN), leptin (Mediagnost, Reutlingen, function, glucose, and lipid metabolism, Germany), and adiponectin (Mediagnost) Univariate correlations as well as inflammation. were determined with enzyme-linked im- Serum progranulin concentrations in all munosorbent assays according to the man- individuals positively and significantly ufacturers’ instructions. Serum creatinine; correlated with WHR, WHtR, serum cre- RESEARCH DESIGN AND fasting glucose; fasting insulin; triglycer- atinine, triglycerides, hsCRP, hsIL-6, and METHODSdFor this cross-sectional ides; total, HDL, and LDL cholesterol, and adiponectin (Table 2). In addition, pro- study, 532 patients (men, n = 305; high-sensitivity C-reactive protein (hsCRP) granulin was negatively and significantly women, n = 227) were recruited by the were measured in a certified laboratory by associated with diastolic blood pressure Department of Endocrinology and Ne- standard methods. (DBP), eGFR, fasting glucose, total choles- phrology, University of Leipzig, as well terol, HDL cholesterol, and LDL cholesterol as from three outpatient Nephrology Statistical analysis (Table 2). Furthermore, in a subset of 351 Care units (KfH Renal Unit, Division of SPSS software, version 18.0 (IBM, Armonk, individuals, circulating progranulin was Nephrology, Hospital St. Georg, and out- NY), was used for all statistical analyses. not significantly associated with fat mass, patient Nephrology Care units, Leipzig). Overall group differences for continuous body fat percentage, lean body mass, or All patients were classified into CKD parameters were assessed by Kruskal- basic metabolic rate assessed by bioelectri- stages 1–5 according to the National Kid- Wallis test followed
Load more

Recommended publications
  • Effect of High Glucose Levels on White Adipose Cells and Adipokines—Fuel for the Fire
    Review Effect of High Glucose Levels on White Adipose Cells and Adipokines—Fuel for the Fire Alexander Sorisky Chronic Disease Program, Ottawa Hospital Research Institute, and Departments of Medicine and of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, ON K1H 8L6, Canada; [email protected]; Tel.: +1-613-737-8899 Academic Editor: Christa Buechler Received: 17 March 201; Accepted: 26 April 2017; Published: 29 April 2017 Abstract: White adipocytes release adipokines that influence metabolic and vascular health. Hypertrophic obesity is associated with adipose tissue malfunctioning, leading to inflammation and insulin resistance. When pancreatic islet β cells can no longer compensate, the blood glucose concentration rises (hyperglycemia), resulting in type 2 diabetes. Hyperglycaemia may further aggravate adipose cell dysfunction in ~90% of patients with type 2 diabetes who are obese or overweight. This review will focus on the effects of high glucose levels on human adipose cells and the regulation of adipokines. Keywords: adipocytes; hyperglycaemia; adipokines 1. Introduction The mature white adipocyte is distinguished morphologically by the large lipid droplet that occupies most of its interior space. Here, excess energy can be safely stored as an endogenous fuel until metabolic demand requires it to be released. Insulin levels are low in the fasting state, and rise in the post-prandial period. Counter-regulatory hormones, such as epinephrine and glucagon, follow the opposite pattern. Together, they regulate the enzymatic machinery within the adipocyte to achieve the storage of calories as triglyceride following meals, and the release of energy in the form of free fatty acids during fasting or exercise. These well-orchestrated processes maintain metabolic health [1].
    [Show full text]
  • Adipokine Levels and Perilipin Gene Polymorphisms in Obese Turkish Adolescents with Non-Alcoholic Fatty Liver Disease
    65 Erciyes Med J 2018; 40(2): 65-9 • DOI: 10.5152/etd.2018.0010 Adipokine Levels and Perilipin Gene Polymorphisms in Obese Turkish Adolescents with Non-Alcoholic Fatty Liver Disease 1 2 3 4 5 6 ORIGINAL Yavuz Tokgöz , Cahit Barış Erdur , Soheil Akbari , Tuncay Kume , Oya Sayin , Semiha Terlemez , ARTICLE Esra Erdal3, Nur Arslan2 ABSTRACT Objective: The aim of the present study was to evaluate the relationship between adipokines and perilipin (PLIN) polymor- phisms with non-alcoholic fatty liver disease (NAFLD). Cite this article as: Tokgöz Methods: Obese Turkish adolescents were assessed in the study. The patients were divided into two groups: obese (NAFLD Y, Erdur CB, Akbari S, and non-NAFLD) and non-obese. Serum leptin, adiponectin, resistin, and ghrelin levels and PLIN gene analysis (PLIN 1, 4, and Kume T, Sayın O, Terlemez 6) were studied in all patients and healthy control group. Data obtained were compared with those of healthy control group. S, et al. Adipokine Levels and Perilipin Gene Results: Overall, 83 obese adolescents with NAFLD, 123 obese adolescents with normal liver, and 102 healthy non-obese Polymorphisms in Obese adolescents as the control group were evaluated. No significant difference was observed in terms of serum adipokine (leptin, Turkish Adolescents with Non-Alcoholic Fatty Liver adiponectin, resistin, and ghrelin) levels in patients with NAFLD and non-NAFLD obese adolescents. The incidence of major Disease Erciyes Med J alleles of PLIN 6 genotype in obese adolescents without NAFLD was slightly higher than that in the control group (p=0.06). 2018; 40(2): 65-9.
    [Show full text]
  • Wake Forest Comprehensive Cancer Center Annual Report 2014
    2014 CANCER PROGRAM ANNUAL REPORT WITH 2013 STATISTICS TABLE OF CONTENTS 1 MESSAGE FROM THE DIRECTOR 2 CANCER REGISTRY 4 CANCER COMMITTEE MEMBERS/ CANCER REGISTRY STAFF 5 CANCER ACTIVITIES 23 CANCER DATA 29 PUBLISHED ABSTRACTS Giant Cell Carcinoma Courtesy of Dr. A. Julian Garvin, Department of Pathology 2014 1 CANCER PROGRAM ANNUAL REPORT ANNUAL PROGRAM CANCER Comprehensive Cancer Center AT WAKE FOREST BAPTIST MEDICAL CENTER “ We are extremely proud of the achievements of our Comprehensive Cancer Center as we strive to deliver the best care possible to our patients, their families and caregivers.” – Boris Pasche, MD, PhD, FACP Director, Comprehensive Cancer Center The Comprehensive Cancer Center The Cancer Center recognizes the existing floors, which house all at Wake Forest Baptist Medical the importance of building cross- outpatient oncology services as well Center was founded in the early departmental and transdisciplinary clinical trial staff. This new building 1960s and became a National Cancer team approaches to advance the provides an exceptional environment Institute-designated cancer center science and treatment of cancer. for patients, family and caregiver in 1974, shortly after the National Teams have been developed in cancer experience. Cutting-edge research Cancer Act was placed into law. genomics, tumor microenvironment, and precision medicine is available The Cancer Center received an NCI nanotechnology, imaging, novel to all patients, who have access to “comprehensive” designation in 1990. anticancer drugs, novel anticancer approximately 200 clinical trials. It is one of the longest-standing NCI devices, cancer survivorship, tobacco The Cancer Center was founded with centers, and we are proud to be a part control and cancer health disparities.
    [Show full text]
  • A Neutrophil Activation Signature Predicts Critical Illness and Mortality in COVID-19
    medRxiv preprint doi: https://doi.org/10.1101/2020.09.01.20183897; this version posted September 2, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. A neutrophil activation signature predicts critical illness and mortality in COVID-19 Matthew L. Meizlish,1* Alexander B. Pine,2* Jason D. Bishai,3* George Goshua,2 Emily R. Nadelmann,4 Michael Simonov,5 C-Hong Chang,3 Hanming Zhang,3 Marcus Shallow,3 Parveen Bahel,6 Kent Owusu,7 Yu Yamamoto,5 Tanima Arora,5 Deepak S. Atri,8 Amisha Patel,2 Rana Gbyli,2 Jennifer Kwan,3 Christine H. Won,9 Charles Dela Cruz,9 Christina Price,10 Jonathan Koff,9 Brett A. King,11 Henry M. Rinder,6 F. Perry Wilson,5 John Hwa,3 Stephanie Halene,2 William Damsky,11 David van Dijk,3 Alfred I. Lee2†, Hyung J. Chun3,12 † Affiliations: 1Yale School of Medicine, New Haven, CT 06510, USA 2Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA 3Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA 4Clinical and Translational Research Accelerator, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA 5Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06510, USA 6Yale New Haven Health System, New Haven, CT 06510, USA 9Section of Section of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA 10Section of Immunology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA 11Department of Dermatology, Yale School of Medicine, New Haven, CT 06510, USA 4Albert Einstein College of Medicine, Bronx, NY 10461, USA 8Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA †Correspondence to: Dr.
    [Show full text]
  • Adipose Recruitment and Activation of Plasmacytoid Dendritic Cells Fuel Metaflammation’
    Diabetes Page 2 of 61 Adipose recruitment and activation of plasmacytoid dendritic cells fuel metaflammation Amrit Raj Ghosh1, Roopkatha Bhattacharya1, Shamik Bhattacharya1, Titli Nargis2, Oindrila Rahaman1, Pritam Duttagupta1, Deblina Raychaudhuri1, Chinky Shiu Chen Liu1, Shounak Roy1, Parasar Ghosh3, Shashi Khanna4, Tamonas Chaudhuri4, Om Tantia4, Stefan Haak5, Santu Bandyopadhyay1, Satinath Mukhopadhyay6, Partha Chakrabarti2 and Dipyaman Ganguly1*. Divisions of 1Cancer Biology & Inflammatory Disorders and 2Cell Biology & Physiology, CSIR- Indian Institute of Chemical Biology, Kolkata, India; 4ILS Hospitals, Kolkata, India; 5Zentrum Allergie & Umwelt (ZAUM), Technical University of Munich and Helmholtz Centre Munich, Munich, Germany; Departments of 3Rheumatology and 6Endocrinology, Institute of Postgraduate Medical Education & Research, Kolkata, India. *Corresponding author: Dipyaman Ganguly, Division of Cancer Biology & Inflammatory Disorders, CSIR-Indian Institute of Chemical Biology, 4 Raja S C Mullick Road, Jadavpur, Kolkata, West Bengal, India, 700032. Phone: 91 33 24730492 Fax: 91 33 2473 5197 Email: [email protected] Running title: PDCs and type I interferons in metaflammation Word count (Main text): 5521 Figures: 7, Table: 1 1 Diabetes Publish Ahead of Print, published online August 25, 2016 Page 3 of 61 Diabetes ABSTRACT In obese individuals the visceral adipose tissue (VAT) becomes seat of chronic low grade inflammation (metaflammation). But the mechanistic link between increased adiposity and metaflammation remains largely
    [Show full text]
  • Adiposity, Dyslipidemia, and Insulin Resistance in Mice with Targeted Deletion of Phospholipid Scramblase 3 (PLSCR3)
    Adiposity, dyslipidemia, and insulin resistance in mice with targeted deletion of phospholipid scramblase 3 (PLSCR3) Therese Wiedmer*†, Ji Zhao*†, Lilin Li*†, Quansheng Zhou*†, Andrea Hevener‡, Jerrold M. Olefsky‡, Linda K. Curtiss§, and Peter J. Sims*†¶ Departments of *Molecular and Experimental Medicine and §Immunology, The Scripps Research Institute, La Jolla, CA 92037; and ‡Department of Medicine, University of California at San Diego, La Jolla, CA 92093-0673 Communicated by Daniel Steinberg, University of California at San Diego, La Jolla, CA, July 28, 2004 (received for review May 3, 2004) The phospholipid scramblases (PLSCR1 to PLSCR4) are a structurally portin-␣, a cofactor of the importin͞Ras͞Ran nucleopore trans- and functionally unique class of proteins, which are products of a port system (23, 24). Once imported into the nucleus, PLSCR1 tetrad of genes conserved from Caenorhabditis elegans to humans. tightly binds to genomic DNA, suggesting a possible role for this The best characterized member of this family, PLSCR1, is implicated protein in nuclear transcription (24). Consistent with a role in in the remodeling of the transbilayer distribution of plasma mem- growth factor receptor signaling, mice with targeted deletion of brane phospholipids but is also required for normal signaling PLSCR1 exhibit defects in cell maturation and proliferation, through select growth factor receptors. Mice with targeted dele- most notably affecting granulocyte production from hematopoi- tion of PLSCR1 display perinatal granulocytopenia due to defective etic precursors in response to select growth factors, and cells response of hematopoietic precursors to granulocyte colony-stim- deficient in PLSCR1 show defects in antiviral response to IFN ulating factor and stem cell factor.
    [Show full text]
  • Intra-Individual Variation of Plasma Adipokine Levels and Utility of Single Measurement of These Biomarkers in Population-Based Studies
    2464 Intra-individual Variation of Plasma Adipokine Levels and Utility of Single Measurement of These Biomarkers in Population-Based Studies Sang-Ah Lee,1 Asha Kallianpur,1 Yong-Bing Xiang,3 Wanqing Wen,1 Qiuyin Cai,1 Dake Liu,3 Sergio Fazio,2 MacRae F. Linton,2 Wei Zheng,1 and Xiao Ou Shu1 1Vanderbilt Epidemiology Center and 2Department of Medicine, Cardiovascular Division, Vanderbilt University Medical Center, Nashville, Tennessee;and 3Department of Epidemiology, Shanghai Cancer Institute, Shanghai, P.R. China Abstract Adipokines, soluble mediators produced by adipo- of a single, random sample with the mean levels from cytes, may link adipose tissue to the inflammatory, the remaining three samples using a bootstrap approach metabolic, and immune dysregulation that characterize and using intra-class correlation coefficients (ICC). many obesity-related diseases. The stability of plasma Spearman correlations between adipokine levels, age, adipokine levels within individuals, their seasonal body mass index (BMI), and waist-to-hip ratio (WHR) variability, intercorrelations, and relationships to well- were estimated. Correlations between plasma adipo- established measures of adiposity are incompletely kine levels from one random sample and the mean of defined. We measured levels of 12 adipokines [inter- the remaining three seasonal samples ranged from 0.57 leukin 1B (IL-1B), IL-6, IL-8, tumor necrosis factor-A to 0.89. Over the 1-year study period, the ICCs for (TNF-A), plasminogen activator inhibitor-1 (PAI-1), adipokine levels ranged from 0.44 (PAI-1) to 0.83 (HGF). high-sensitivity C-reactive protein (hsCRP), monocyte IL-8, MCP-1, and resistin levels were positively associ- chemoattractant protein-1 (MCP-1), nerve growth factor ated with age; HGF and PAI-1 levels were correlated (NGF), leptin, adiponectin, hepatocyte growth factor with BMI and WHR.
    [Show full text]
  • Macrophage JAK2 Deficiency Protects Against High-Fat Diet-Induced
    www.nature.com/scientificreports OPEN Macrophage JAK2 defciency protects against high-fat diet- induced infammation Received: 6 January 2017 Harsh R. Desai1,2, Tharini Sivasubramaniyam1, Xavier S. Revelo1, Stephanie A. Schroer1, Accepted: 3 July 2017 Cynthia T. Luk1, Prashanth R. Rikkala1, Adam H. Metherel3, David W. Dodington1, Yoo Jin Published: xx xx xxxx Park1, Min Jeong Kim1,4, Joshua A. Rapps1, Rickvinder Besla1, Clinton S. Robbins1,5, Kay-Uwe Wagner6, Richard P. Bazinet3, Daniel A. Winer1,2,7 & Minna Woo1,8 During obesity, macrophages can infltrate metabolic tissues, and contribute to chronic low-grade infammation, and mediate insulin resistance and diabetes. Recent studies have elucidated the metabolic role of JAK2, a key mediator downstream of various cytokines and growth factors. Our study addresses the essential role of macrophage JAK2 in the pathogenesis to obesity-associated infammation and insulin resistance. During high-fat diet (HFD) feeding, macrophage-specifc JAK2 knockout (M-JAK2−/−) mice gained less body weight compared to wildtype littermate control (M-JAK2+/+) mice and were protected from HFD-induced systemic insulin resistance. Histological analysis revealed smaller adipocytes and qPCR analysis showed upregulated expression of some adipogenesis markers in visceral adipose tissue (VAT) of HFD-fed M-JAK2−/− mice. There were decreased crown-like structures in VAT along with reduced mRNA expression of some macrophage markers and chemokines in liver and VAT of HFD-fed M-JAK2−/− mice. Peritoneal macrophages from M-JAK2−/− mice and Jak2 knockdown in macrophage cell line RAW 264.7 also showed lower levels of chemokine expression and reduced phosphorylated STAT3. However, leptin-dependent efects on augmenting chemokine expression in RAW 264.7 cells did not require JAK2.
    [Show full text]
  • Determining the Association Between Adipokine Expression in Multiple Tissues and Phenotypic Features of Non-Alcoholic Fatty Liver Disease in Obesity
    OPEN Citation: Nutrition & Diabetes (2015) 5, e146; doi:10.1038/nutd.2014.43 www.nature.com/nutd ORIGINAL ARTICLE Determining the association between adipokine expression in multiple tissues and phenotypic features of non-alcoholic fatty liver disease in obesity MGM Wolfs1,11, N Gruben1,11, SS Rensen2, FJ Verdam2, JW Greve2, A Driessen3,4, C Wijmenga5, WA Buurman6, L Franke5,7, L Scheja8, DPY Koonen1, R Shiri-Sverdlov9, TW van Haeften1,10, MH Hofker1,11 and J Fu5,11 OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is an obesity-associated disease, and in obesity adipokines are believed to be involved in the development of NAFLD. However, it is still not clear whether adipokines in the liver and/or adipose tissues can be related to the development of specific characteristics of NAFLD, such as steatosis and inflammation. We aimed to address this question by simultaneously examining the adipokine expression in three tissue types in obese individuals. METHODS: We enrolled 93 severely obese individuals with NAFLD, varying from simple steatosis to severe non-alcoholic steatohepatitis. Their expression of 48 adipokines in the liver, visceral and subcutaneous adipose tissue (SAT) was correlated to their phenotypic features of NAFLD. We further determined whether the correlations were tissue specific and/or independent of covariates, including age, sex, obesity, insulin resistance and type 2 diabetes (T2D). RESULTS: The expression of adipokines showed a liver- and adipose tissue-specific pattern. We identified that the expression of leptin, angiopoietin 2 (ANGPT2) and chemerin in visceral adipose tissue (VAT) was associated with different NAFLD features, including steatosis, ballooning, portal and lobular inflammation.
    [Show full text]
  • Circulating Adipokine Levels and Endometrial Cancer Risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
    Published OnlineFirst May 21, 2013; DOI: 10.1158/1055-9965.EPI-13-0258 Cancer Epidemiology, Research Article Biomarkers & Prevention Circulating Adipokine Levels and Endometrial Cancer Risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Patricia Luhn1,2, Cher M. Dallal1,2, Jocelyn M. Weiss3, Amanda Black1, Wen-Yi Huang1, James V. Lacey, Jr.5, Richard B. Hayes4, Frank Z. Stanczyk6, Nicolas Wentzensen1, and Louise A. Brinton1 Abstract Background: Circulating adipokine levels may be associated with endometrial cancer risk, yet few studies have evaluated these markers prospectively. Methods: We conducted a nested case–control study of postmenopausal women in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (n ¼ 78,216), including 167 incident endometrial cancer cases and 327 controls that were matched on age, study center, race, study year of diagnosis, year of blood draw, time of day of blood draw, and menopausal hormone therapy (MHT) use. Adipokine and estradiol levels were categorized into tertiles (T). ORs and 95% confidence intervals (CIs) for the associations of adiponectin, leptin, and visfatin with endometrial cancer risk were estimated by conditional logistic regression, adjusting for known endometrial cancer risk factors, including body mass index (BMI) and circulating estradiol levels. ¼ Results: Adiponectin levels were inversely associated with risk of endometrial cancer [ORT3vsT1 0.48; 95% P < P CI, 0.29–0.80); trend 0.01], whereas elevated leptin levels showed a positive association [2.77 (1.60–4.79); trend < 0.01]. These results remained significant after adjustment for estradiol, but not after further adjustment for BMI. When analyses were restricted to non-MHT users, associations of adiponectin and leptin were P ¼ stronger and remained significant after adjustment for estradiol and BMI [0.25 (0.08–0.75); trend 0.01 and P ¼ 4.72 (1.15–19.38); trend 0.02, respectively].
    [Show full text]
  • Evaluation of Fat Accumulation and Adipokine Production During The
    cells Article Evaluation of Fat Accumulation and Adipokine Production during the Long-Term Adipogenic Differentiation of Porcine Intramuscular Preadipocytes and Study of the Influence of Immunobiotics 1,2, 1,2,3, , 1,2,4, , 1,2 Asuka Tada y, AKM Humayun Kober y z, Md. Aminul Islam y z , Manami Igata , Michihiro Takagi 1,2, Masahiko Suzuki 1,2, Hisashi Aso 2,5 , Wakako Ikeda-Ohtsubo 1,2, Kazutoyo Yoda 6, Kenji Miyazawa 6, Fang He 6, Hideki Takahashi 7,8 , Julio Villena 1,9,* and Haruki Kitazawa 1,2,* 1 Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan; [email protected] (A.T.); [email protected] (A.H.K.); [email protected] (M.A.I.); [email protected] (M.I.); [email protected] (M.T.); [email protected] (M.S.); [email protected] (W.I.-O.) 2 Livestock Immunology Unit, International Education and Research Center for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan; [email protected] 3 Department of Dairy and Poultry Science, Chittagong Veterinary and Animal Sciences University, Chittagong 4225, Bangladesh 4 Department of Medicine, Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh 5 Cell Biology Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan 6 Technical Research Laboratory, Takanashi Milk Products Co., Ltd., Yokohama Kanagawa
    [Show full text]
  • Iron Metabolism in Obesity and Metabolic Syndrome
    International Journal of Molecular Sciences Review Iron Metabolism in Obesity and Metabolic Syndrome Álvaro González-Domínguez 1 , Francisco M. Visiedo-García 1 , Jesús Domínguez-Riscart 2, Raúl González-Domínguez 3 , Rosa M. Mateos 1,4 and Alfonso María Lechuga-Sancho 1,2,5,* 1 Inflammation, Nutrition, Metabolism and Oxidative Stress Study Group (INMOX), Biomedical Research and Innovation Institute of Cádiz (INiBICA), Research Unit, Puerta del Mar University Hospital, 11009 Cádiz, Spain; [email protected] (Á.G.-D.); [email protected] (F.M.V.-G.); [email protected] (R.M.M.) 2 Pediatric Endocrinology, Department of Pediatrics, Puerta del Mar University Hospital, 11009 Cádiz, Spain; [email protected] 3 Department of Chemistry, Faculty of Experimental Sciences, University of Huelva, 21007 Huelva, Spain; [email protected] 4 Area of Biochemistry and Molecular Biology, Department of Biomedicine, Biotechnology and Public Health, University of Cádiz, 11519 Cádiz, Spain 5 Area of Pediatrics, Department of Child and Mother Health and Radiology, Medical School, University of Cádiz, 11002 Cádiz, Spain * Correspondence: [email protected]; Tel.: +34-956-002-700 Received: 2 July 2020; Accepted: 29 July 2020; Published: 1 August 2020 Abstract: Obesity is an excessive adipose tissue accumulation that may have detrimental effects on health. Particularly, childhood obesity has become one of the main public health problems in the 21st century, since its prevalence has widely increased in recent years. Childhood obesity is intimately related to the development of several comorbidities such as nonalcoholic fatty liver disease, dyslipidemia, type 2 diabetes mellitus, non-congenital cardiovascular disease, chronic inflammation and anemia, among others.
    [Show full text]