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Adipokines and fibrosis

Catarina Francisco, João Sérgio Neves, Inês Falcão-Pires, Adelino Leite-Moreira
Adiponectin is the most abundant adipokine and exhibits anti-inflammatory, antiatherogenic and antidiabetic properties. Unlike other adipokines, it inversely correlates with body weight and obesity-linked cardiovascular complications. Diastolic dysfunction is the main mechanism responsible for approximately half of all heart failure cases, the so-called heart failure with preserved ejection fraction (HFpEF), but therapeutic strategies specifically directed towards these patients are still lacking. In the last years, a link between adiponectin and diastolic dysfunction has been suggested...
October 18, 2016: Cardiovascular Drugs and Therapy
Agnieszka Zwolak, Agnieszka Szuster-Ciesielska, Jadwiga Daniluk, Justyna Semeniuk, Martyna Kandefer-Szerszen
:  Background. Chemerin and retinol binding protein-4 (RBP-4) are adipokines which may play a role in the progression of NAFLD. It has been also suggested that cytokeratin-18 (CK-18) could be a marker of hepatocyte caspase-directed death while transgelin-2 production could reflect stage of liver fibrosis. The aim of this study was to evaluate the level of the above adipokines in sera of patients with NAFLD and determine the relation between the level of transgelin-2 and fibrosis-4 index (FIB-4)...
November 2016: Annals of Hepatology
Veronika Šrámková, Lenka Rossmeislová, Eva Krauzová, Jana Kračmerová, Michal Koc, Dominique Langin, Vladimír Štich, Michaela Šiklová
CONTEXT: Beneficial metabolic effects of calorie restriction found in the early stage of hypocalorie diets may be caused by the modulation of metabolic and endocrine function of adipose tissue. OBJECTIVE: To compare metabolic and inflammation-related characteristics of subcutaneous adipose tissue (SAAT) in the early (2 days) and later (28 days) phase of VLCD. Design, Setting, Intervention and Patients: 17 moderately obese premenopausal women followed 800 kcal/d VLCD for 28 days...
October 7, 2016: Journal of Clinical Endocrinology and Metabolism
Ioannis Drosos, Georgios Chalikias, Maria Pavlaki, Dimitra Kareli, Grigorios Epitropou, Georgios Bougioukas, Dimitrios Mikroulis, Fotios Konstantinou, Alexandra Giatromanolaki, Konstantinos Ritis, Thomas Münzel, Dimitrios Tziakas, Stavros Konstantinides, Katrin Schäfer
AIM: The factors mediating the paracrine effects of perivascular adipose tissue (PVAT) in atherosclerosis are largely unknown. The adipokine leptin has been implicated in the increased cardiovascular risk in obesity and may locally promote neointima formation independently of circulating leptin levels. In patients with established coronary artery disease, we examined the expression of leptin as well as of its possible inducers in 'cardiac' PVAT surrounding the aortic root and coronary arteries (C-PVAT), and compared it to the PVAT surrounding the internal mammary artery (IMA-PVAT), a vessel resistant to atherosclerosis...
June 23, 2016: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
Raika Jamali, Mohsen Razavizade, Abbas Arj, Mohammad Hossein Aarabi
AIM: To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease. METHODS: Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm non-alcoholic liver disease (NAFLD)...
June 7, 2016: World Journal of Gastroenterology: WJG
Dariusz M Lebensztejn, Marta Flisiak-Jackiewicz, Irena Białokoz-Kalinowska, Anna Bobrus-Chociej, Irina Kowalska
Nowadays non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver pathology both in adults and children. NAFLD manifestation ranges from a simple liver steatosis to steatohepatitis (nonalcoholic steatohepatitis - NASH), which may progress to advanced fibrosis, cirrhosis and end-stage liver disease. Due to the coexistence of visceral obesity, insulin resistance and dyslipidemia, NAFLD is considered to be the hepatic manifestation of metabolic syndrome. In recent years, in the pathogenesis of metabolic syndrome, type 2 diabetes mellitus, cardiovascular disease and also NAFLD, more and more attention has been paid to the so-called organokines, proteins with both paracrine or/and endocrine activities...
2016: Acta Biochimica Polonica
Christine M Kusminski, Perry E Bickel, Philipp E Scherer
Adipose tissue regulates numerous physiological processes, and its dysfunction in obese humans is associated with disrupted metabolic homeostasis, insulin resistance and type 2 diabetes mellitus (T2DM). Although several US-approved treatments for obesity and T2DM exist, these are limited by adverse effects and a lack of effective long-term glucose control. In this Review, we provide an overview of the role of adipose tissue in metabolic homeostasis and assess emerging novel therapeutic strategies targeting adipose tissue, including adipokine-based strategies, promotion of white adipose tissue beiging as well as reduction of inflammation and fibrosis...
September 2016: Nature Reviews. Drug Discovery
J-Y Choi, R A McGregor, E-Y Kwon, Y J Kim, Y Han, J H Y Park, K W Lee, S-J Kim, J Kim, J W Yun, M-S Choi
OBJECTIVES: The aim of this study was to explore the phenotypic differences underpinning obesity susceptibility or resistance based on the metabolic and transcriptional profiling of C57BL/6J mice fed a high-fat diet (HFD). METHODS: The mice were fed either a normal diet or HFD for 12 weeks. After 6 weeks, the mice on HFD were classified as either obesity-prone (OP) or obesity-resistant (OR) depending on the body weight gain. RESULTS: Lipid profiles from plasma and liver significantly improved in OR mice relative to the OP group...
September 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Kazushi Sugimoto, Yoshiyuki Takei
Alcoholic liver disease (ALD) has become one of the most critical health problems in many countries, including Japan. Liver injury in ALD ranges from steatosis and steatohepatitis to fibrosis, cirrhosis and hepatocellular carcinoma. Many factors are thought to contribute to the development and progression of ALD, particularly insulin resistance, generation of reactive oxygen species during alcohol metabolism, adipokines from visceral adipose tissue, and endotoxin derived from the gut. Although the pathogenesis of ALD has been widely investigated, the precise mechanisms are yet to be elucidated and many questions remain...
May 3, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Dan Wu, Li Li, Li-Ling Wu
Cardiac fibrosis refers to myocardial tissue excess deposition of extracellular matrix. Excessive cardiac fibrosis can lead to cardiac diastolic dysfunction, and may eventually induce heart failure. Adipo- kines are mainly secreted by adipose tissue, can regulate glucose and lipid metabolism, inflammation, immune response and cardiovascular function. Recent study show that adipokines also involved in the oc- currence and development of cardiac fibrosis, adipokines constitute pro-fibrotic and anti-fibrosis complex regulatory networks, influence the development of cardiovascular disease and prognosis...
December 2015: Sheng Li Ke Xue Jin Zhan [Progress in Physiology]
Matteo Tardelli, Veronica Moreno-Viedma, Maximilian Zeyda, Bianca K Itariu, Felix B Langer, Gerhard Prager, Thomas M Stulnig
BACKGROUND AND AIM: Obesity is a major risk factor for liver fibrosis and tightly associated with low levels of adiponectin. Adiponectin has antifibrogenic activity protecting from liver fibrosis, which is mainly driven by activated hepatic stellate cells (HSC). Aquaporins are trans-membrane proteins which allow the movement of water and, in case of aquaglyceroporins (AQPs), of glycerol that is needed in quiescent HSC for lipogenesis. Expression of various AQPs in liver is altered by obesity, however the mechanisms through which obesity influences HSCs activation and AQPs expression remain unclear...
April 15, 2016: Journal of Gastroenterology and Hepatology
Jian Wu
Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of liver disorders with fat accumulation from simple fatty liver, nonalcoholic steatohepatitis (NASH), fibrosis/cirrhosis and NAFLD/NASH-associated hepatocellular carcinoma (HCC). NASH is a progressive form of NAFLD and requires medical attention. One of 5-10 NASH patients may progress to end-state liver disease (ESLD or cirrhosis) in 5-10 years; meanwhile, life-threatening complications of ESLD and HCC account for major mortality. An increasing burden of NAFLD in clinics, elucidation of its pathogenesis and progression, and assessment of the efficacy of potential therapeutics demand reliable animal models...
April 7, 2016: Oncotarget
Florent Eymard, Xavier Chevalier
The infrapatellar fat pad (IFP) of Hoffa's fat pad is the main adipose structure within the knee joint. It is located between the joint capsule and the synovial membrane, which lines its posterior aspect. The IFP is composed chiefly of adipocytes and receives an abundant supply of blood vessels and nerves. Immune cells can infiltrate the IFP, which can become a major source of numerous proinflammatory mediators (cytokines and adipokines). The physiological role for the IFP remains unclear but may involve shock absorption and the protection of adjacent tissues...
July 2016: Joint, Bone, Spine: Revue du Rhumatisme
Dawei Li, Tianfei Lu, Conghuan Shen, Yuan Liu, Jiang Zhang, Yuhua Shan, Yi Luo, Zhifeng Xi, Bijun Qiu, Qimin Chen, Jianjun Zhang, Qiang Xia
Fibroblast growth factor 21 is a critical circulating adipokine involving in metabolic disorders and various liver diseases. This study was performed to investigate whether FGF21 is also associated with the pathophysiology of biliary atresia. Serum FGF21 levels were measured in 57 BA patients and 20 age matched healthy controls. We also examined hepatic FGF21 mRNA expression and FGF21 protein levels in liver tissues obtained from 15 BA patients undergoing liver transplantation and 5 cases of pediatric donation after cardiac death donor without liver diseases by RT-PCR and Western blotting...
July 2016: Cytokine
Su-Kyung Shin, Su-Jung Cho, Un Ju Jung, Ri Ryu, Myung-Sook Choi
Obesity, along with its related complications, is a serious health problem worldwide. Many studies reported the anti-diabetic effect of phlorizin, while little is known about its anti-obesity effect. We investigated the beneficial effects of phlorizin on obesity and its complications, including diabetes and inflammation in obese animal. Male C57BL/6J mice were divided into three groups and fed their respective experimental diets for 16 weeks: a normal diet (ND, 5% fat, w/w), high-fat diet (HFD, 20% fat, w/w), or HFD supplemented with phlorizin (PH, 0...
February 16, 2016: Nutrients
Pil-Hoon Park, Carlos Sanz-Garcia, Laura E Nagy
Hepatic fibrosis is a dynamic process resulting from excessive deposition of extracellular matrix in the liver; uncontrolled progression of fibrosis can eventually lead to liver cirrhosis and/or hepatocellular carcinoma. The fibrogenic process is complex and modulated by a number of both hepatic and extra-hepatic biological factors. Growing evidence indicates that adipokines, a group of cytokines produced by adipose tissue, impart dynamic functions in liver and are involved in modulation of hepatic fibrosis...
December 1, 2015: Current Pathobiology Reports
Nádia Gonçalves, Ana Filipa Silva, Patrícia Gonçalves Rodrigues, Eugénia Correia, Cláudia Moura, Catarina Eloy, Roberto Roncon-Albuquerque, Inês Falcão-Pires, Adelino F Leite-Moreira
"Obesity cardiomyopathy" effects have been widely described; however, the specific contribution of metabolic changes and altered adipokine secretion are still uncharacterized. Moreover, a diagnosis based on body mass index might not be the most accurate to identify increased adiposity and its outcomes. In this study, we aimed to determine the impact of a Western-type diet [hypercaloric diet (HCD)] ingestion on biventricular structure and function, as well as the metabolic and endocrine changes that occur before the establishment of overt obesity...
March 15, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Lauren Reinke, Anna P Lam, Annette S Flozak, John Varga, Cara J Gottardi
Adiponectin is a pleiotropic adipokine implicated in obesity, metabolic syndrome and cardiovascular disease. Recent studies have identified adiponectin as a negative regulator of tissue fibrosis. Wnt/β-catenin signaling has also been implicated in metabolic syndrome and can promote tissue fibrosis, but the extent to which adiponectin cross-regulates Wnt/β-catenin signaling is unknown. Using primary human dermal fibroblasts and recombinant purified proteins, we show that adiponectin can limit β-catenin accumulation and downstream gene activation by inhibiting Lrp6 phosphorylation, a key activation step in canonical Wnt signaling...
February 12, 2016: Biochemical and Biophysical Research Communications
Ilaria Russo, Nikolaos G Frangogiannis
Both type 1 and type 2 diabetes are associated with cardiac fibrosis that may reduce myocardial compliance, contribute to the pathogenesis of heart failure, and trigger arrhythmic events. Diabetes-associated fibrosis is mediated by activated cardiac fibroblasts, but may also involve fibrogenic actions of macrophages, cardiomyocytes and vascular cells. The molecular basis responsible for cardiac fibrosis in diabetes remains poorly understood. Hyperglycemia directly activates a fibrogenic program, leading to accumulation of advanced glycation end-products (AGEs) that crosslink extracellular matrix proteins, and transduce fibrogenic signals through reactive oxygen species generation, or through activation of Receptor for AGEs (RAGE)-mediated pathways...
January 2016: Journal of Molecular and Cellular Cardiology
Mark P Jedrychowski, Libin Liu, Collette J Laflamme, Kalypso Karastergiou, Tova Meshulam, Shi-Ying Ding, Yuanyuan Wu, Mi-Jeong Lee, Steven P Gygi, Susan K Fried, Paul F Pilch
OBJECTIVE: Adipocytes are robust protein secretors, most notably of adipokines, hormone-like polypeptides, which act in an endocrine and paracrine fashion to affect numerous physiological processes such as energy balance and insulin sensitivity. To understand how such proteins are assembled for secretion we describe the function of a novel endoplasmic reticulum oxidoreductase, adiporedoxin (Adrx). METHODS: Adrx knockdown and overexpressing 3T3-L1 murine adipocyte cell lines and a knockout mouse model were used to assess the influence of Adrx on secreted proteins as well as the redox state of ER resident chaperones...
November 2015: Molecular Metabolism
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