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Leptin and fibrosis

Wei Guan, Fangyun Cheng, Hao Wu, Qing Cao, Xiaofei Zhu, Yan Fan, Huixia Zhu, Yajun Zhou
Accumulating evidence reveals that hormone leptin, mainly produced by adipocyte, plays a unique role in promotion of liver fibrosis. Hepatic stellate cell (HSC) activation is a key step in liver fibrosis and peroxisome-proliferator activated receptor γ (PPARγ) exerts a crucial role in inhibition of HSC activation. Our previous researches demonstrated that leptin reduced PPARγ1 (a major subtype of PPARγ in HSCs) expression through GATA binding protein 2 (GATA2) binding to a site around -2323 in PPARγ1 promoter...
October 6, 2016: Journal of Cellular and Molecular Medicine
Joaquim Fernández-Solà, Ana Planavila Porta
High-dose alcohol misuse induces multiple noxious cardiac effects, including myocyte hypertrophy and necrosis, interstitial fibrosis, decreased ventricular contraction and ventricle enlargement. These effects produce diastolic and systolic ventricular dysfunction leading to congestive heart failure, arrhythmias and an increased death rate. There are multiple, dose-dependent, synchronic and synergistic mechanisms of alcohol-induced cardiac damage. Ethanol alters membrane permeability and composition, interferes with receptors and intracellular transients, induces oxidative, metabolic and energy damage, decreases protein synthesis, excitation-contraction coupling and increases cell apoptosis...
September 29, 2016: International Journal of Molecular Sciences
Mengshu Cao, Jeffery J Swigris, Xin Wang, Min Cao, Yuying Qiu, Mei Huang, Yonglong Xiao, Hourong Cai
Background. The natural history of idiopathic pulmonary fibrosis (IPF) is very complex and unpredictable. Some patients will experience acute exacerbation (AE) and fatal outcomes. Methods. The study included 30 AE-IPF patients, 32 stable IPF (S-IPF) patients, and 12 healthy controls. We measured the plasma concentrations of leptin and KL-6. Simple correlation was used to assess associations between leptin and other variables. Plasma leptin levels were compared between AE-IPF and S-IPF subjects, decedents, and survivors...
2016: Mediators of Inflammation
Gábor Koncsos, Zoltán V Varga, Tamás Baranyai, Kerstin Boengler, Susanne Rohrbach, Ling Li, Klaus-Dieter Schlüter, Rolf Schreckenberg, Tamás Radovits, Attila Oláh, Csaba Mátyás, Árpád Lux, Mahmoud Al-Khrasani, Tímea Komlódi, Nóra Bukosza, Domokos Máthé, László Deres, Monika Barteková, Tomáš Rajtík, Adriana Adameová, Krisztián Szigeti, Péter Hamar, Zsuzsanna Helyes, László Tretter, Pál Pacher, Béla Merkely, Zoltán Giricz, Rainer Schulz, Péter Ferdinandy
Although incidence and prevalence of prediabetes are increasing, little is known about its cardiac effects. Therefore, our aim was to investigate the effect of prediabetes on cardiac function and to characterize parameters and pathways associated with deteriorated cardiac performance. Long-Evans rats were fed with either control or high-fat chow for 21 wk and treated with a single low dose (20 mg/kg) of streptozotocin at week 4 High-fat and streptozotocin treatment induced prediabetes as characterized by slightly elevated fasting blood glucose, impaired glucose and insulin tolerance, increased visceral adipose tissue and plasma leptin levels, as well as sensory neuropathy...
October 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Un Ju Jung, Yu Ri Seo, Ri Ryu, Myung-Sook Choi
We compared metabolic biomarkers in the blood and peripheral blood mononuclear cell (PBMC) gene expression profiles among normal weight (BMI, 18·5-23 kg/m2), mildly obese (BMI, 25-27·5 kg/m2) and moderately obese Korean adult men (BMI, 27·5-30 kg/m2). High leptin, lipids (except LDL- and HDL-cholesterol) and apoB levels and low adiponectin and HDL-cholesterol levels were present in the plasma of both mildly and moderately obese subjects. Circulating levels of inflammatory cytokines and markers of insulin resistance, oxidative stress and liver damage were altered in moderately obese subjects but not in mildly obese subjects...
September 2016: British Journal of Nutrition
Miwa Kawanaka, Kazuhiro Nouso, Syoichiro Yano, Jun Nakamura, Ken Nishino, Mitsuhiko Suehiro, Hirofumi Kawamoto
We report the case of a 46-year-old patient who achieved remarkable improvement of characteristic non-alcoholic steatohepatitis by dieting. Initially, his body mass index (BMI) was 40.7 kg/m(2) . He proactively commenced a low calorie diet and his BMI decreased to 28 kg/m(2) after 4 years. During the same period, we performed liver biopsy four times. Liver fibrosis as well as inflammation, steatosis, and ballooning improved, and NAFLD activity score (NAS) decreased from 4 to 0. The fat deposits of liver tissue changed from macrovesicular droplets to microvesicular, and finally disappeared...
June 29, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
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
Jwa-Kyung Kim, Sun Ryoung Choi, Won Yong Lee, Mi Jin Park, Hyung Suk Lee, Young Rim Song, Hyung Jik Kim, Sung Gyun Kim
BACKGROUND: The adipocytokine leptin is an independent cardiovascular risk factor and exerts proatherogenic effect. Pre-existing vascular disease is an important cause of arteriovenous fistula (AVF) maturation failure. We explored the association between serum leptin, pre-existing vascular disease, and AVF maturation failure in incident hemodialysis patients. METHODS: Vein samples from 62 patients were collected at the time of AVF creation. Pre-existing vascular disease was evaluated with histologic changes and immunohistochemical characteristics of cellular phenotypes in intima...
April 28, 2016: Journal of Vascular Surgery
Leyla Karkhaneh, Parichehreh Yaghmaei, Kazem Parivar, Majid Sadeghizadeh, Azadeh Ebrahim-Habibi
BACKGROUND: Trans-chalcone is the precursor molecule to flavonoids and possesses antioxidant and anti-inflammatory properties. This study aimed to evaluate the effects of trans-chalcone on atheroma plaque formation and the relevant biochemical parameters in high cholesterol diet (HCD)-fed NMRI mice. METHODS: Fifty male NMRI mice were divided into 5 groups (n=10 per group): control (received a normal diet); HCD (received an additional 2% cholesterol for 18 weeks); sham (received a HCD for 12 weeks and were then shifted to a normal diet and trans-chalcone vehicle (sunflower oil) for 6 weeks), and two experimental groups (received a HCD for 12 weeks and were then shifted to a normal diet and either 12mg/kg or 24mg/kg trans-chalcone for 6 weeks)...
August 2016: Pharmacological Reports: PR
Osman Bilgin Gulcicek, Kamil Ozdogan, Ali Solmaz, Hakan Yigitbas, Serdar Altınay, Aysegul Gunes, Duygu Sultan Celik, Erkan Yavuz, Atilla Celik, Fatih Celebi
INTRODUCTION: Obesity has recently become a major health problem, and researchers have been directed to work toward the development of surgical techniques, with new mediators playing an important role in nutrition. Gastric plication (GP) and sleeve gastrectomy (SG) have become popular recently. These are widely used techniques in bariatric surgery. OBJECTIVES: In this study, we aimed to compare the efficiency of SG and GP techniques on rats. METHODS: Wistar-Hannover rats (n=18) were divided into three equal groups, namely SG, GP, and control...
2016: Food & Nutrition Research
Sonu Kashyap, Sean Engel, Mazen Osman, Yousif Al-Saiegh, Asarn Wongjarupong, Joseph P Grande
Purpose. Type 2 diabetes is the leading cause of end stage renal disease in the United States. Atherosclerotic renal artery stenosis is commonly observed in diabetic patients and impacts the rate of renal and cardiovascular disease progression. We sought to test the hypothesis that renovascular hypertension, induced by unilateral renal artery stenosis, exacerbates cardiac remodeling in leptin-deficient (db/db) mice, which serves as a model of human type II diabetes. Methods. We employed a murine model of renovascular hypertension through placement of a polytetrafluoroethylene cuff on the right renal artery in db/db mice...
2016: PeerJ
Iona Lozano, Remmelt Van der Werf, William Bietiger, Elodie Seyfritz, Claude Peronet, Michel Pinget, Nathalie Jeandidier, Elisa Maillard, Eric Marchioni, Séverine Sigrist, Stéphanie Dal
BACKGROUND: As a result of the increased consumption of sugar-rich and fatty-products, and the increase in preference for such products, metabolic disorders are becoming more common at a younger age. Fructose is particularly used in prepared foods and carbonated beverages. We investigated the impact of regular consumption of fructose, in combination or not with fatty food, on the onset of metabolic syndrome and type 2 diabetes (T2D). We evaluated the metabolic, oxidative, and functional effects on the liver and blood vessels, both related to diabetes complications...
2016: Nutrition & Metabolism
Behrouz Ilkhanizadeh, Alireza Shirpoor, Mohamad Hasan Khadem Ansari, Samira Nemati, Yusef Rasmi
BACKGROUND: Diabetic cardiomyopathy is an important causal factor in morbidity and mortality among diabetic patients, and currently, no effective means are available to reverse its pathological progress. The purpose of the present study was to investigate the effect of ginger extract on apolipoproteins (apo) A and B, hyperhomocysteinemia, cathepsin G and leptin changes, as well as cardiac fibrosis and heart muscle cell proliferation under hyperglycemic conditions in vivo. METHODS: Twenty-four male Wistar rats were divided into three groups, namely: control, non-treated diabetic, and ginger extract-treated diabetic groups...
February 2016: Diabetes & Metabolism Journal
Bryan J Heard, Nathan M Solbak, May Chung, Yamini Achari, Nigel G Shrive, Cyril B Frank, David A Hart
OBJECTIVE AND DESIGN: The health of the infrapatellar fat pad (IFP) has been linked to pain, joint inflammation, and the onset of post-traumatic osteoarthritis. Thus, early inflammation effects on the IFP could have long term sequelae on joint integrity. This study was designed to characterize the natural history of the IFP in a model of surgically induced knee injury and inflammation, and to test the efficacy of one intra-articular (IA) administration of dexamethasone (DEX) immediately following surgery...
June 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
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 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
Weilin Liu, Dicky Struik, Vera J M Nies, Angelika Jurdzinski, Liesbeth Harkema, Alain de Bruin, Henkjan J Verkade, Michael Downes, Ronald M Evans, Tim van Zutphen, Johan W Jonker
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder and is strongly associated with obesity and type 2 diabetes. Currently, there is no approved pharmacological treatment for this disease, but improvement of insulin resistance using peroxisome proliferator-activated receptor-γ (PPARγ) agonists, such as thiazolidinediones (TZDs), has been shown to reduce steatosis and steatohepatitis effectively and to improve liver function in patients with obesity-related NAFLD. However, this approach is limited by adverse effects of TZDs...
February 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
Ju Ri Ham, Hae-In Lee, Ra-Yeong Choi, Mi-Ok Sim, Kwon-Il Seo, Mi-Kyung Lee
This study examined the effects of syringic acid (SA) on obese diet-induced hepatic dysfunction. Mice were fed high-fat diet (HFD) with or without SA (0.05%, wt/wt) for 16 weeks. SA reduced the body weight, visceral fat mass, serum levels of leptin, TNFα, IFNγ, IL-6 and MCP-1, insulin resistance, hepatic lipid content, droplets and early fibrosis, whereas it elevated the circulation of adiponectin. SA down-regulated lipogenic genes (Cidea, Pparγ, Srebp-1c, Srebp-2, Hmgcr, Fasn) and inflammatory genes (Tlr4, Myd88, NF-κB, Tnfα, Il6), whereas it up-regulated fatty acid oxidation genes (Pparα, Acsl, Cpt1, Cpt2) in the liver...
February 2016: Food & Function
Enas A Abd El-Haleim, Ashraf K Bahgat, Samira Saleh
Peroxisome proliferator-activated receptors (PPARs) gamma and alpha have been shown to play key roles in maintaining glucose and lipid homeostasis by acting as insulin sensitizers and lipid-lowering agents respectively, which would make them potential candidates for the treatment of non-alcoholic steatohepatitis (NASH) characterized by insulin resistance, hyperglycemia, and hypertriglyceridemia. The effects of pioglitazone, a PPAR-γ agonist, and fenofibrate, a PPAR-α agonist, as monotherapy and in combination on the expressions of key genes linked to the development of NASH were studied in rats with fructose-induced NASH...
February 15, 2016: European Journal of Pharmacology
Ernesto Martínez-Martínez, Cristina Rodríguez, María Galán, María Miana, Raquel Jurado-López, María Visitación Bartolomé, María Luaces, Fabián Islas, José Martínez-González, Natalia López-Andrés, Victoria Cachofeiro
Lysyl oxidase (LOX) is an extracellular matrix (ECM)-modifying enzyme that has been involved in cardiovascular remodeling. We explore the impact of LOX inhibition in ECM alterations induced by obesity in the cardiovascular system. LOX is overexpressed in the heart and aorta from rats fed a high-fat diet (HFD). β-Aminopropionitrile (BAPN), an inhibitor of LOX activity, significantly attenuated the increase in body weight and cardiac hypertrophy observed in HFD rats. No significant differences were found in cardiac function or blood pressure among any group...
March 2016: Journal of Molecular and Cellular Cardiology
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