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Leptin and fibrosis

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https://www.readbyqxmd.com/read/29197497/delta-like-homolog1-gata-binding-protein-2-axis-mediates-leptin-inhibition-of-ppar%C3%AE-2-expression-in-hepatic-stellate-cells-in-vitro
#1
Yuanyuan Cheng, Xiaofei Zhu, Fangyun Cheng, Li Ji, Yajun Zhou
AIMS: Peroxisome-proliferator activated receptor γ (PPARγ) plays a pivotal role in inhibition of hepatic stellate cell (HSC) activation, a key step for liver fibrogenesis. Adipocyte-derived hormone leptin has been shown to promote liver fibrosis in murine and human. PPARγ includes two subtypes, PPARγ1 and PPARγ2. Our previous study indicated that leptin down-regulated PPARγ1 expression in HSCs. The aim of this study was to investigate the effect of leptin on PPARγ2 expression and the underlying mechanisms in HSCs...
November 29, 2017: Life Sciences
https://www.readbyqxmd.com/read/29196758/the-role-of-oxidative-stress-in-the-crosstalk-between-leptin-and-mineralocorticoid-receptor-in-the-cardiac-fibrosis-associated-with-obesity
#2
Josué Gutiérrez-Tenorio, Gema Marín-Royo, Ernesto Martínez-Martínez, Rubén Martín, María Miana, Natalia López-Andrés, Raquel Jurado-López, Isabel Gallardo, María Luaces, José Alberto San Román, María González-Amor, Mercedes Salaices, María Luisa Nieto, Victoria Cachofeiro
We have investigated whether mineralocorticoid receptor activation can participate in the profibrotic effects of leptin in cardiac myofibroblasts, as well as the potential mechanisms involved. The presence of eplerenone reduced the leptin-induced increase in protein levels of collagen I, transforming growth factor β, connective tissue growth factor and galectin-3 and the levels of both total and mitochondrial of superoxide anion (O2.-) in cardiac myofibroblasts. Likewise, the MEK/ERK inhibitor, PD98059, and the PI3/Akt inhibitor, LY294002, showed a similar pattern...
December 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29177105/investigating-molecular-connections-of-non-alcoholic-fatty-liver-disease-with-associated-pathological-conditions-in-west-virginia-for-biomarker-analysis
#3
Dana L Sharma, Hari Vishal Lakhani, Rebecca L Klug, Brian Snoad, Rawan El-Hamdani, Joseph I Shapiro, Komal Sodhi
Non-alcoholic fatty liver disease (NAFLD) is a disease characterized by a steatosis of the liver that may progress to more serious pathological conditions including: nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. As the prevalence of NAFLD has increased worldwide in recent years, pathophysiology and risk factors associated with disease progression of NAFLD are at the focus of many studies. NAFLD is related to and shares common serum biomarkers with cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), obesity, and metabolic syndrome (MetS)...
October 2017: Journal of Clinical & Cellular Immunology
https://www.readbyqxmd.com/read/29156528/actein-ameliorates-hepatic-steatosis-and-fibrosis-in-high-fat-diet-induced-nafld-by-regulation-of-insulin-and-leptin-resistant
#4
Hong-Jun Chen, Jin Liu
Insulin and leptin resistance are highly involved in metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Presently, no approved treatment is available. Actein is isolated from the rthizomes of Cimicifuga foetida, a triterpene glycoside, exhibiting important biological properties, such as anti-inflammatory, anti-cancer, and anti-oxidant activity. However, its effects on metabolic syndrome are poorly understood. The aims of the study were mainly to investigate the molecular mechanisms regulating insulin and leptin resistance, and lipogenic action of actein in high fat diet-fed mice...
November 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29154902/dipeptidyl-peptidase-iv-dpp-iv-inhibition-prevents-fibrosis-in-adipose-tissue-of-obese-mice
#5
Ana Patrícia Marques, Janete Cunha-Santos, Helena Leal, Lígia Sousa-Ferreira, Luís Pereira de Almeida, Cláudia Cavadas, Joana Rosmaninho-Salgado
BACKGROUND: During the development of obesity the expansion of white adipose tissue (WAT) leads to a dysregulation and an excessive remodeling of extracellular matrix (ECM), leading to fibrosis formation. These ECM changes have high impact on WAT physiology and may change obesity progression. Blocking WAT fibrosis may have beneficial effects on the efficacy of diet regimen or therapeutical approaches in obesity. Since dipeptidyl peptidase IV (DPP-IV) inhibitors prevent fibrosis in tissues, such as heart, liver and kidney, the objective of this study was to assess whether vildagliptin, a DPP-IV inhibitor, prevents fibrosis in WAT in a mouse model of obesity, and to investigate the mechanisms underlying this effect...
November 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29054053/leptin-reduces-microrna-122-level-in-hepatic-stellate-cells-in-vitro-and-in-vivo
#6
Xuguang Zhai, Fangyun Cheng, Li Ji, Xiaofei Zhu, Qing Cao, Yali Zhang, Xin Jia, Qian Zhou, Wei Guan, Yajun Zhou
Obese patients, often accompanied by hyperleptinemia, are more likely to develop liver fibrosis. Leptin, an adipocyte-derived hormone, augments inflammatory in liver and promotes hepatic stellate cell (HSC) activation (a key step for liver fibrogenesis) and liver fibrosis. microRNA-122 (miR-122) is the most abundant liver-specific miRNA and can attenuate liver fibrosis. This study examined the effect of leptin on miR-122 level in HSCs in vivo and in vitro. Results demonstrated that leptin reduced the levels of both miR-122 (mature miR-122) and primary miR-122 (pri-miR-122)...
October 17, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29051043/lysyl-oxidase-and-adipose-tissue-dysfunction
#7
Emilie Pastel, Emily Price, Kajsa Sjöholm, Laura J McCulloch, Nikolaj Rittig, Neil Liversedge, Bridget Knight, Niels Moller, Per-Arne Svensson, Katarina Kos
BACKGROUND/OBJECTIVES: Lysyl oxidase (LOX) is an enzyme crucial for collagen fibre crosslinking and thus for fibrosis development. Fibrosis is characterised by a surplus of collagen fibre accumulation and is amongst others also a feature of obesity-associated dysfunctional adipose tissue (AT) which has been linked with type 2 diabetes. We hypothesised that in type 2 diabetes and obesity LOX expression and activity will be increased as a consequence of worsening AT dysfunction. This study aimed to provide a comprehensive characterisation of LOX in human AT...
October 16, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28994542/-mechanism-of-ezhu-containing-serum-in-inhibiting-expression-of-shh-and-gli1-in-hepatic-stellate-cells
#8
Li-Li Feng, Wen-Fu Cao
To explore the mechanism of Ezhu-containing serum in inhibiting the expression of sonic hedgehog(Shh) and glioma-associated oncogene homolog-1(Gli1) in hepatic stellate cells(HSCs) induced by leptin. Twenty sprague-dawley (SD) rats were randomly divided into 2 groups (n=10), and given Ezhu-decoction and physiological saline by gavage for 10 days to prepare drug-containing serums. The HSCs during the exponential growth phase were divided into 7 groups: blank control group, model group, hedgehog pathway inhibitor(cyclopamine) group, Ezhu group, Ezhu and cyclopamine group, hedgehog pathway agonost(pumorphamine) group, Ezhu and purmorphamine group...
March 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28976809/lepr-cells-dispute-hegemony-with-gli1-cells-in-bone-marrow-fibrosis
#9
Isadora F G Sena, Isabella T Borges, Luiza Lousado, Patrick O Azevedo, Julia P Andreotti, Viviani M Almeida, Ana E Paiva, Gabryella S P Santos, Daniel A P Guerra, Pedro H D M Prazeres, Luanny Souto, Akiva Mintz, Alexander Birbrair
Bone marrow fibrosis is a reactive process, and a central pathological feature of primary myelofibrosis. Revealing the origin of fibroblastic cells in the bone marrow is crucial, as these cells are considered an ideal, and essential target for anti-fibrotic therapy. In 2 recent studies, Decker et al. (2017) and Schneider et al. (2017), by using state-of-the-art techniques including in vivo lineage-tracing, provide evidence that leptin receptor (LepR)-expressing and Gli1-expressing cells are responsible for fibrotic tissue deposition in the bone marrow...
October 4, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28962213/effects-of-telmisartan-on-improving-leptin-resistance-and-inhibiting-hepatic-fibrosis-in-rats-with-non-alcoholic-fatty-liver-disease
#10
Qiu-Zan Zhang, Ying-Li Liu, Yan-Rong Wang, Li-Na Fu, Jing Zhang, Xiu-Ru Wang, Bang-Mao Wang
The present study aimed to investigate the impacts of telmisartan (TEL) on hepatic fibrosis, serum leptin, leptin protein in liver tissue and its mRNA expression level in rats with non-alcoholic fatty liver disease (NAFLD). Male Sprague Dawley rats were randomly divided into the control (N), model (M), polyene phosphatidylcholine (P) and TEL (T) groups. Group M and the intervention groups were given a high-fat diet for 12 weeks to induce NAFLD, followed by 4 weeks of intragastric administration of normal saline (1...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28957567/infrapatellar-fat-pad-features-in-osteoarthritis-a-histopathological-and-molecular-study
#11
Marta Favero, Hamza El-Hadi, Elisa Belluzzi, Marnie Granzotto, Andrea Porzionato, Gloria Sarasin, Anna Rambaldo, Claudio Iacobellis, Augusto Cigolotti, Chiara Giulia Fontanella, Arturo Natali, Roberta Ramonda, Pietro Ruggieri, Raffaele De Caro, Roberto Vettor, Marco Rossato, Veronica Macchi
Objective: The infrapatellar fat pad (IFP) is considered a local producer of adipocytokines, suggesting a potential role in OA. The objective of this study was to evaluate the histopathological and molecular characteristics of OA IFPs compared with controls. Methods: The histopathological characteristics of IFPs were evaluated in patients undergoing total knee replacements and in control patients (without OA), considering the following parameters: presence of inflammatory cells, vascularization, adipose lobules dimension and thickness of the interlobular septa...
October 1, 2017: Rheumatology
https://www.readbyqxmd.com/read/28938479/pulmonary-function-and-sleep-breathing-two-new-targets-for-type-2-diabetes-care
#12
Albert Lecube, Rafael Simó, Maria Pallayova, Naresh M Punjabi, Carolina López-Cano, Cecilia Turino, Cristina Hernández, Ferran Barbé
Population based studies showing the negative impact of type 2 diabetes (T2D) on lung function are overviewed. Among the well-recognized pathophysiological mechanisms, the metabolic pathways related to insulin resistance, low-grade chronic inflammation, leptin resistance, microvascular damage, and autonomic neuropathy are emphasized. Histopathological changes are exposed, and findings reported from experimental models are clearly differentiated from those described in humans. The accelerated decline in pulmonary function that appears in patients with cystic fibrosis with related abnormalities of glucose tolerance and diabetes is considered as an example to further investigate the relationship between T2D and the lung...
September 4, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28902410/monascus-fermented-red-mold-dioscorea-protects-mice-against-alcohol-induced-liver-injury-whereas-its-metabolites-ankaflavin-and-monascin-regulate-ethanol-induced-peroxisome-proliferator-activated-receptor-%C3%AE-and-sterol-regulatory-element-binding-transcription
#13
Chih-Fu Cheng, Tzu-Ming Pan
BACKGROUND: Alcoholic hepatitis is a necroinflammatory process that is associated with fibrosis and leads to cirrhosis in 40% of cases. The hepatoprotective effects of red mold dioscorea (RMD) from Monascus purpureus NTU 568 were evaluated in vivo using a mouse model of chronic alcohol-induced liver disease (ALD). RESULTS: ALD mice were orally administered vehicle (ALD group) or vehicle plus 307.5, 615.0 or 1537.5 mg kg(-1) (1 ×, 2 × and 5 ×) RMD for 5 weeks...
September 13, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28880885/markers-of-intestinal-permeability-are-already-altered-in-early-stages-of-non-alcoholic-fatty-liver-disease-studies-in-children
#14
Anika Nier, Anna Janina Engstler, Ina Barbara Maier, Ina Bergheim
BACKGROUND & AIMS: Recent studies have shown that patients with manifest non-alcoholic fatty liver disease (NAFLD), e.g. steatosis grade 3 or steatohepatitis with or without beginning fibrosis frequently show altered fecal microbiota composition and elevated bacterial endotoxin levels. However, if these alterations are signs of a progressing disease or are already found in initial disease stages has not yet been clarified. METHODS: Twenty children with simple steatosis (grade 1) diagnosed by ultrasound and 29 normal weight healthy control children (age <10 years) were included in the study (mean age 7...
2017: PloS One
https://www.readbyqxmd.com/read/28869040/the-impact-of-obesity-in-the-cardiac-lipidomic-and-its-consequences-in-the-cardiac-damage-observed-in-obese-rats
#15
Gema Marín-Royo, Ernesto Martínez-Martínez, Beatriz Gutiérrez, Raquel Jurado-López, Isabel Gallardo, Olimpio Montero, Mª Visitación Bartolomé, José Alberto San Román, Mercedes Salaices, María Luisa Nieto, Victoria Cachofeiro
AIMS: To explore the impact of obesity on the cardiac lipid profile in rats with diet-induced obesity, as well as to evaluate whether or not the specific changes in lipid species are associated with cardiac fibrosis. METHODS: Male Wistar rats were fed either a high-fat diet (HFD, 35% fat) or standard diet (3.5% fat) for 6 weeks. Cardiac lipids were analyzed using by liquid chromatography-tandem mass spectrometry. RESULTS: HFD rats showed cardiac fibrosis and enhanced levels of cardiac superoxide anion (O2), HOMA index, adiposity, and plasma leptin, as well as a reduction in those of cardiac glucose transporter (GLUT 4), compared with control animals...
August 28, 2017: Clínica e Investigación en Arteriosclerosis
https://www.readbyqxmd.com/read/28852205/probiotics-administration-following-sleeve-gastrectomy-surgery-a-randomized-double-blind-trial
#16
S Sherf-Dagan, S Zelber-Sagi, G Zilberman-Schapira, M Webb, A Buch, A Keidar, A Raziel, N Sakran, D Goitein, N Goldenberg, J A Mahdi, M Pevsner-Fischer, N Zmora, M Dori-Bachash, E Segal, E Elinav, O Shibolet
BACKGROUND: Probiotics are commonly used after bariatric surgery; however uncertainty remains regarding their efficacy. Our aim was to compare the effect of probiotics vs. placebo on hepatic, inflammatory and clinical outcomes following laparoscopic sleeve gastrectomy (LSG). METHODS: This randomized, double-blind, placebo-controlled, trial of 6-months treatment with probiotics (Bio-25;Supherb) vs. placebo and 6-months of additional follow-up was conducted among 100 morbidly obese non-alcoholic fatty liver disease (NAFLD) patients who underwent LSG surgery...
August 30, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28804632/the-pattern-of-il-24-mda-7-and-its-cognate-receptors-expression-following-activation-of-human-hepatic-stellate-cells
#17
Iman Jamhiri, Seyed Younes Hosseini, Davood Mehrabani, Zahra Khodabandeh, Ramin Yaghobi, Razieh Dowran, Saber Zahri
Activation of hepatic stellate cells (HSCs) is the pivotal event during liver fibrosis. Interleukin (IL)-24/melanoma differentiation-associated gene-7 (mda-7) has attracted attention in the pathophysiology of some diseases, while its role in activation/suppression of human HSCs is still unclear. It is important to elucidate whether the expression levels of the IL-24/mda-7 protein and its receptors in HSC cells are changed following activation. LX-2 cells, a human hepatic stellate cell line were activated by a combination of leptin and serum starvation...
August 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28791501/skeletal-muscle-mass-to-visceral-fat-area-ratio-is-an-important-determinant-affecting-hepatic-conditions-of-non-alcoholic-fatty-liver-disease
#18
Takashi Shida, Kentaro Akiyama, Sechang Oh, Akemi Sawai, Tomonori Isobe, Yoshikazu Okamoto, Kazunori Ishige, Yuji Mizokami, Kenji Yamagata, Kojiro Onizawa, Hironori Tanaka, Hiroko Iijima, Junichi Shoda
BACKGROUND: Not only obesity but also sarcopenia is associated with NAFLD. The influence of altered body composition on the pathophysiology of NAFLD has not been fully elucidated. The aim of this study is to determine whether skeletal muscle mass to visceral fat area ratio (SV ratio) affects NAFLD pathophysiology. METHODS: A total of 472 subjects were enrolled. The association between SV ratio and NAFLD pathophysiological factors was assessed in a cross-sectional nature by stratification analysis...
August 8, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28779894/identification-of-novel-cytokine-biomarkers-of-hexanal-exposure-associated-with-pulmonary-toxicity
#19
Yoon Cho, Mi-Kyung Song, Tae Sung Kim, Jae-Chun Ryu
We aimed to investigate whether exposure to low-molecular-weight saturated aliphatic aldehydes induces an airway inflammation related to lung toxicity. In previous studies, we identified that several aldehydes induced inflammatory responses through the secretion of pro-inflammatory cytokines. Here, we elucidate on whether hexanal exposure induces the lung inflammatory response through the secretion of cytokines. Hexanal is one of the aldehydes, which are major components of indoor environmental irritants. Based on a multiplexed cytokine antibody array, we investigated the cytokine expression profiles to identify the significant biomarkers of hexanal exposure and to predict the possibility of adverse effects on pulmonary toxicity using in vitro and in vivo model systems...
October 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28770223/plumbagin-alleviates-capillarization-of-hepatic-sinusoids-in-vitro-by-downregulating-et-1-vegf-ln-and-type-iv-collagen
#20
Guiyu Li, Yue Peng, Tiejian Zhao, Jiyong Lin, Xuelin Duan, Yanfei Wei, Jing Ma
Critical roles for liver sinusoidal endothelial cells (LSECs) in liver fibrosis have been demonstrated, while little is known regarding the underlying molecular mechanisms of drugs delivered to the LSECs. Our previous study revealed that plumbagin plays an antifibrotic role in liver fibrosis. In this study, we investigated whether plumbagin alleviates capillarization of hepatic sinusoids by downregulating endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), laminin (LN), and type IV collagen on leptin-stimulated LSECs...
2017: BioMed Research International
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