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Leptin and fibrosis

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https://www.readbyqxmd.com/read/29570794/understanding-deregulated-cellular-and-molecular-dynamics-in-the-hematopoietic-stem-cell-niche-to-develop-novel-therapeutics-in-bone-marrow-fibrosis
#1
REVIEW
Hélène F E Gleitz, Rafael Kramann, Rebekka K Schneider
Bone marrow fibrosis is the continuous replacement of blood forming cells in the bone marrow by excessive scar tissue, leading to failure of the body to produce blood cells and ultimately to death. Myofibroblasts are fibrosis-driving cells and well characterized in solid organ fibrosis but their role and cellular origin in bone marrow fibrosis has remained obscure. Recent work has demonstrated that Gli1+ and Leptin Receptor+ mesenchymal stromal cells are progenitors of fibrosis-causing myofibroblasts in the bone marrow...
March 23, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29548749/leptin-up-regulates-microrna-27a-b-3p-level-in-hepatic-stellate-cells
#2
Ziqiang Li, Li Ji, Shengyan Su, Xiaofei Zhu, Fangyun Cheng, Xin Jia, Qian Zhou, Yajun Zhou
Obese patients, often accompanied by hyperleptinemia, are prone to liver fibrogenesis. Leptin is an adipocyte-derived hormone and plays a promotion role in liver fibrosis. Sterol regulatory element binding protein-1c (SREBP1c) exerts a crucial role in inhibiting hepatic stellate cell (HSC) activation, a key step in liver fibrogenesis. Our previous studies indicated that leptin inhibited SREBP1c expression, contributing to leptin-induced HSC activation and liver fibrosis. microRNAs (miR) have emerged as important layers of regulatory control and regulate gene expression, and are implicated in numerous diseases...
March 13, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29548286/relationships-between-epicardial-adipose-tissue-thickness-and-adipo-fibrokine-indicator-profiles-post-myocardial-infarction
#3
Olga Gruzdeva, Evgenya Uchasova, Yulia Dyleva, Daria Borodkina, Olga Akbasheva, Ekaterina Belik, Viktoria Karetnikova, Natalia Brel, Alexander Kokov, Vasiliy Kashtalap, Olga Barbarash
BACKGROUND: Determination of the impact of visceral obesity and epicardial adipose tissue thickness on stimulating growth factor levels during hospitalization for myocardial infarction is of potential importance for predicting outcomes and assessing the development of cardiofibrotic changes associated with maladaptive myocardial remodeling. In this study, we aimed to investigate the relationships between epicardial adipose tissue thickness, adipokine profiles, and the stimulating growth factor 2/interleukin-33 signaling system during hospitalization for myocardial infarction, and with the cardiac fibrosis extent 1-year post-MI in patients with visceral obesity...
March 16, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29524411/leptin-promotes-pulmonary-fibrosis-development-by-inhibiting-autophagy-via-pi3k-akt-mtor-pathway
#4
Xianhua Gui, Lingyun Sun, Luo Gu, Hourong Cai, Hongwei Chen
Leptin, a protein-related product of the obesity gene, plays an important role in the pathogenesis of fibrotic diseases including pulmonary fibrosis. As a highly conservative process, autophagy regulates various biological functions. Otherwise, insufficient autophagy has been described in alveolar epithelial cells (AEC) to cope with the progression of pulmonary fibrosis. Hence, this study is to investigate the effects of leptin on fibrosis in TGF-β1 induced epithelial mesenchymal transition (EMT) and the potential roles of autophagy in this processes...
March 7, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29493068/derangements-in-adrenergic-adipokine-signalling-establish-a-neurohormonal-basis-for-obesity-related-heart-failure-with-a-preserved-ejection-fraction
#5
REVIEW
Milton Packer
Among patients with heart failure and a preserved ejection (HFpEF), obesity is associated with a distinct phenotype that is characterized by adiposity-driven plasma volume expansion and cardiac overfilling, which is coupled with an impairment of ventricular distensibility. These pathophysiological abnormalities may be related to the increased actions of specific adipocyte-derived signalling molecules (aldosterone, neprilysin and leptin) that work in concert with increased renal sympathetic nerve traffic and activated beta2 -adrenergic receptors to promote sodium retention, microvascular rarefaction, cardiac fibrosis and systemic inflammation...
March 1, 2018: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29483593/human-epicardial-adipose-tissue-ctgf-expression-is-an-independent-risk-factor-for-atrial-fibrillation-and-highly-associated-with-atrial-fibrosis
#6
Qing Wang, Wang Xi, Liang Yin, Jing Wang, Hua Shen, Yang Gao, Jie Min, Yufeng Zhang, Zhinong Wang
Epicardial adipose tissue (EAT) is associated with the incidence, perpetuation, and recurrence of atrial fibrillation (AF), with elusive underlying mechanisms. We analyzed adipokine expression in samples from 20 patients with sinus rhythm (SR) and 16 with AF. Quantitative real-time PCR showed that connective tissue growth factor (cTGF) expression was significantly higher in EAT than in subcutaneous adipose tissue (SAT) or paracardial adipose tissue (PAT) from patients with AF, and in EAT from patients with SR (P < 0...
February 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29449623/targeted-disruption-of-the-inos-gene-improves-adipose-tissue-inflammation-and-fibrosis-in-leptin-deficient-ob-ob-mice-role-of-tenascin-c
#7
S Becerril, A Rodríguez, V Catalán, L Méndez-Giménez, B Ramírez, N Sáinz, M Llorente, X Unamuno, J Gómez-Ambrosi, G Frühbeck
BACKGROUND/OBJECTIVES: Obesity is related to a dynamic extracellular matrix (ECM) remodeling, which involves the synthesis and degradation of different proteins, such as tenascin C (TNC) in the adipose tissue (AT). Given the functional relationship between leptin and inducible nitric oxide synthase (iNOS), our aim was to analyze the impact of the absence of the iNOS gene in AT inflammation and ECM remodeling in ob/ob mice. SUBJECTS/METHODS: The expression of genes involved in inflammation and ECM remodeling was evaluated in 10-week-old male double knockout (DBKO) mice simultaneously lacking the ob and iNOS genes as well as in ob/ob mice classified into three groups [control, leptin-treated (1 mg kg -1 day -1 ) and pair-fed]...
February 15, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29445374/the-immunome-in-two-inherited-forms-of-pulmonary-fibrosis
#8
Souheil El-Chemaly, Foo Cheung, Yuri Kotliarov, Kevin J O'Brien, William A Gahl, Jinguo Chen, Shira Y Perl, Angélique Biancotto, Bernadette R Gochuico
The immunome (immune cell phenotype, gene expression, and serum cytokines profiling) in pulmonary fibrosis is incompletely defined. Studies focusing on inherited forms of pulmonary fibrosis provide insights into mechanisms of fibrotic lung disease in general. To define the cellular and molecular immunologic phenotype in peripheral blood, high-dimensional flow cytometry and large-scale gene expression of peripheral blood mononuclear cells and serum proteomic multiplex analyses were performed and compared in a cohort with familial pulmonary fibrosis (FPF), an autosomal dominant disorder with incomplete penetrance; Hermansky-Pudlak syndrome pulmonary fibrosis (HPSPF), a rare autosomal recessive disorder; and their unaffected relatives...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29436483/leptin-induced%C3%A2-inflammation-by-activating-il-6-expression-contributes-to-the-fibrosis-and-hypertrophy-of-ligamentum-flavum-in-lumbar-spinal-canal-stenosis
#9
Chao Sun, Zhen Wang, Jiwei Tian, Yunhao Wang
The ongoing chronic inflammation and subsequent fibrosis play an important role in ligamentum flavum(LF) fibrosis and hypertrophy in patients with lumbar spinal canal stenosis (LSCS). Leptin is a chronic inflammatory mediator and involved in the fibrotic process in multiple organ systems. The present study aimed to investigate the role of leptin in LFfibrosis and its related regulatory mechanisms. The LF specimens were obtained during the surgery from 12 patients with LSCS(LSCS group) and 12 control patients with lumbar disc herniation (LDH group)...
February 7, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29366406/preparation-of-potent-leptin-receptor-antagonists-and-their-therapeutic-use-in-mouse-models-of-uremic-cachexia-and-kidney-fibrosis
#10
Robert H Mak, Wai W Cheung, Gili Solomon, Arieh Gertler
Leptin antagonists (L39A/D40A/F4lA mutants) of mouse, human, rat and ovine leptins were developed in our laboratory by rational mutagenesis, expressed in Escherichia coli, refolded and purified to homogeneity. Pegylation of these antagonists resulted in long-acting reagents suitable for in-vivo studies. Further selection of high-affinity leptin antagonists was achieved by random mutagenesis of the whole open reading frame followed by yeast-surface display; an additional mutation (D23L) increased their affinity toward leptin receptor 60-fold...
January 24, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29359851/do-sodium-glucose-co-transporter-2-inhibitors-prevent-heart-failure-with-a-preserved-ejection-fraction-by-counterbalancing-the-effects-of-leptin-a-novel-hypothesis
#11
Milton Packer
Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of serious heart failure events in patients with type 2 diabetes, but little is known about mechanisms that might mediate this benefit. The most common heart failure phenotype in type 2 diabetes is obesity-related heart failure with a preserved ejection fraction (HFpEF). It has been hypothesized that the synthesis of leptin in this disorder leads to sodium retention and plasma volume expansion as well as to cardiac and renal inflammation and fibrosis...
January 23, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29338271/analytical-anthropometric-and-dietary-factors-associated-with-the-development-of-fibrosis-in-patients-with-nonalcoholic-fatty-liver-disease
#12
Sara Gómez de la Cuesta, Rocío Aller de la Fuente, Carla Tafur Sánchez, Olatz Izaola, Concepción García Sánchez, Natalia Mora, Jose Manuel González Hernández, Daniel de Luis Román
BACKGROUND: A prolonged non-alcoholic steatohepatitis (NASH) condition can lead to advanced stages of liver disease and the development of hepatocellular carcinoma. AIM: To evaluate analytical, anthropometric and dietary factors associated with the presence of fibrosis as this is the factor that most influences survival and evolution. METHODS: Seventy-six patients with liver biopsy-diagnosed non-alcoholic fatty liver disease (NAFLD) were included...
January 17, 2018: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/29248466/leptin-suppresses-microrna-122-promoter-activity-by-phosphorylation-of-foxo1-in-hepatic-stellate-cell-contributing-to-leptin-promotion-of-mouse-liver-fibrosis
#13
Qing Cao, Xiaofei Zhu, Xuguang Zhai, Li Ji, Fangyun Cheng, Yiqi Zhu, Pengfei Yu, Yajun Zhou
Adipocytokine leptin promotes hepatic stellate cell (HSC) activation (a key step in liver fibrogenesis) and liver fibrosis. microRNA-122 (miR-122) is the most abundant liver-specific miRNA and was demonstrated to inhibit liver fibrosis and reduced HSC proliferation. Our previous study revealed that leptin reduced miR-122 level in HSCs. This study was aimed to investigate whether leptin affected miR-122 promoter and the underlying mechanisms in HSCs. Results showed that leptin inhibited miR-122 promoter activity...
January 15, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29248461/knockout-of-l-histidine-decarboxylase-prevents-cholangiocyte-damage-and-hepatic-fibrosis-in-mice-subjected-to-high-fat-diet-feeding-via-disrupted-histamine-leptin-signaling
#14
Lindsey Kennedy, Laura Hargrove, Jennifer Demieville, Jennifer M Bailey, Wasim Dar, Kishore Polireddy, Qingzheng Chen, Moises I Nevah Rubin, Amelia Sybenga, Sharon DeMorrow, Fanyin Meng, Lindsey Stockton, Gianfranco Alpini, Heather Francis
Feeding a high-fat diet (HFD) coupled with sugar, mimicking a Western diet, causes fatty liver disease in mice. Histamine induces biliary proliferation and fibrosis and regulates leptin signaling. Wild-type (WT) and l-histidine decarboxylase (Hdc-/- ) mice were fed a control diet or an HFD coupled with a high fructose corn syrup equivalent. Hematoxylin and eosin and Oil Red O staining were performed to determine steatosis. Biliary mass and cholangiocyte proliferation were evaluated by immunohistochemistry. Senescence and fibrosis were measured by quantitative PCR and immunohistochemistry...
March 2018: American Journal of Pathology
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
#15
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...
January 1, 2018: 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
#16
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
#17
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
#18
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...
January 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29154902/dipeptidyl-peptidase-iv-dpp-iv-inhibition-prevents-fibrosis-in-adipose-tissue-of-obese-mice
#19
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...
March 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29054053/leptin-reduces-microrna-122-level-in-hepatic-stellate-cells-in-vitro-and-in-vivo
#20
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)...
December 2017: Molecular Immunology
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