FNDC5 inhibits foam cell formation and monocyte adhesion in vascular smooth muscle cells via suppressing NF κB-mediated NLRP3 upregulation.

FNDC5 inhibits foam cell formation and monocyte adhesion in vascular smooth muscle cells via suppressing NFκB-mediated NLRP3 upregulation. Vascul Pharmacol. 2019 Jul 15;:106579 Authors: Zang YH, Chen D, Zhou B, Chen AD, Wang JJ, Gao XY, Chen Q, Li YH, Kang YM, Zhu GQ Abstract Foam cell formation and monocytes adhesion are key events in pathogenesis of atherosclerosis. Vascular smooth muscle cells (VSMCs) are an important origin of foam cells besides macrophages. Fibronectin type III domain containing protein 5 (FNDC5) is a protein, which induces browning of fat and attenuates glucose/lipid metabolic derangements in obese mice. The present study was designed to determine the roles of FNDC5 in inhibiting foam cell formation and monocyte adhesion in VSMCs and its underlying mechanisms. Oxidized low-density lipoprotein (oxLDL) was used to induce foam cell formation and monocyte adhesion in human aortic VSMCs. Foam cell formation was evaluated by intracellular lipid droplets, cholesterol contents, and mRNA levels of acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT-1) and ATP binding cassette transporter A-1 (ABCA-1). Monocyte adhesion was evaluated by the number of monocytes adhered to VSMCs and mRNA levels of monocyte chemotactic protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1). FNDC5 inhibited oxLDL-induced foam cell formation, monocyte adhesion, ABCA-1 mRNA downregulation, and ACAT-1, MCP-1 and VCAM-1 mRNA upregulation in VSMCs. I...
Source: Vascular Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Vascul Pharmacol Source Type: research

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Albiflorin (AF) is a small molecule (MW 481) isolated from Paeoniae radix, a plant used as a remedy for various conditions with pathogenesis shared by metabolic diseases. Reported here is our characterization of its therapeutic profiles in three mouse models with distinctive pathological features of metabolic syndrome (MetS). Our results firstly showed that AF alleviated high fat (HF) induced obesity and associated glucose intolerance, suggesting its therapeutic efficacy for MetS. In the type 2 diabetes (T2D) model induced by a combination of HF and low doses of streptozotocin, AF lowered hyperglycaemia and improved insuli...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
We examined human lung tissue from COPD patients and normal control subjects, and found a substantial increase in p16-expressing alveolar cells in COPD patients. Using a transgenic mouse deficient for p16, we demonstrated that lungs of mice lacking p16 were structurally and functionally resistant to CS-induced emphysema due to activation of IGF1/Akt regenerative and protective signaling. Fat Tissue Surrounds Skeletal Muscle to Accelerate Atrophy in Aging and Obesity https://www.fightaging.org/archives/2019/09/fat-tissue-surrounds-skeletal-muscle-to-accelerate-atrophy-in-aging-and-obesity/ Researchers her...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Alessandro Poggi1*, Roberto Benelli2, Roberta Venè1, Delfina Costa1, Nicoletta Ferrari1, Francesca Tosetti1 and Maria Raffaella Zocchi3 1Molecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 2Immunology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 3Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy It is well established that natural killer (NK) cells are involved in both innate and adaptive immunity. Indeed, they can recognize molecules induced at the cell surface by stress signals ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Ali Mahzari1, Songpei Li1, Xiu Zhou1,2, Dongli Li2, Sherouk Fouda1, Majid Alhomrani1, Wala Alzahrani1, Stephen R. Robinson1 and Ji-Ming Ye1,2* 1Lipid Biology and Metabolic Disease Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia 2School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China The present study investigated the effects of matrine on non-alcoholic steatohepatitis (NASH) in mice induced by a methionine choline-deficient (MCD) diet and the mechanism involved. The study was performed in C57B/6J mice fed a MCD diet for 6 weeks to induce NAS...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion The periconceptional environment and lifestyle factors modify sperm epigenome. This alteration might be maintained in the zygote and throughout development, thereby leading to the inheritance of newly acquired pathologies. The role of sperm miRNA, not only as innovative markers of fertility issues but also as vectors involved in the inheritance of paternal diseases, appears to be crucial. Overweight and obesity seem to alter sperm miRNA profile, thereby leading to transmission of different miRNA profiles in zygote, with consequences on embryo development. In long term, metabolic disorders have been described in...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Conclusions: The lipidome is altered in ART-treated HIV infection, and may contribute to inflammation and CVD progression. Detailed lipidomic analyses may better assess CVD risk in both HIV+ and HIV– individuals than does traditional lipid profiling. Introduction Both HIV infection and the use of antiretroviral therapy (ART) contribute to an increased risk for cardiovascular disease (CVD) (1, 2). Dyslipidemia is observed in HIV-infected (HIV+) individuals, and is associated with reduced levels of high-density lipoprotein (HDL) cholesterol, and elevated total (TC) cholesterol, low-density lipoprotein (LDL) chole...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion Activation of the Nrf2-dependent antioxidant system plays an important role in cell defense against oxidative stress damage, whereas the insufficiency of the Nrf2 system is associated with multiple aspects of the genesis and progression of metabolic diseases, posing a great risk to the cardiovascular system (Figure 1). The systemic increase of Nrf2 activity by several activators may be beneficial in the treatment of metabolic diseases. In addition, selective upregulation of Nrf2 genes may represent a potential therapy in obesity, diabetes and atherosclerosis. Looking to the future, experimental research that el...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Marcia H. Ratner, Vidhya Kumaresan and David H. Farb* Laboratory of Molecular Neurobiology, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, United States Memory dysfunction is a symptomatic feature of many neurologic and neuropsychiatric disorders; however, the basic underlying mechanisms of memory and altered states of circuitry function associated with disorders of memory remain a vast unexplored territory. The initial discovery of endogenous neurosteroids triggered a quest to elucidate their role as neuromodulators in normal and diseased brain functio...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
ConclusionThese findings reveal the role of gallic acid in E. officinalis mediated antidiabetic potential, and delineate the upregulation of pAkt, PPAR-γ and Glut4 in gallic acid mediated antidiabetic activity, thus providing potential therapy for diabetes and related disorders.Graphical Abstract
Source: Phytomedicine - Category: Drugs & Pharmacology Source Type: research
Abstract Saturated fatty acids (SFAs) activate toll-like receptor 4 (TLR4) signal transduction in macrophages and are involved in the chronic inflammation accompanying obesity. High-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I) produce anti-inflammatory effects via reverse cholesterol transport. However, the underlying mechanisms by which HDL and apoA-I inhibit inflammatory responses in adipocytes remain to be determined. Here we examined whether palmitate increases the translocation of TLR4 into lipid rafts and whether HDL and apoA-I inhibit inflammation in adipocytes. Palmitate exposure (250 &mu...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
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