scholarly journals The Roles and Associated Mechanisms of Adipokines in Development of Metabolic Syndrome

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 334
Author(s):  
Ji-Eun Kim ◽  
Jin-Sun Kim ◽  
Min-Jee Jo ◽  
Eunjung Cho ◽  
Shin-Young Ahn ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Lipid Metabolism ◽  
Foam Cell ◽  
Cell Formation ◽  
Visceral Obesity ◽  
Foam Cell Formation ◽  
Acid Oxidation ◽  
Plasminogen Activator Inhibitor 1 ◽  
Fetuin A ◽  
Pai 1

Metabolic syndrome is a cluster of metabolic indicators that increase the risk of diabetes and cardiovascular diseases. Visceral obesity and factors derived from altered adipose tissue, adipokines, play critical roles in the development of metabolic syndrome. Although the adipokines leptin and adiponectin improve insulin sensitivity, others contribute to the development of glucose intolerance, including visfatin, fetuin-A, resistin, and plasminogen activator inhibitor-1 (PAI-1). Leptin and adiponectin increase fatty acid oxidation, prevent foam cell formation, and improve lipid metabolism, while visfatin, fetuin-A, PAI-1, and resistin have pro-atherogenic properties. In this review, we briefly summarize the role of various adipokines in the development of metabolic syndrome, focusing on glucose homeostasis and lipid metabolism.

scholarly journals Foam Cells as Therapeutic Targets in Atherosclerosis with a Focus on the Regulatory Roles of Non-Coding RNAs

2021 ◽  
Vol 22 (5) ◽  
pp. 2529
Author(s):  
Amin Javadifar ◽  
Sahar Rastgoo ◽  
Maciej Banach ◽  
Tannaz Jamialahmadi ◽  
Thomas P. Johnston ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cells ◽  
Foam Cell Formation ◽  
Special Focus ◽  
Lipid Uptake ◽  
Therapeutic Goals ◽  
Expression Of Genes

Atherosclerosis is a major cause of human cardiovascular disease, which is the leading cause of mortality around the world. Various physiological and pathological processes are involved, including chronic inflammation, dysregulation of lipid metabolism, development of an environment characterized by oxidative stress and improper immune responses. Accordingly, the expansion of novel targets for the treatment of atherosclerosis is necessary. In this study, we focus on the role of foam cells in the development of atherosclerosis. The specific therapeutic goals associated with each stage in the formation of foam cells and the development of atherosclerosis will be considered. Processing and metabolism of cholesterol in the macrophage is one of the main steps in foam cell formation. Cholesterol processing involves lipid uptake, cholesterol esterification and cholesterol efflux, which ultimately leads to cholesterol equilibrium in the macrophage. Recently, many preclinical studies have appeared concerning the role of non-encoding RNAs in the formation of atherosclerotic lesions. Non-encoding RNAs, especially microRNAs, are considered regulators of lipid metabolism by affecting the expression of genes involved in the uptake (e.g., CD36 and LOX1) esterification (ACAT1) and efflux (ABCA1, ABCG1) of cholesterol. They are also able to regulate inflammatory pathways, produce cytokines and mediate foam cell apoptosis. We have reviewed important preclinical evidence of their therapeutic targeting in atherosclerosis, with a special focus on foam cell formation.

Prednisone and Its Active Metabolite Prednisolone Attenuate Lipid Accumulation in Macrophages

2019 ◽  
Vol 25 (2) ◽  
pp. 174-186
Author(s):  
Helana Jeries ◽  
Nina Volkova ◽  
Claudia Grajeda-Iglesias ◽  
Mahmoud Najjar ◽  
Mira Rosenblat ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
Cholesterol Metabolism ◽  
Foam Cell ◽  
Ex Vivo ◽  
Cholesterol Biosynthesis ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Macrophage Foam Cell ◽  
Healthy Human

Background: Synthetic forms of glucocorticoids (GCs; eg, prednisone, prednisolone) are anti-inflammatory drugs that are widely used in clinical practice. The role of GCs in cardiovascular diseases, including atherosclerosis, is highly controversial, and their impact on macrophage foam cell formation is still unknown. We investigated the effects of prednisone and prednisolone on macrophage oxidative stress and lipid metabolism. Methods and Results: C57BL/6 mice were intraperitoneally injected with prednisone or prednisolone (5 mg/kg) for 4 weeks, followed by lipid metabolism analyses in the aorta and peritoneal macrophages. We also analyzed the effect of serum samples obtained from 9 healthy human volunteers before and after oral administration of prednisone (20 mg for 5 days) on J774A.1 macrophage atherogenicity. Finally, J774A.1 macrophages, human monocyte-derived macrophages, and fibroblasts were incubated with increasing concentrations (0-200 ng/mL) of prednisone or prednisolone, followed by determination of cellular oxidative status, and triglyceride and cholesterol metabolism. Prednisone and prednisolone treatment resulted in a significant reduction in triglyceride and cholesterol accumulation in macrophages, as observed in vivo, ex vivo, and in vitro. These effects were associated with GCs’ inhibitory effect on triglyceride- and cholesterol-biosynthesis rates, through downregulation of diacylglycerol acyltransferase 1 and HMG-CoA reductase expression. Glucocorticoid-induced reduction of cellular lipid accumulation was mediated by the GC receptors on the macrophages, because the GC-receptor antagonist (RU486) abolished these effects. In fibroblasts, unlike macrophages, GCs showed no effects. Conclusion: Prednisone and prednisolone exhibit antiatherogenic activity by protecting macrophages from lipid accumulation and foam cell formation.

scholarly journals Relationship Between Autophagy and Metabolic Syndrome Characteristics in the Pathogenesis of Atherosclerosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Jing Xu ◽  
Munehiro Kitada ◽  
Yoshio Ogura ◽  
Daisuke Koya
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Molecular Mechanisms ◽  
Foam Cell ◽  
Plaque Rupture ◽  
Cell Formation ◽  
Degradation Process ◽  
Vascular Wall ◽  
Foam Cell Formation ◽  
Plaque Instability

Atherosclerosis is the main cause of mortality in metabolic-related diseases, including cardiovascular disease and type 2 diabetes (T2DM). Atherosclerosis is characterized by lipid accumulation and increased inflammatory cytokines in the vascular wall, endothelial cell and vascular smooth muscle cell dysfunction and foam cell formation initiated by monocytes/macrophages. The characteristics of metabolic syndrome (MetS), including obesity, glucose intolerance, dyslipidemia and hypertension, may activate multiple mechanisms, such as insulin resistance, oxidative stress and inflammatory pathways, thereby contributing to increased risks of developing atherosclerosis and T2DM. Autophagy is a lysosomal degradation process that plays an important role in maintaining cellular metabolic homeostasis. Increasing evidence indicates that impaired autophagy induced by MetS is related to oxidative stress, inflammation, and foam cell formation, further promoting atherosclerosis. Basal and mild adaptive autophagy protect against the progression of atherosclerotic plaques, while excessive autophagy activation leads to cell death, plaque instability or even plaque rupture. Therefore, autophagic homeostasis is essential for the development and outcome of atherosclerosis. Here, we discuss the potential role of autophagy and metabolic syndrome in the pathophysiologic mechanisms of atherosclerosis and potential therapeutic drugs that target these molecular mechanisms.

scholarly journals Overexpression of NF-κB p65 in macrophages ameliorates atherosclerosis in apoE-knockout mice

2013 ◽  
Vol 305 (11) ◽  
pp. E1375-E1383 ◽  
Author(s):  
Xin Ye ◽  
Xiaoting Jiang ◽  
Wei Guo ◽  
Katie Clark ◽  
Zhanguo Gao
Keyword(s):  
Fatty Acid ◽  
Energy Expenditure ◽  
Knockout Mice ◽  
Foam Cell ◽  
Cell Formation ◽  
Atherosclerotic Lesion ◽  
Foam Cell Formation ◽  
Acid Oxidation ◽  
Fatty Acid Binding ◽  
Apoe Knockout Mice

The transcription factor NF-κB p65 is a key regulator in the regulation of an inflammatory response and in the pathology of atherosclerosis. However, there is no direct evidence for the role of NF-κB in macrophages in the development of atherosclerosis. We investigated whether macrophage overexpression of p65 in apoE-knockout mice could improve atherosclerosis. Transgenic (Tg) mice overexpressing p65 in macrophages were generated by crossing fatty acid-binding protein 4 (aP2) promoter-controlled p65 mice with apoE-knockout (KO) mice. Tg mice exhibited functional activation of NF-κB signaling in macrophages and fat tissues. We observed that the atherosclerotic lesion was 40% less in the Tg mice compared with the apoE-KO controls fed a standard atherogenic diet for 16 wk ( n = 12). The Tg mice were leaner from reduced fat mass by increased energy expenditure. Moreover, the overexpression of p65 in macrophages suppressed foam cell formation. Our results show that there is 1) an increased fatty acid oxidation in macrophages, 2) a reduced scavenger receptor CD36 expression and lipid accumulation in microphages, 3) reduced-inflammation cytokines in serum, and 4) enhanced energy expenditure in Tg mice. Our data suggest that activation of NF-κB in macrophages has atheroprotective effects in mice by enhancing lipid metabolism and energy expenditure.

scholarly journals Vasculoprotective Effects of Vildagliptin. Focus on Atherogenesis

2020 ◽  
Vol 21 (7) ◽  
pp. 2275 ◽  
Author(s):  
Michał Wiciński ◽  
Karol Górski ◽  
Eryk Wódkiewicz ◽  
Maciej Walczak ◽  
Magdalena Nowaczewska ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Atheromatous Plaque ◽  
Macrophage Foam Cell ◽  
Serum Triglycerides ◽  
Dipeptidyl Peptidase 4 ◽  
Blood Pressure Treatment ◽  
Glucagon Like Peptide 1

Vildagliptin is a representative of Dipeptidyl Peptidase-4 (DPP-4) inhibitors, antihyperglycemic drugs, approved for use as monotherapy and combination therapy in type 2 diabetes mellitus. By inhibiting enzymatic decomposition, DPP-4 inhibitors increase the half-life of incretins such as GLP-1 (Glucagon-like peptide-1) and GIP (Gastric inhibitors polypeptide) and prolong their action. Some studies present results suggesting the anti-sclerotic and vasculoprotective effects of vildagliptin reaching beyond glycemic control. Vildagliptin is able to limit inflammation by suppression of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathway and proinflammatory agents such as TNF-α (tumor necrosis factor α), IL-1β (Interleukin-1β), and IL-8 (Interleukin 8). Moreover, vildagliptin regulates lipid metabolism; attenuates postprandial hypertriglyceridemia; and lowers serum triglycerides, apolipoprotein B, and blood total cholesterol levels. This DPP-4 inhibitor also reduces macrophage foam cell formation, which plays a key role in atheromatous plaque formation and stability. Vildagliptin reduces vascular stiffness via elevation of nitric oxide synthesis, improves vascular relaxation, and results in reduction in both systolic and diastolic blood pressure. Treatment with vildagliptin lowers the level of PAI-1 presenting possible antithrombotic effect. By affecting the endothelium, inflammation, and lipid metabolism, vildagliptin may affect the development of atherosclerosis at its various stages. The article presents a summary of the studies assessing vasculoprotective effects of vildagliptin with special emphasis on atherogenesis.

scholarly journals Astragalus flavone ameliorates atherosclerosis and hepatic steatosis via improving lipid metabolism and inhibition of inflammation in apoE-/- mice

2020 ◽  
Author(s):  
Chuanrui Ma ◽  
Jing Zhang ◽  
Shu Yang ◽  
Yunqing Hua ◽  
Jing Su ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Endothelial Dysfunction ◽  
Therapeutic Approach ◽  
Foam Cell ◽  
Cell Formation ◽  
Astragalus Membranaceus ◽  
Foam Cell Formation ◽  
Monocyte Adhesion ◽  
Lipid Disorder

Abstract Background: Atherosclerosis is a major pathogenic factor in cardiovascular diseases during the aging process. Foam cell formation and endothelial dysfunction play a key role in the initiation and development of atherosclerosis, which are affected by lipid disorder and inflammation. Therefore, the drug for inhibition of endothelial dysfunction and the subsequent foam cell formation is a therapeutic approach for atherosclerosis treatment. Total flavone of Astragalus membranaceus (TFA) is extracted from Astragalus membranaceus that has protective effect on cardiovascular disease. However, the effect of TFA on atherosclerosis and the underlying mechanism remains unknown. Methods: In this study, we determined whether TFA could inhibit atherosclerosis; and uncovered the underlying molecular mechanisms. In vivo, apoE deficient mice were treated with TFA contained in high-fat diet for 16 weeks. After treatment, aorta, macrophage and serum samples were collected to determine atherosclerotic lesions, lipid metabolism, and expression of associated genes. Concurrently, we investigated the effect of TFA on monocyte adhesion, foam cell formation, endothelial activation, and macrophage polarization in vitro and in vivo. Results: TFA reduced atherosclerotic plaque size; and enhanced lesion stability by changing the composition of plaque. Moreover, foam cell formation and its accumulation in arterial wall were attenuated by TFA, which might be attributed to improved lipid disorder, reduced inflammation, and decreased monocyte adhesion to endothelial cells. Mechanistically, TFA reduced the expression of scavenger receptor, such as CD36 and SRA; promoted the expression of ATP-binding cassette transporter A1 and G1 (ABCA1/G1). More importantly, TFA reduced the expression of miR-33, a negative regulator of cholesterol efflux as well as positive mediator on inflammation; and concurrently reduced NFkB activity, by which de-repressed ABCA1/G1 activity and inhibited the inflammation. Conclusions: This study demonstrates that TFA can attenuate atherosclerosis via dual inactivation of miR-33 and NFkB signaling pathway and inhibition of scavenger receptors (CD36 and SRA), which suggests that TFA might be a novel therapeutic approach for inhibition of atherosclerosis.

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