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1.
Relevance of Leptin and Other Adipokines in Obesity-Associated Cardiovascular Risk.
Landecho, MF, Tuero, C, Valentí, V, Bilbao, I, de la Higuera, M, Frühbeck, G
Nutrients. 2019;(11)
Abstract
Obesity, which is a worldwide epidemic, confers increased risk for multiple serious conditions including type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Adipose tissue is considered one of the largest endocrine organs in the body as well as an active tissue for cellular reactions and metabolic homeostasis rather than an inert tissue only for energy storage. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a large number of hormones, cytokines, extracellular matrix proteins, and growth and vasoactive factors, which are collectively called adipokines known to influence a variety of physiological and pathophysiological processes. In the obese state, excessive visceral fat accumulation causes adipose tissue dysfunctionality that strongly contributes to the onset of obesity-related comorbidities. The mechanisms underlying adipose tissue dysfunction include adipocyte hypertrophy and hyperplasia, increased inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. This review describes the relevance of specific adipokines in the obesity-associated cardiovascular disease.
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2.
The role of new adipokines in gestational diabetes mellitus pathogenesis.
Mierzyński, R, Poniedziałek-Czajkowska, E, Dłuski, D, Leszczyńska-Gorzelak, B
Ginekologia polska. 2018;(4):221-26
Abstract
Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition dur-ing pregnancy. Explanation of the GDM pathogenesis is important due to preventing gestational complications. During pregnancy there are significant changes in maternal metabolism. Many of these changes are influenced by different adi-pokines produced in the placenta and adipose tissue. The exact role of adipokines in the pathogenesis of GDM remains still unknown. Several adipokines have been analysed throughout gestation and their levels have been suggested as biomarkers of maternal-perinatal outcomes. Some of them have been postulated as significant in the pathogenesis of pregnancy complications like GDM. This report aims to review some of the recent topics of adipokine research that may be of particular importance in patho-physiology and diagnosis of gestational diabetes mellitus. Because of manuscript length limitations, after thorough literature review and in view of the recent evidence, we focus on the one of the most well-known adipokine: adiponectin, and not so well-studied: nesfatin-1, chemerin, ghrelin, and CTRP 1.
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3.
[Sport: A key element for myometrial contractility and regulation of adipokines in obese pregnant women?].
Ghesquière, L, Hanssens, S, Leroy, A, Petit, C, Deruelle, P, Azaïs, H
Gynecologie, obstetrique, fertilite & senologie. 2018;(7-8):587-592
Abstract
Obesity is a major public health problem. Pregnant women are also affected by this epidemic. In pregnant women, obesity increases obstetric and neonatal complications, and is associated with alterations in the quality of labor that could be explained by reduced myometrial contractility. This leads to an increase in the rate of caesarean sections and postpartum haemorrhages in this population at risk. Adipokines, hormones secreted by adipose tissue, may have a role in altering the myometrial contractility. Weight loss in these patients is based on dietary management and on physical activity, which could be a way to improve adipokines action and uterine contractility. The objective of this literature review was to review current knowledge about the role of adipokines on uterine contractility in obese pregnant women and to assess the interest of sport in improving contractility and in reducing obstetric complications in these women.
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4.
Derangements in adrenergic-adipokine signalling establish a neurohormonal basis for obesity-related heart failure with a preserved ejection fraction.
Packer, M
European journal of heart failure. 2018;(5):873-878
Abstract
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. This interplay leads to striking activation of the mineralocorticoid receptor, possibly explaining why obese patients with heart failure are most likely to benefit from spironolactone and eplerenone in large-scale clinical trials. Additionally, adipocytes express and release neprilysin, which (by degrading endogenous natriuretic peptides) can further promote plasma volume expansion and cardiac fibrosis. Heightened neprilysin activity may explain the low circulating levels of natriuretic peptides in obesity, the accelerated breakdown of natriuretic peptides in HFpEF, and the cardiac decompression following neprilysin inhibition in HFpEF patients who are obese. Furthermore, as adipose tissue accumulates and becomes dysfunctional, its secretion of leptin promotes renal sodium retention, microvascular changes and fibrotic processes in the heart, and systemic inflammation; these effects may be mediated or potentiated by the activation of beta2 -adrenergic receptors. These adrenergic-adipokine interactions provide a mechanistic framework for novel therapeutic strategies to alleviate the pathophysiological abnormalities of obesity-related HFpEF. Ongoing trials are well-positioned to test this hypothesis.
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5.
Immunologic and endocrine functions of adipose tissue: implications for kidney disease.
Zhu, Q, Scherer, PE
Nature reviews. Nephrology. 2018;(2):105-120
Abstract
Excess adiposity can induce adverse sequelae in multiple cell types and organ systems. The transition from the lean to the obese state is characterized by fundamental cellular changes at the level of the adipocyte. These changes affect the local microenvironment within the respective adipose tissue but can also affect nonadipose systems. Adipocytes within fat pads respond to chronic nutrient excess through hyperplasia or hypertrophy, which can differentially affect interorgan crosstalk between various adipose depots and other organs. This crosstalk is dependent on the unique ability of the adipocyte to coordinate metabolic adjustments throughout the body and to integrate responses to maintain metabolic homeostasis. These actions occur through the release of free fatty acids and metabolites during times of energy need - a process that is altered in the obese state. In addition, adipocytes release a wide array of signalling molecules, such as sphingolipids, as well as inflammatory and hormonal factors (adipokines) that are critical for interorgan crosstalk. The interactions of adipose tissue with the kidney - referred to as the adipo-renal axis - are important for normal kidney function as well as the response of the kidney to injury. Here, we discuss the mechanistic basis of this interorgan crosstalk, which clearly has great therapeutic potential given the increasing rates of chronic kidney disease secondary to obesity and type 2 diabetes mellitus.
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6.
Leptin, An Adipokine With Central Importance in the Global Obesity Problem.
Mechanick, JI, Zhao, S, Garvey, WT
Global heart. 2018;(2):113-127
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Abstract
Leptin has central importance in the global obesity and cardiovascular disease problem. Leptin is principally secreted by adipocytes and acts in the hypothalamus to suppress appetite and food intake, increase energy expenditure, and regulate body weight. Based on clinical translation of specific and networked actions, leptin affects the cardiovascular system and may be a marker and driver of cardiometabolic risk factors with interventions that are actionable by cardiologists. Leptin subnetwork analysis demonstrates a statistically significant role for ethnoculturally and socioeconomically appropriate lifestyle intervention in cardiovascular disease. Emergent mechanistic components and potential diagnostic or therapeutic targets include hexokinase 3, urocortins, clusterin, sialic acid-binding immunoglobulin-like lectin 6, C-reactive protein, platelet glycoprotein VI, albumin, pentraxin 3, ghrelin, obestatin prepropeptide, leptin receptor, neuropeptide Y, and corticotropin-releasing factor receptor 1. Emergent associated symptoms include weight change, eating disorders, vascular necrosis, chronic fatigue, and chest pain. Leptin-targeted therapies are reported for lipodystrophy and leptin deficiency, but they are investigational for leptin resistance, obesity, and other chronic diseases.
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7.
Adipokines in rheumatoid arthritis.
Fatel, ECS, Rosa, FT, Simão, ANC, Dichi, I
Advances in rheumatology (London, England). 2018;(1):25
Abstract
Rheumatoid arthritis affects millions of people worldwide and is considered a chronic multisystem disease whose causes are unknown. In general, the main objective of rheumatoid arthritis treatment is to improve the quality of life of patients by relieving pain, maintaining or improving functional capacity, preventing thus, disability. In recent years the role of adipokines in the pathogenesis of rheumatoid arthritis has been discussed but results are still conflicting. Although results from some studies have shown the implications of adipokines in the pathophysiology of autoimmune diseases, including rheumatoid arthritis, their role in the pathogenesis of disease progression is not clear. Thus, this review aimed to describe the association of key adipokines (leptin, resistin, visfatin and adiponectin) and rheumatoid arthritis, given the high prevalence of this disease and the important social impact caused by this chronic disabling disease.
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8.
Liver fibrosis in the context of nonalcoholic steatohepatitis: the role of adipokines.
DI Maira, G, Pastore, M, Marra, F
Minerva gastroenterologica e dietologica. 2018;(1):39-50
Abstract
Liver fibrosis is a multifaceted process that occurs as a consequence of chronic liver injury. This process is characterized by inflammation, activation of matrix-producing cells, matrix deposition and remodeling, and epithelial cell regeneration. In subjects with chronic liver damage, fibrogenesis is favored by the presence of obesity and insulin resistance, which are also relevant risk factors for the development and progression of nonalcoholic steatohepatitis (NASH). It is now well-known that adipose tissue is not only involved in energy storage but also functions as an endocrine organ that secretes various bioactive substances known as adipokines. This term identifies a group of polypeptide molecules, which exert local, peripheral and/or central actions. Additionally to their well-established role in controlling adipose tissue physiology, energy homeostasis, inflammation and immune function, adipokines have been shown to be involved in different obesity-related diseases, such as hypertension, atherosclerosis and type 2 diabetes. In liver diseases, the biologic actions of these factors may contribute to the mechanisms leading to NASH. In this review, we focus on the role of adipokines in liver fibrogenesis and discuss their potential as regulators of this pathological condition and as targets for future pharmacological treatment strategies of chronic liver diseases.
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9.
[Psoriasis,Cardiovascular Disease,and Adipokines].
Yu, XL, Wu, C, Jin, HZ
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae. 2018;(4):556-562
Abstract
Psoriasis usually combines with metabolic diseases,and the prevalence of cardiovascular disease remarkably increases in psoriatic patients. Adipokines,which play an important role in the cardiovascular diseases,also express abnormally in psoriasis and may induce or exacerbate the skin lesion. The adipokines associated with psoriasis and cardiovascular disease include adiponectin,leptin,resistin,omentin,visfatin,chemerin,and retinoid binding protein 4 (RBP-4). The levels of adiponectin and omentin apparently decrease in psoriatic patients compared to healthy controls,and thus they may play protective roles for psoriasis. Similarly,adiponectin plays a protective role in cardiovascular disease,but the role of retina in cardiovascular disease is still controversial. However,the concentrations of leptin,resistin,visfatin,chemerin,and RBP-4 in patients with psoriasis or cardiovascular disease are significantly higher than those of the controls;therefore,they may serve as the pathogenic factors for both diseases. Low adiponectin,leptin,visfatin,and chemerin levels may induce or aggravate psoriasis by activating plasmacytoid dendritic cells or T cells,as demonstrated in in vitro experiments. However,in vitro experiments also have shown that visfatin may inhibit cardiomyocyte apoptosis.
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10.
Adipocytokine Involvement in Innate Immune Mechanisms.
Żelechowska, P, Kozłowska, E, Pastwińska, J, Agier, J, Brzezińska-Błaszczyk, E
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research. 2018;(12):527-538
Abstract
The innate immune response is defined as an immensely complex and sophisticated process aimed at defending the organism against any disturbance in the body homeostasis, including invading pathogens. It requires a close cooperation of a vast amount of different cell types, recognized as inflammatory migrating cells, as well as stationary cells that form tissues. Moreover, innate immune mechanisms require an efficient functioning of various humoral components that exert a significant impact on physiological and pathological processes. Apart from commonly mentioned humoral factors, this group also includes a family of proteins known as adipocytokines that may act as pro- or anti-inflammatory agents or act both ways. Leptin, predominantly characterized as a proinflammatory adipokine, plays a crucial role in endothelium remodeling and regulation, as well as in cell survival and production of numerous cytokines. Adiponectin, similar to leptin, acts on the endothelial cells and the phagocytic properties of immune cells; however, it exerts an anti-inflammatory impact. Resistin has a documented role in the control of angiogenesis and stimulation of proinflammatory mediator generation and release. Furthermore, there are adipokines, ie, visfatin and chemerin, whose participation in the inflammatory processes is ambiguous. This review focuses on the current knowledge on the extensive role of selected adipokines in innate immune response.