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  • GM dysbiosis and progression of

    2019-07-06

    GM dysbiosis and progression of diabetic nephropathy
    Conclusions
    Transparency document
    Introduction The prevalence of obesity is increasing worldwide and has become a major public health problem during the past decades [1]. Obesity has been recognized as a significant risk factor of cardiovascular diseases (CVD) and severe premature cardiac aging. The National Health and Nutrition Examination Survey (NHANES III, 1988–1994; NHANES continuous, 1999–2010) revealed reduced lifespan with increased body mass index (BMI) (reduce life expectancy at the age of 40 by 0.9 years), which was responsible for 186,000 excess deaths in 2011 [2]. More epidemiological studies confirm the tight association between obesity and reduced lifespan [[3], [4], [5], [6]]. Obesity is found closely related to premature cardiac aging and high-risk factor in young patients, contributing to an increased risk for 2-NBDG structure failure with aging [7]. Inflammation, oxidative stress, mitochondrial dysfunction and autophagy disorder caused by obesity generally accelerate the development of cardiac aging and heart diseases (as depicted in Fig. 1) [8]. As the increasing age, the heart trends to display an increased accumulation of lipid and decreased number of cardiomyocytes. Premature aging is commonly associated with the increasing prevalence of obesity, while both obesity and aging are comorbidities leading to severe CVD and increased risk 2-NBDG structure of death [8]. Both obesity and aging are tied with an increased risk for cardiac surgery, and thus, it is interesting to underline the contemporary mechanisms related with obesity-induced premature aging and associated cardiac dysfunction ultimately leading to heart failure [9]. Autophagy is the process by which cellular components are degraded and recycled within the cell. Increasing lines of evidence show that autophagy plays a crucial role in obesity and heart aging and during stress [10,11]. In obese patients, obesity disrupts autophagosome maturation probably at the step of autophagosome–lysosome fusion, although it promotes the initiation and accumulation of autophagy correlating with the degree of obesity [12]. Inhibition of autophagy in the heart induces premature cardiac aging which is generally accompanied by cardiac hypertrophy, fibrosis, accumulation of misfolded proteins and impaired mitochondrial function [13]. These findings raise the emerging possibility that autophagy may play an essential role in combating the adverse effects of obesity-related cardiac dysfunction. In this review, we discuss the role of autophagy in obesity-induced cardiac aging and diseases.
    Mechanisms of obesity-related cardiac aging Age-related CVDs are characterized by decreased contractility, impaired diastolic function, and atrium dilatation which is a rapidly increasing problem worldwide. During the aging process, both the morphological and functional alterations result in these diseases of the heart [21]. Obesity accelerates the aging process, and it is the key factor that risks premature severe cardiac aging and obesity-associated cardiac dysfunction [22]. It is reported that a large decrease in life expectancy and an increase in early mortality were associated with obesity [23]. With the age increases, obese patients are suffering from an increase in age-associated disease prevalence suggesting a premature aging phenotype [24]. The common features – such as impaired immunity, oxidative and inflammatory stress and mitochondrial dysfunction – have been revealed for both obesity and advanced aging [25]. Notably, adequate evidence indicates that the impaired or declined autophagy in the degradation system has a vital impact on senescence development with the cardiovascular system. Herein, we review the mechanisms of obesity-related cardiac disease.
    The intervention of obesity-related cardiac aging and heart diseases targeting autophagy
    Summary and conclusion There is an increasing need for the understanding of the correlation between obesity cardiac aging and CVD. Given that obesity includes a cluster of cardiovascular risk factors, it is not surprising that patients with obesity are more susceptible to cardiac aging and functional damage. Autophagy plays an important role in obesity, cardiac aging and heart diseases. In cardiomyocytes, accumulation of damaged proteins, DNA, and cellular organelles contributes to prematured aging process [69]. Autophagy has an essential role in the clearance of these damaged proteins and organelles which is crucial for the heart homeostasis in the aging process. Recently studies in mice model strongly supported that autophagy is a critical protective cardiac aging during obesity stress [77]. In obese patients, obesity disrupts autophagosome maturation probably at the step of autophagosome–lysosome fusion [10]. Inhibition of autophagy in the heart induces premature cardiac aging which is generally accompanied by cardiac hypertrophy, fibrosis, accumulation of misfolded proteins and impaired mitochondrial function [11]. Although management of cardiac aging and heart diseases with non-pharmacological regimens such as life style and dietary modification benefits organismal health, the application of pharmacotherapies targeting autophagy remains dismal for the obesity-related cardiac aging and heart disease discussed here in this mini-review [128]. A better understanding of the mechanisms involved in obesity-induced heart aging should help to guide the drug development for these metabolic anomalies.