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Antioxidants & Redox Signaling Aug 2019Alterations in adipose tissue function have profound consequences on whole body energy homeostasis because this tissue is central for fat accumulation, energy... (Review)
Review
Alterations in adipose tissue function have profound consequences on whole body energy homeostasis because this tissue is central for fat accumulation, energy expenditure, glucose and insulin metabolism, and hormonal regulation. With the obesity reaching epidemic proportions globally, it is important to understand the mechanisms leading to adipose tissue malfunction. Autophagy has originally been viewed as an adaptive response to cellular stress, but in recent years this process was shown to regulate important cellular processes. In adipose tissue, autophagy is a key regulator of white adipose tissue (WAT) and brown adipose tissue (BAT) adipogenesis, and dysregulated autophagy impairs fat accumulation both and Animal studies have also suggested an important role for autophagy and mitophagy during the transition from beige to white fat. Human studies have provided evidence for altered autophagy in WAT, and these alterations correlated with the degree of insulin resistance. Despite these important advances in the study of autophagy in adipose tissue, we still do not understand the physiological role of autophagy in mature white and brown adipocytes. Furthermore, several human studies involving autophagy assessment were performed on whole adipose tissue, which complicates the interpretation of the results considering the cellular heterogeneity of this tissue. Future studies will undoubtedly expand our understanding of the role of autophagy in fully differentiated adipocytes, and uncover novel cross-talks between this tissue and other organs in regulating lipid metabolism, redox signaling, energy homeostasis, and insulin sensitivity.
Topics: Adipose Tissue; Animals; Autophagy; Humans
PubMed: 30234364
DOI: 10.1089/ars.2018.7626 -
Journal of Obesity 2022. Obesity is a global health problem of epidemic proportions, which is characterized by increased adipose tissue (AT) mass and significant repercussions in different... (Review)
Review
. Obesity is a global health problem of epidemic proportions, which is characterized by increased adipose tissue (AT) mass and significant repercussions in different body apparati and systems. AT is a special connective tissue, which contains several types of cells, in addition to adipocytes, and is a highly active endocrine and immune organ, which directly modulates many processes, including energy balance, metabolism, and inflammation. . In this paper, the authors list and attempt to answer in a brief and simple way several questions regarding the complex relationships between obesity, adipose tissue, and inflammation, with the objective to provide an easy way to understand the main changes that occur in this pathological state. The questions are the following: Is adipose tissue only made up of adipocytes? Are adipocytes just a reservoir of free fatty acids? Do different types of fatty tissue exist? If so, which types? Can we further subcategorize the types of adipose tissue? Is it possible to form new adipocytes during adulthood? What is the role of inflammation? What is the role of macrophages? Are macrophages central mediators of obesity-induced adipose tissue inflammation and insulin resistance? What causes macrophage infiltration into adipose tissue? What is the role of hypoxia in AT alterations? Is there cross talk between adipocytes and immune cells? What other changes occur in AT in obesity? Does metabolically healthy obesity really exist? Is this a benign condition? . Obesity is a complex disease with numerous metabolic consequences, which are mainly the result of dysfunction that occurs in the adipose tissue of patients with this pathology. Understanding the pathophysiology of AT and the changes that occur in obesity would contribute to a better approach to patients with obesity, with the inherent medical implications that could result from this.
Topics: Adipocytes; Adipose Tissue; Adult; Humans; Inflammation; Insulin Resistance; Obesity
PubMed: 35321537
DOI: 10.1155/2022/2252516 -
Nutrients Jul 2022Adipose tissue is the largest and most active endocrine organ, involved in regulating energy balance, glucose and lipid homeostasis and immune function. Adipose tissue... (Review)
Review
Adipose tissue is the largest and most active endocrine organ, involved in regulating energy balance, glucose and lipid homeostasis and immune function. Adipose tissue aging processes are associated with brown adipose tissue whitening, white adipose tissue redistribution and ectopic deposition, resulting in an increase in age-related inflammatory factors, which then trigger a variety of metabolic syndromes, including diabetes and hyperlipidemia. Metabolic syndrome, in turn, is associated with increased inflammatory factors, all-cause mortality and cognitive impairment. There is a growing interest in the role of nutritional interventions in adipose tissue aging. Nowadays, research has confirmed that nutritional interventions, involving caloric restriction and the use of vitamins, resveratrol and other active substances, are effective in managing adipose tissue aging's adverse effects, such as obesity. In this review we summarized age-related physiological characteristics of adipose tissue, and focused on what nutritional interventions can do in improving the retrogradation and how they do this.
Topics: Adipose Tissue; Adipose Tissue, Brown; Adipose Tissue, White; Aging; Caloric Restriction; Humans; Metabolic Diseases; Metabolic Syndrome
PubMed: 35956309
DOI: 10.3390/nu14153134 -
Mechanisms of Ageing and Development Oct 2021Age associated chronic inflammation is a major contributor to diseases with advancing age. Adipose tissue function is at the nexus of processes contributing to... (Review)
Review
Age associated chronic inflammation is a major contributor to diseases with advancing age. Adipose tissue function is at the nexus of processes contributing to age-related metabolic disease and mediating longevity. Hormonal fluctuations in aging potentially regulate age-associated visceral adiposity and metabolic dysfunction. Visceral adiposity in aging is linked to aberrant adipogenesis, insulin resistance, lipotoxicity and altered adipokine secretion. Age-related inflammatory phenomena depict sex differences in macrophage polarization, changes in T and B cell numbers, and types of dendritic cells. Sex differences are also observed in adipose tissue remodeling and cellular senescence suggesting a role for sex steroid hormones in the regulation of the adipose tissue microenvironment. It is crucial to investigate sex differences in aging clinical outcomes to identify and better understand physiology in at-risk individuals. Early interventions aimed at targets involved in adipose tissue adipogenesis, remodeling and inflammation in aging could facilitate a profound impact on health span and overcome age-related functional decline.
Topics: Adipose Tissue; Aging; Body Fat Distribution; Cellular Senescence; Humans; Inflammation; Longevity; Metabolic Networks and Pathways
PubMed: 34474078
DOI: 10.1016/j.mad.2021.111563 -
Nutrients Sep 2023Brown and beige adipocytes are renowned for their unique ability to generate heat through a mechanism known as thermogenesis. This process can be induced by exposure to... (Review)
Review
Brown and beige adipocytes are renowned for their unique ability to generate heat through a mechanism known as thermogenesis. This process can be induced by exposure to cold, hormonal signals, drugs, and dietary factors. The activation of these thermogenic adipocytes holds promise for improving glucose metabolism, reducing fat accumulation, and enhancing insulin sensitivity. However, the translation of preclinical findings into effective clinical therapies poses challenges, warranting further research to identify the molecular mechanisms underlying the differentiation and function of brown and beige adipocytes. Consequently, research has focused on the development of drugs, such as mirabegron, ephedrine, and thyroid hormone, that mimic the effects of cold exposure to activate brown fat activity. Additionally, nutritional interventions have been explored as an alternative approach to minimize potential side effects. Brown fat and beige fat have emerged as promising targets for addressing nutritional imbalances, with the potential to develop strategies for mitigating the impact of metabolic diseases. Understanding the influence of nutritional factors on brown fat activity can facilitate the development of strategies to promote its activation and mitigate metabolic disorders.
Topics: Adipose Tissue, Brown; Nutritional Status; Adipocytes; Adipocytes, Beige; Adipose Tissue, Beige
PubMed: 37764855
DOI: 10.3390/nu15184072 -
Advanced Science (Weinheim,... Jun 2022Obesity and associated diseases, such as diabetes, have reached epidemic proportions globally. In this era of "diabesity", white adipose tissue (WAT) has become a target...
Obesity and associated diseases, such as diabetes, have reached epidemic proportions globally. In this era of "diabesity", white adipose tissue (WAT) has become a target of high interest for therapeutic strategies. To gain insights into mechanisms of adipose (patho-)physiology, researchers traditionally relied on animal models. Leveraging Organ-on-Chip technology, a microphysiological in vitro model of human WAT is introduced: a tailored microfluidic platform featuring vasculature-like perfusion that integrates 3D tissues comprising all major WAT-associated cellular components (mature adipocytes, organotypic endothelial barriers, stromovascular cells including adipose tissue macrophages) in an autologous manner and recapitulates pivotal WAT functions, such as energy storage and mobilization as well as endocrine and immunomodulatory activities. A precisely controllable bottom-up approach enables the generation of a multitude of replicates per donor circumventing inter-donor variability issues and paving the way for personalized medicine. Moreover, it allows to adjust the model's degree of complexity via a flexible mix-and-match approach. This WAT-on-Chip system constitutes the first human-based, autologous, and immunocompetent in vitro adipose tissue model that recapitulates almost full tissue heterogeneity and can become a powerful tool for human-relevant research in the field of metabolism and its associated diseases as well as for compound testing and personalized- and precision medicine applications.
Topics: Adipocytes, White; Adipose Tissue; Adipose Tissue, White; Animals; Humans; Microfluidics; Obesity
PubMed: 35466539
DOI: 10.1002/advs.202104451 -
American Journal of Physiology.... Jul 2021Adipose is a key tissue regulating energy homeostasis. In states of obesity, caloric intake exceeds energy expenditure, thereby accelerating lipid accumulation with... (Review)
Review
Adipose is a key tissue regulating energy homeostasis. In states of obesity, caloric intake exceeds energy expenditure, thereby accelerating lipid accumulation with ongoing extracellular matrix (ECM) remodeling. Excess deposition of lipids and expansion of adipocytes potentially decrease ECM flexibility with local hypoxia and inflammation. Hypoxia and chronic low-grade inflammation accelerate the development of adipose tissue fibrosis and related metabolic dysfunctions. Recent research investigated that some cytokines and proteins are functional in regulating energy homeostasis, meanwhile, are potential targets to fight against adipose tissue fibrosis and insulin resistance. In this review, we focused on the regulatory mechanisms and mediators in remodeling of adipose tissue fibrosis, along with their relevance to clinical manifestations.
Topics: Adipocytes; Adipose Tissue; Animals; Blood Glucose; Cytokines; Energy Metabolism; Extracellular Matrix; Fibrosis; Homeostasis; Humans; Inflammation; Lipid Metabolism; Metabolic Diseases; Mitochondria; Obesity
PubMed: 34056922
DOI: 10.1152/ajpendo.00558.2020 -
International Journal of Molecular... Jul 2019Obesity is considered to significantly increase the risk of the development of a vast range of metabolic diseases. However, adipogenesis is a complex physiological... (Review)
Review
Obesity is considered to significantly increase the risk of the development of a vast range of metabolic diseases. However, adipogenesis is a complex physiological process, necessary to sequester lipids effectively to avoid lipotoxicity in other tissues, like the liver, heart, muscle, essential for maintaining metabolic homeostasis and has a crucial role as a component of the innate immune system, far beyond than only being an inert mass of energy storage. In pathophysiological conditions, adipogenesis promotes a pro-inflammatory state, angiogenesis and the release of adipokines, which become dangerous to health. It results in a hypoxic state, causing oxidative stress and the synthesis and release of harmful free fatty acids. In this review, we try to explain the mechanisms occurring at the breaking point, at which adipogenesis leads to an uncontrolled lipotoxicity. This review highlights the types of adipose tissue and their functions, their way of storing lipids until a critical point, which is associated with hypoxia, inflammation, insulin resistance as well as lipodystrophy and adipogenesis modulation by Krüppel-like factors and miRNAs.
Topics: Adipocytes; Adipogenesis; Adipose Tissue; Animals; Disease Susceptibility; Energy Metabolism; Humans; Lipogenesis; Panniculitis
PubMed: 31357412
DOI: 10.3390/ijms20153657 -
Nutrients Oct 2019Adipose tissue is a highly metabolically-active tissue that senses and secretes hormonal and lipid mediators that facilitate adaptations to metabolic tissues. In recent... (Review)
Review
Adipose tissue is a highly metabolically-active tissue that senses and secretes hormonal and lipid mediators that facilitate adaptations to metabolic tissues. In recent years, the role of lipokines, which are lipid species predominantly secreted from adipose tissue that act as hormonal regulators in many metabolic tissues, has been an important area of research for obesity and diabetes. Previous studies have identified that these secreted lipids, including palmitoleate, 12,13-diHOME, and fatty acid-hydroxy-fatty acids (FAHFA) species, are important regulators of metabolism. Moreover, environmental factors that directly affect the secretion of lipokines such as diet, exercise, and exposure to cold temperatures constitute attractive therapeutic strategies, but the mechanisms that regulate lipokine stimulation have not been thoroughly reviewed. In this study, we will discuss the chemical characteristics of lipokines that position them as attractive targets for chronic disease treatment and prevention and the emerging roles of lipokines as regulators of inter-tissue communication. We will define the target tissues of lipokines, and explore the ability of lipokines to prevent or delay the onset and development of chronic diseases. Comprehensive understanding of the lipokine synthesis and lipokine-driven regulation of metabolic outcomes is instrumental for developing novel preventative and therapeutic strategies that harness adipose tissue-derived lipokines.
Topics: Adipose Tissue; Cold Temperature; Diet; Exercise; Humans; Lipid Metabolism
PubMed: 31614481
DOI: 10.3390/nu11102422 -
Immunity Sep 2020Over the past 10 years, the field of immunometabolism made great strides to unveil the crucial role of intracellular metabolism in regulating immune cell function.... (Review)
Review
Over the past 10 years, the field of immunometabolism made great strides to unveil the crucial role of intracellular metabolism in regulating immune cell function. Emerging insights into how systemic inflammation and metabolism influence each other provide a critical additional dimension on the organismal level. Here, we discuss the concept of systemic immunometabolism and review the current understanding of the communication circuits that underlie the reciprocal impact of systemic inflammation and metabolism across organs in inflammatory and infectious diseases, as well as how these mechanisms apply to homeostasis. We present current challenges of systemic immunometabolic research, and in this context, highlight opportunities and put forward ideas to effectively explore organismal physiological complexity in both health and disease.
Topics: Adipose Tissue; Energy Metabolism; Homeostasis; Humans; Immune System; Inflammation
PubMed: 32937151
DOI: 10.1016/j.immuni.2020.08.012