Papers by Mariana Cifuentes
International Journal of Molecular Sciences, Mar 9, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
International Journal of Molecular Sciences
Adipose tissue inflammation in obesity has a deleterious impact on organs such as the liver, ulti... more Adipose tissue inflammation in obesity has a deleterious impact on organs such as the liver, ultimately leading to their dysfunction. We have previously shown that activation of the calcium-sensing receptor (CaSR) in pre-adipocytes induces TNF-α and IL-1β expression and secretion; however, it is unknown whether these factors promote hepatocyte alterations, particularly promoting cell senescence and/or mitochondrial dysfunction. We generated conditioned medium (CM) from the pre-adipocyte cell line SW872 treated with either vehicle (CMveh) or the CaSR activator cinacalcet 2 µM (CMcin), in the absence or presence of the CaSR inhibitor calhex 231 10 µM (CMcin+cal). HepG2 cells were cultured with these CM for 120 h and then assessed for cell senescence and mitochondrial dysfunction. CMcin-treated cells showed increased SA-β-GAL staining, which was absent in TNF-α- and IL-1β-depleted CM. Compared to CMveh, CMcin arrested cell cycle, increased IL-1β and CCL2 mRNA, and induced p16 and p53 s...
Revista chilena de nutrición
Efecto del extracto hidroalcohólico de la planta Lampaya medicinalis Phil. sobre marcadores infla... more Efecto del extracto hidroalcohólico de la planta Lampaya medicinalis Phil. sobre marcadores inflamación inducidos por ácidos grasos en hepatocitos humanos HepG2 Effect of the hydroalcoholic extract of the Lampaya medicinalis Phil. on fatty acid-induced inflammatory markers in human hepatocytes HepG2
International Journal of Molecular Sciences, 2020
Autophagy is upregulated in adipose tissue (AT) from people with obesity. We showed that activati... more Autophagy is upregulated in adipose tissue (AT) from people with obesity. We showed that activation of the calcium-sensing receptor (CaSR) elevates proinflammatory cytokines through autophagy in preadipocytes. Our aim is to understand the role of CaSR on autophagy in AT from humans with obesity. We determined mRNA and protein levels of CaSR and markers of autophagy by qPCR and western blot in human visceral AT explants or isolated primary preadipocytes (60 donors: 72% female, 23–56% body fat). We also investigated their association with donors’ anthropometric variables. Donors’ % body fat and CaSR mRNA expression in AT were correlated (r = 0.44, p < 0.01). CaSR expression was associated with mRNA levels of the autophagy markers atg5 (r = 0.37, p < 0.01), atg7 (r = 0.29, p < 0.05) and lc3b (r = 0.40, p < 0.01). CaSR activation increased becn and atg7 mRNA expression in AT. CaSR activation also upregulated LC3II by ~50%, an effect abolished by the CaSR inhibitor. Spermine ...
Journal of the Endocrine Society, 2020
Background: Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic chronic disease ... more Background: Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic chronic disease worldwide. NAFLD is characterized by an abnormal triglyceride (TG) accumulation (steatosis) in the liver, that may lead to hepatic inflammation (1). DGAT2 is a key enzyme that catalyzes the final step of TG synthesis and whose expression is elevated in NAFLD (2). FABP4 is a transporter of intracellular lipids and its levels are related with inflammation, characterized by a high expression of proinflammatory cytokines such as TNF-α, IL-6 and IL-1β. Palmitic acid (PA, C16:0) and oleic acid (OA; C18:1) are two of the most abundant fatty acids that participate in the formation of TGs in hepatic cells in vivo and in vitro (3). Lampaya medicinalis Phil. (Verbenaceae) is a small bush that grows in the “Puna atacameña” in the North of Chile. The infusion from leaves and aerial parts of the plant has been used by local ethnic groups to treat and cure inflammatory diseases (4). The aim of this stu...
Molecular and Cellular Endocrinology, 2019
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2018
© 2018 Elsevier B.V. Obesity is a major current public health problem worldwide due to the severe... more © 2018 Elsevier B.V. Obesity is a major current public health problem worldwide due to the severe co-morbid conditions that this disease entails. The development of obesity-related cardiometabolic disorders is in direct association with adipose tissue inflammation that leads to its functional impairment. Activation of the Calcium-Sensing Receptor (CaSR) in adipose tissue contributes to inflammation and adipose dysfunction. Autophagy, a process of cell component degradation, is closely related to inflammation in many diseases, however, whether autophagy is associated with CaSR-induced inflammation remains unknown. Using LS14 and SW872 preadipose cell lines as well as primary human preadipocytes, we show that CaSR activation with the allosteric activator cinacalcet induces autophagosome formation. Cinacalcet-induced LC3II content elevation was precluded by knockdown of the CaSR and enhanced by CaSR overexpression, indicating a specific effect. Autophagy inhibition using 3-methyladenine p
Pharmacological Research, 2019
Cell death and differentiation, Jan 12, 2018
Close contacts between endoplasmic reticulum and mitochondria enable reciprocal Ca exchange, a ke... more Close contacts between endoplasmic reticulum and mitochondria enable reciprocal Ca exchange, a key mechanism in the regulation of mitochondrial bioenergetics. During the early phase of endoplasmic reticulum stress, this inter-organellar communication increases as an adaptive mechanism to ensure cell survival. The signalling pathways governing this response, however, have not been characterized. Here we show that caveolin-1 localizes to the endoplasmic reticulum-mitochondria interface, where it impairs the remodelling of endoplasmic reticulum-mitochondria contacts, quenching Ca transfer and rendering mitochondrial bioenergetics unresponsive to endoplasmic reticulum stress. Protein kinase A, in contrast, promotes endoplasmic reticulum and mitochondria remodelling and communication during endoplasmic reticulum stress to promote organelle dynamics and Ca transfer as well as enhance mitochondrial bioenergetics during the adaptive response. Importantly, caveolin-1 expression reduces prote...
Journal of cellular physiology, 2018
The study of the mechanisms that trigger inflammation in adipose tissue is key to understanding a... more The study of the mechanisms that trigger inflammation in adipose tissue is key to understanding and preventing the cardiometabolic consequences of obesity. We have proposed a model where activation of the G protein-coupled calcium sensing receptor (CaSR) leads to inflammation and dysfunction in adipose cells. Upon activation, CaSR can mediate the expression and secretion of proinflammatory factors in human preadipocytes, adipocytes, and adipose tissue explants. One possible pathway involved in CaSR-induced inflammation is the activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome, that promotes maturation and secretion of interleukin (IL)-1β. The present work aimed to study whether CaSR mediates the activation of NLRP3 inflammasome in the human adipose cell model LS14. We assessed NLRP3 inflammasome priming and assembly after cinacalcet-induced CaSR activation and evaluated if this activation is mediated by downstream ERK1/2 signaling in LS14 preadipocytes. Exp...
Free radical biology & medicine, Jan 30, 2018
Non-communicable diseases (NCDs), also known as chronic diseases, are long-lasting conditions tha... more Non-communicable diseases (NCDs), also known as chronic diseases, are long-lasting conditions that affect millions of people around the world. Different factors contribute to their genesis and progression; however they share common features, which are critical for the development of novel therapeutic strategies. A persistently altered inflammatory response is typically observed in many NCDs together with redox imbalance. Additionally, dysregulated proteostasis, mainly derived as a consequence of compromised autophagy, is a common feature of several chronic diseases. In this review, we discuss the crosstalk among inflammation, autophagy and oxidative stress, and how they participate in the progression of chronic diseases such as cancer, cardiovascular diseases, obesity and type II diabetes mellitus.
Molecular, Genetic, and Nutritional Aspects of Major and Trace Minerals, 2017
Abstract As a major health problem worldwide, obesity is the focus of vast attention, and basic r... more Abstract As a major health problem worldwide, obesity is the focus of vast attention, and basic research has a key role in understanding the mechanisms leading to its deleterious health consequences. Studies in the past 15 years have addressed the hypothesis that deficient dietary calcium is associated with obesity and cardiometabolic risk. Among the mechanisms described in the pathophysiology of obesity and its comorbidities, calcium may be an overlooked relevant extracellular and intracellular factor. Emerging research also suggests that the calcium-sensing receptor is a promising mediator for many of the mechanisms linking calcium, obesity, and comorbidities. In this chapter, we discuss the calcium and obesity hypothesis and provide evidence supporting a role for the calcium-sensing receptor in obesity and its related diseases, the basics of cellular calcium handling, and processes in which this mineral regulates adipocyte function and pathogenesis.
Frontiers in Physiology, 2016
Obesity is currently a serious worldwide public health problem, reaching pandemic levels. For dec... more Obesity is currently a serious worldwide public health problem, reaching pandemic levels. For decades, dietary and behavioral approaches have failed to prevent this disease from expanding, and health authorities are challenged by the elevated prevalence of co-morbid conditions. Understanding how obesity-associated diseases develop from a basic science approach is recognized as an urgent task to face this growing problem. White adipose tissue (WAT) is an active endocrine organ, with a crucial influence on whole-body homeostasis. WAT dysfunction plays a key role linking obesity with its associated diseases such as type 2 diabetes mellitus, cardiovascular disease, and some cancers. Among the regulators of WAT physiology, the calcium-sensing receptor (CaSR) has arisen as a potential mediator of WAT dysfunction. Expression of the receptor has been described in human preadipocytes, adipocytes, and the human adipose cell lines LS14 and SW872. The evidence suggests that CaSR activation in the visceral (i.e., unhealthy) WAT is associated with an increased proliferation of adipose progenitor cells and elevated adipocyte differentiation. In addition, exposure of adipose cells to CaSR activators in vitro elevates proinflammatory cytokine expression and secretion. An increased proinflammatory environment in WAT plays a key role in the development of WAT dysfunction that leads to peripheral organ fat deposition and insulin resistance, among other consequences. We propose that CaSR may be one relevant therapeutic target in the struggle to confront the health consequences of the current worldwide obesity pandemic.
American Journal of Physiology-Endocrinology and Metabolism, 2016
Calcium signaling plays a crucial role in a multitude of events within the cardiomyocyte, includi... more Calcium signaling plays a crucial role in a multitude of events within the cardiomyocyte, including cell cycle control, growth, apoptosis, and autophagy. With respect to calcium-dependent regulation of autophagy, ion channels and exchangers, receptors, and intracellular mediators play fundamental roles. In this review, we discuss calcium-dependent regulation of cardiomyocyte autophagy, a lysosomal mechanism that is often cytoprotective, serving to defend against disease-related stress and nutrient insufficiency. We also highlight the importance of the subcellular distribution of calcium and related proteins, interorganelle communication, and other key signaling events that govern cardiomyocyte autophagy.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2015
Eukaryotic cells contain a variety of subcellular organelles, each of which performs unique tasks... more Eukaryotic cells contain a variety of subcellular organelles, each of which performs unique tasks. Thus follows that in order to coordinate these different intracellular functions, a highly dynamic system of communication must exist between the various compartments. Direct endoplasmic reticulum (ER)-mitochondria communication is facilitated by the physical interaction of their membranes in dedicated structural domains known as mitochondria-associated membranes (MAMs), which facilitate calcium (Ca 2+) and lipid transfer between organelles and also act as platforms for signaling. Numerous studies have demonstrated the importance of MAM in ensuring correct function of both organelles, and recently MAMs have been implicated in the genesis of various human diseases. Here, we review the salient structural features of interorganellar communication via MAM and discuss the most common experimental techniques employed to assess functionality of these domains. Finally, we will highlight the contribution of MAM to a variety of cellular functions and consider the potential role of MAM in the genesis of metabolic diseases. In doing so, the importance for cell functions of maintaining appropriate communication between ER and mitochondria will be emphasized.
Nutrition and Bone Health, 2004
Endocrine Abstracts, 2015
Nicolas Crisosto DOI: 10.3252/pso.eu.17ece.2015 Reproduction, endocrine disruptors and signalling... more Nicolas Crisosto DOI: 10.3252/pso.eu.17ece.2015 Reproduction, endocrine disruptors and signalling (1)Laboratory of Endocrinology and Metabolism, Faculty of Medicine, West Division, University of Chile (2) Laboratory of Nutritional Genomics, Department of Nutrition, Faculty of Medicine, University of Chile.(3) Basic Nutrition and Genetic Epidemiology Laboratory Institute of Nutrition and Food Technology (INTA), University of Chile. (4) Surgery Unit, Hospital San Juan de Dios, (5) Surgery Unit, Clinica Las Condes. FONDECYT Iniciacion 11130126 FONDECYT 1110864
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Papers by Mariana Cifuentes