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Cellular Stress Response in Metabolic Syndrome

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 4557

Special Issue Editor


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Guest Editor
Department of Pharmacology, New Drug Development Institute, Chonbuk National University, Jeonju, Republic of Korea
Interests: ER stress; cellular stress; signaling pathways; autophagy; chaperone; apoptosis; mitochondria metabolism; functional Foods; inflammation; nutraceuticals; glucose metabolism; mTOR; PI3K

Special Issue Information

Dear Colleagues,

The trajectory of metabolic syndrome is determined by how cells respond to specific stress factors. These stress factors influence the form of response (adaptive/non-adaptive) to various pathological conditions, including diabetes, hepatic dysmetabolism, pancreatic disorder, and obesity. However, metabolic plasticity is largely driven by signaling networks that tune the cellular response. For instance, components of ER stress axis, such as IRE-α, PERK, ATF6, and ER-juxtaposed mitochondrial signaling, are emerging crucial hubs for autophagy, apoptosis, and energy metabolism with far-reaching implications on metabolic syndrome. ER and mitochondria are well-received key players in metabolism and are regulated by several molecular mechanisms. Therefore, regulators of ER stress and its associated metabolic stress could be targets for developing therapies against metabolic syndrome. However, the path to remedy is not possible without an in-depth understanding of molecular cues on cellular stress response in metabolic syndrome. Thus, this Special Issue aims to aggregate current breakthroughs and emerging novel concepts that drive a better understanding of metabolic syndrome, which could be applied to optimize cellular responses in order to treat metabolic syndrome.

Prof. Dr. Han-Jung Chae
Guest Editor

Manuscript Submission Information

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Keywords

  • metabolic syndrome
  • metabolic plasticity
  • cell response
  • stress factors
  • signaling networks
  • ER stress
  • mitochondrial signaling

Published Papers (3 papers)

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Research

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12 pages, 1018 KiB  
Article
Interaction of Orexin and Bone Morphogenetic Proteins in Steroidogenesis by Human Adrenocortical Cells
by Yoshiaki Soejima, Nahoko Iwata, Ran Nishioka, Mako Honda, Yasuhiro Nakano, Koichiro Yamamoto, Atsuhito Suyama and Fumio Otsuka
Int. J. Mol. Sci. 2023, 24(16), 12559; https://doi.org/10.3390/ijms241612559 - 08 Aug 2023
Cited by 2 | Viewed by 1023
Abstract
Orexins are neuropeptides that play important roles in sleep-wake regulation and food intake in the central nervous system, but their receptors are also expressed in peripheral tissues, including the endocrine system. In the present study, we investigated the functions of orexin in adrenal [...] Read more.
Orexins are neuropeptides that play important roles in sleep-wake regulation and food intake in the central nervous system, but their receptors are also expressed in peripheral tissues, including the endocrine system. In the present study, we investigated the functions of orexin in adrenal steroidogenesis using human adrenocortical H295R cells by focusing on its interaction with adrenocortical bone morphogenetic proteins (BMPs) that induce adrenocortical steroidogenesis. Treatment with orexin A increased the mRNA levels of steroidogenic enzymes including StAR, CYP11B2, CYP17, and HSD3B1, and these effects of orexin A were further enhanced in the presence of forskolin. Interestingly, orexin A treatment suppressed the BMP-receptor signaling detected by Smad1/5/9 phosphorylation and Id-1 expression through upregulation of inhibitory Smad7. Orexin A also suppressed endogenous BMP-6 expression but increased the expression of the type-II receptor of ActRII in H295R cells. Moreover, treatment with BMP-6 downregulated the mRNA level of OX1R, but not that of OX2R, expressed in H295R cells. In conclusion, the results indicate that both orexin and BMP-6 accelerate adrenocortical steroidogenesis in human adrenocortical cells; both pathways mutually inhibit each other, thereby leading to a fine-tuning of adrenocortical steroidogenesis. Full article
(This article belongs to the Special Issue Cellular Stress Response in Metabolic Syndrome)
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Review

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14 pages, 1404 KiB  
Review
Key Genetic Components of Fibrosis in Diabetic Nephropathy: An Updated Systematic Review and Meta-Analysis
by Maria Tziastoudi, Theoharis C. Theoharides, Evdokia Nikolaou, Maria Efthymiadi, Theodoros Eleftheriadis and Ioannis Stefanidis
Int. J. Mol. Sci. 2022, 23(23), 15331; https://doi.org/10.3390/ijms232315331 - 05 Dec 2022
Cited by 8 | Viewed by 2140
Abstract
Renal fibrosis (RF) constitutes the common end-point of all kinds of chronic kidney disease (CKD), regardless of the initial cause of disease. The aim of the present study was to identify the key players of fibrosis in the context of diabetic nephropathy (DN). [...] Read more.
Renal fibrosis (RF) constitutes the common end-point of all kinds of chronic kidney disease (CKD), regardless of the initial cause of disease. The aim of the present study was to identify the key players of fibrosis in the context of diabetic nephropathy (DN). A systematic review and meta-analysis of all available genetic association studies regarding the genes that are included in signaling pathways related to RF were performed. The evaluated studies were published in English and they were included in PubMed and the GWAS Catalog. After an extensive literature review and search of the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, eight signaling pathways related to RF were selected and all available genetic association studies of these genes were meta-analyzed. ACE, AGT, EDN1, EPO, FLT4, GREM1, IL1B, IL6, IL10, IL12RB1, NOS3, TGFB1, IGF2/INS/TH cluster, and VEGFA were highlighted as the key genetic components driving the fibrosis process in DN. The present systematic review and meta-analysis indicate, as key players of fibrosis in DN, sixteen genes. However, the results should be interpreted with caution because the number of studies was relatively small. Full article
(This article belongs to the Special Issue Cellular Stress Response in Metabolic Syndrome)
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Other

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9 pages, 665 KiB  
Brief Report
Multi-Organ Increase in Norepinephrine Levels after Central Leptin Administration and Diet-Induced Obesity
by Daniela Fernandois, María Jesús Vázquez, Alexia Barroso, Alfonso H. Paredes, Manuel Tena-Sempere and Gonzalo Cruz
Int. J. Mol. Sci. 2023, 24(23), 16909; https://doi.org/10.3390/ijms242316909 - 29 Nov 2023
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Abstract
Autonomic innervation is important to regulate homeostasis in every organ of the body. The sympathetic nervous system controls several organs associated with metabolism and reproduction, including adipose tissue, the liver, and the ovaries. The sympathetic nervous system is controlled within the central nervous [...] Read more.
Autonomic innervation is important to regulate homeostasis in every organ of the body. The sympathetic nervous system controls several organs associated with metabolism and reproduction, including adipose tissue, the liver, and the ovaries. The sympathetic nervous system is controlled within the central nervous system by neurons located in the hypothalamus, which in turn are regulated by hormones like leptin. Leptin action in the hypothalamus leads to increased sympathetic activity in the adipose tissue. In this short report, we propose that leptin action in the brain also controls the sympathetic innervation of other organs like the liver and the ovary. We performed two experiments: We performed an intracerebroventricular (ICV) injection of leptin and measured norepinephrine levels in several organs, and we used a validated model of overnutrition and obesity to evaluate whether an increase in leptin levels coexists with high levels of norepinephrine in the liver and ovaries. Norepinephrine was measured by ELISA in adipose tissue and by HPLC-EC in other tissues. Leptin was measured by ELISA. We found that the ICV injection of leptin increases norepinephrine levels in several organs, including the liver and ovaries. Also, we found that diet-induced obesity leads to an increase in leptin levels while inducing an increase in norepinephrine levels in the liver and ovaries. Finally, since hyperactivity of the sympathetic nervous system is observed both in non-alcoholic fatty liver disease and polycystic ovary syndrome, we think that an increase in norepinephrine levels induced by hyperleptinemia could be involved in the pathogenesis of both diseases. Full article
(This article belongs to the Special Issue Cellular Stress Response in Metabolic Syndrome)
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