scholarly journals ER Stress and Lipid Metabolism in Adipocytes

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Beth S. Zha ◽  
Huiping Zhou
Keyword(s):  
Lipid Metabolism ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Metabolic Diseases ◽  
Cell Types ◽  
Β Cells ◽  
The Metabolic Syndrome ◽  
Chronic Activation

The role of endoplasmic reticulum (ER) stress is a rapidly emerging field of interest in the pathogenesis of metabolic diseases. Recent studies have shown that chronic activation of ER stress is closely linked to dysregulation of lipid metabolism in several metabolically important cells including hepatocytes, macrophages, β-cells, and adipocytes. Adipocytes are one of the major cell types involved in the pathogenesis of the metabolic syndrome. Recent advances in dissecting the cellular and molecular mechanisms involved in the regulation of adipogenesis and lipid metabolism indicate that activation of ER stress plays a central role in regulating adipocyte function. In this paper, we discuss the current understanding of the potential role of ER stress in lipid metabolism in adipocytes. In addition, we touch upon the interaction of ER stress and autophagy as well as inflammation. Inhibition of ER stress has the potential of decreasing the pathology in adipose tissue that is seen with energy overbalance.

MicroRNA regulation of mitochondrial and ER stress signaling pathways: implications for lipoprotein metabolism in metabolic syndrome

2014 ◽  
Vol 307 (9) ◽  
pp. E729-E737 ◽  
Author(s):  
Patricia Christian ◽  
Qiaozhu Su
Keyword(s):  
Metabolic Syndrome ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Acid Oxidation ◽  
Aberrant Expression ◽  
The Metabolic Syndrome ◽  
Mitochondrial Fatty Acid

The development of metabolic syndrome is closely associated with the deregulation of lipid metabolism. Emerging evidence has demonstrated that microRNAs (miRNAs) are intensively engaged in lipid and lipoprotein metabolism by regulating genes involved in control of intracellular lipid synthesis, mitochondrial fatty acid oxidation, and lipoprotein assembly. Mitochondrial dysfunction induced by altered miRNA expression has been proposed to be a contributing factor in the onset of metabolic diseases, while at the same time, aberrant expression of certain miRNAs is associated with the induction of endoplasmic reticulum (ER) stress induced by nutrient-surplus. These studies position miRNAs as a link between oxidative stress and ER stress, two cellular stress pathways that are deregulated in metabolic disease and are associated with very-low-density lipoprotein (VLDL) overproduction. Dyslipoproteinemia frequently accompanied with metabolic syndrome is initiated largely by the overproduction of VLDL and altered biogenesis of high-density lipoprotein (HDL). In this review, we highlight recent findings on the regulatory impact of miRNAs on the metabolic homeostasis of mitochondria and ER as well as their contribution to the aberrant biogenesis of both VLDL and HDL in the context of metabolic disorders, in an attempt to gain further insights into the molecular mechanisms of dyslipidemia in the metabolic syndrome.

Transcriptional Regulation of Metabolism

2006 ◽  
Vol 86 (2) ◽  
pp. 465-514 ◽  
Author(s):  
Béatrice Desvergne ◽  
Liliane Michalik ◽  
Walter Wahli
Keyword(s):  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Transcriptional Control ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Cholesterol Metabolism ◽  
Regulatory Pathways ◽  
Glucose And Lipid Metabolism ◽  
The Metabolic Syndrome

Our understanding of metabolism is undergoing a dramatic shift. Indeed, the efforts made towards elucidating the mechanisms controlling the major regulatory pathways are now being rewarded. At the molecular level, the crucial role of transcription factors is particularly well-illustrated by the link between alterations of their functions and the occurrence of major metabolic diseases. In addition, the possibility of manipulating the ligand-dependent activity of some of these transcription factors makes them attractive as therapeutic targets. The aim of this review is to summarize recent knowledge on the transcriptional control of metabolic homeostasis. We first review data on the transcriptional regulation of the intermediary metabolism, i.e., glucose, amino acid, lipid, and cholesterol metabolism. Then, we analyze how transcription factors integrate signals from various pathways to ensure homeostasis. One example of this coordination is the daily adaptation to the circadian fasting and feeding rhythm. This section also discusses the dysregulations causing the metabolic syndrome, which reveals the intricate nature of glucose and lipid metabolism and the role of the transcription factor PPARγ in orchestrating this association. Finally, we discuss the molecular mechanisms underlying metabolic regulations, which provide new opportunities for treating complex metabolic disorders.

scholarly journals Exendin-4 inhibits glucolipotoxic ER stress in pancreatic β cells via regulation of SREBP1c and C/EBPβ transcription factors

2012 ◽  
Vol 216 (3) ◽  
pp. 343-352 ◽  
Author(s):  
Yoon Sin Oh ◽  
Youn-Jung Lee ◽  
Yup Kang ◽  
Jaeseok Han ◽  
Oh-Kyung Lim ◽  
...  
Keyword(s):  
Er Stress ◽  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Prolonged Exposure ◽  
Nuclear Translocation ◽  
Β Cells ◽  
Β Cell ◽  
Stress Markers ◽  
Glucagon Like Peptide 1

Prolonged exposure to high glucose (HG) and palmitate (PA) results in increased ER stress and subsequently induces β-cell apoptosis. Exendin-4, a glucagon-like peptide-1 agonist, is known to protect β cells from toxicity induced by cytokines, HG, or fatty acids by reducing ER stress. However, the detailed molecular mechanisms for this protective effect are still not known. In this study, we investigated the role of exendin-4 in the inhibition of glucolipotoxicity-induced ER stress and β-cell apoptosis. Exendin-4 treatment protected INS-1 β cells from apoptosis in response to HG/PA (25 mM glucose+400 μM PA). HG/PA treatment increased cleaved caspase-3 and induced ER stress maker proteins such as PERK (EIF2AK3), ATF6, and phosphorylated forms of PERK, eIF2α, IRE1α (ERN1), and JNK (MAPK8), and these increases were significantly inhibited by exendin-4 treatment. HG/PA treatment of INS-1 cells increased SREBP1 (SREBF1) protein and induced its nuclear translocation and subsequently increased C/EBPβ (CEBPB) protein and its nuclear translocation. Exendin-4 treatment attenuated this increase. Knockdown ofSREBP1creduced the activation ofC/EBPβand also blocked the expression of ER stress markers induced by HG/PA treatment. Our results indicate that exendin-4 inhibits the activation of SREBP1c and C/EBPβ, which, in turn, may reduce glucolipotoxicity-induced ER stress and β-cell apoptosis.

scholarly journals CCAAT/Enhancer Binding Proteinβin relation to ER Stress, Inflammation, and Metabolic Disturbances

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Sophie E. van der Krieken ◽  
Herman E. Popeijus ◽  
Ronald P. Mensink ◽  
Jogchum Plat
Keyword(s):  
Er Stress ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Developed Countries ◽  
Metabolic Disturbances ◽  
Metabolic System ◽  
Physiological Level ◽  
The Metabolic Syndrome ◽  
Brown Adipose

The prevalence of the metabolic syndrome and underlying metabolic disturbances increase rapidly in developed countries. Various molecular targets are currently under investigation to unravel the molecular mechanisms that cause these disturbances. This is done in attempt to counter or prevent the negative health consequences of the metabolic disturbances. Here, we reviewed the current knowledge on the role of C/EBP-βin these metabolic disturbances. C/EBP-βdeletion in mice resulted in downregulation of hepatic lipogenic genes and increased expression ofβ-oxidation genes in brown adipose tissue. Furthermore, C/EBP-βis important in the differentiation and maturation of adipocytes and is increased during ER stress and proinflammatory conditions. So far, studies were only conducted in animals and in cell systems. The results found that C/EBP-βis an important transcription factor within the metabolic disturbances of the metabolic system. Therefore, it is interesting to examine the potential role of C/EBP-βat molecular and physiological level in humans.

scholarly journals Regulation of Insulin Secretion and β-Cell Mass by Activating Signal Cointegrator 2

2006 ◽  
Vol 26 (12) ◽  
pp. 4553-4563 ◽  
Author(s):  
Seon-Yong Yeom ◽  
Geun Hyang Kim ◽  
Chan Hee Kim ◽  
Heun Don Jung ◽  
So-Yeon Kim ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Endocrine Cells ◽  
Potential Role ◽  
Cell Mass ◽  
Dominant Negative ◽  
Transcriptional Coactivator ◽  
Β Cells ◽  
Β Cell ◽  
Islet Mass

ABSTRACT Activating signal cointegrator 2 (ASC-2) is a transcriptional coactivator of many nuclear receptors (NRs) and other transcription factors and contains two NR-interacting LXXLL motifs (NR boxes). In the pancreas, ASC-2 is expressed only in the endocrine cells of the islets of Langerhans, but not in the exocrine cells. Thus, we examined the potential role of ASC-2 in insulin secretion from pancreatic β-cells. Overexpressed ASC-2 increased glucose-elicited insulin secretion, whereas insulin secretion was decreased in islets from ASC-2+/− mice. DN1 and DN2 are two dominant-negative fragments of ASC-2 that contain NR boxes 1 and 2, respectively, and block the interactions of cognate NRs with the endogenous ASC-2. Primary rat islets ectopically expressing DN1 or DN2 exhibited decreased insulin secretion. Furthermore, relative to the wild type, ASC-2+/− mice showed reduced islet mass and number, which correlated with increased apoptosis and decreased proliferation of ASC-2+/− islets. These results suggest that ASC-2 regulates insulin secretion and β-cell survival and that the regulatory role of ASC-2 in insulin secretion appears to involve, at least in part, its interaction with NRs via its two NR boxes.

scholarly journals Ayurveda Internal Medicine for the Management of Common Metabolic Disorders W.S.R. to Madhumeha and Sthoulya

2019 ◽  
Vol 9 (5-s) ◽  
pp. 167-169
Author(s):  
Dhananjay S. Khot
Keyword(s):  
Internal Medicine ◽  
Metabolic Syndrome ◽  
Life Style ◽  
Metabolic Disorders ◽  
Dietary Habits ◽  
Metabolic Diseases ◽  
Health Issues ◽  
The Metabolic Syndrome ◽  
Sedentary Life Style

The metabolic disorders are major health issues of today’s scenario and incidences of metabolic diseases increases day by day due to the disturbed pattern of life style. Ayurveda texts have described term “Santarpanjanya Vikaras” which resembles diseases of defective tissue metabolism. Ayurveda mentioned that improper dietary habits and sedentary life style affects state of Agni which resulted Ama production and finally leading to the metabolic syndrome. The vitiation of Dosha, diminish state of Dhatu and blockage of channels, etc. also can initiate pathogenesis of metabolic disorders. The Kayachikitsa branch of Ayurveda recommended use of internal medicine for the management of various metabolic disorders. Considering increased health burden of society due to the metabolic syndrome present article explore role of ayurveda internal medicine for the management of metabolic syndrome. Keywords: Ayurveda, metabolic syndrome, Santarpanjanya, Madhumeha and Sthoulya.       

scholarly journals RHBDL4 protects against endoplasmic reticulum stress by regulating the morphology and distribution of ER sheets

2021 ◽  
Author(s):  
Viorica Liebe Lastun ◽  
Matthew Freeman
Keyword(s):  
Cell Cycle ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Liver Steatosis ◽  
Physiological Role ◽  
Cell Types ◽  
Rhomboid Protease ◽  
Rapid Changes

In metazoans, the architecture of the endoplasmic reticulum (ER) differs between cell types, and undergoes major changes through the cell cycle and according to physiological needs. Although much is known about how the different ER morphologies are generated and maintained, especially the ER tubules, how context dependent changes in ER shape and distribution are regulated and the factors involved are less characterized. Here, we show that RHBDL4, an ER-resident rhomboid protease, modulates the shape and distribution of the ER, especially under conditions that require rapid changes in the ER sheet distribution, including ER stress. RHBDL4 interacts with CLIMP-63, a protein involved in ER sheet stabilisation, and with the cytoskeleton. Mice lacking RHBDL4 are sensitive to ER stress and develop liver steatosis, a phenotype associated with unresolved ER stress. Our data introduce a new physiological role of RHBDL4 and also imply that this function does not require its enzymatic activity.

scholarly journals Neuroinflammation and Its Impact on the Pathogenesis of COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Mohammed M. Almutairi ◽  
Farzane Sivandzade ◽  
Thamer H. Albekairi ◽  
Faleh Alqahtani ◽  
Luca Cucullo
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Immune Cell ◽  
Clinical Manifestations ◽  
Cell Infiltration ◽  
Cellular Mechanisms ◽  
Cytokine Levels

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical manifestations of COVID-19 include dry cough, difficult breathing, fever, fatigue, and may lead to pneumonia and respiratory failure. There are significant gaps in the current understanding of whether SARS-CoV-2 attacks the CNS directly or through activation of the peripheral immune system and immune cell infiltration. Although the modality of neurological impairments associated with COVID-19 has not been thoroughly investigated, the latest studies have observed that SARS-CoV-2 induces neuroinflammation and may have severe long-term consequences. Here we review the literature on possible cellular and molecular mechanisms of SARS-CoV-2 induced-neuroinflammation. Activation of the innate immune system is associated with increased cytokine levels, chemokines, and free radicals in the SARS-CoV-2-induced pathogenic response at the blood-brain barrier (BBB). BBB disruption allows immune/inflammatory cell infiltration into the CNS activating immune resident cells (such as microglia and astrocytes). This review highlights the molecular and cellular mechanisms involved in COVID-19-induced neuroinflammation, which may lead to neuronal death. A better understanding of these mechanisms will help gain substantial knowledge about the potential role of SARS-CoV-2 in neurological changes and plan possible therapeutic intervention strategies.

scholarly journals Pancreatic α and β cells are globally phase-locked

2020 ◽  
Author(s):  
Huixia Ren ◽  
Yanjun Li ◽  
Chengsheng Han ◽  
Yi Yu ◽  
Bowen Shi ◽  
...  
Keyword(s):  
Islet Cells ◽  
Cell Types ◽  
Phase Oscillators ◽  
Β Cells ◽  
Oscillation Modes ◽  
Different Types ◽  
Glucagon And Insulin ◽  
Different Cell Types

ABSTRACTThe Ca2+ modulated pulsatile secretions of glucagon and insulin by pancreatic α and β cells play a key role in glucose metabolism and homeostasis. However, how different types of islet cells couple and coordinate via paracrine interactions to produce various Ca2+ oscillation patterns are still elusive. By designing a microfluidic device to facilitate long-term recording of islet Ca2+ activity at single cell level and simultaneously identifying different cell types in live islet imaging, we show heterogeneous but intrinsic Ca2+ oscillation patterns of islets upon glucose stimulation. The α and β cells oscillate in antiphase and are globally phase locked to various phase delays, causing fast, slow or mixed oscillations. A mathematical model of coupled phase oscillators quantitatively agrees with experiments and reveals the essential role of paracrine regulations in tuning the oscillation modes. Our study highlights the importance of cell-cell interactions to generate stable but tunable islet oscillation patterns.

scholarly journals ER stress and development of type 1 diabetes

2016 ◽  
Vol 64 (1) ◽  
pp. 2-6 ◽  
Author(s):  
Feyza Engin
Keyword(s):  
Type 1 Diabetes ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Adaptive Responses ◽  
Β Cell ◽  
Cellular Homeostasis ◽  
Unfolded Protein

Type 1 diabetes (T1D) results from an autoimmune-mediated destruction of pancreatic β cells. The incidence of T1D is on the rise globally around 3% to 5% per year and rapidly increasing incidence in younger children is of the greatest concern. currently, there is no way to cure or prevent T1D; hence, a deeper understanding of the underlying molecular mechanisms of this disease is essential to the development of new effective therapies. The endoplasmic reticulum (ER) is an organelle with multiple functions that are essential for cellular homeostasis. Excessive demand on the ER, chronic inflammation, and environmental factors lead to ER stress and to re-establish cellular homeostasis, the adaptive unfolded protein response (UPR) is triggered. However, chronic ER stress leads to a switch from a prosurvival to a proapoptotic UPR, resulting in cell death. Accumulating data have implicated ER stress and defective UPR in the pathogenesis of inflammatory and autoimmune diseases, and ER stress has been implicated in β-cell failure in type 2 diabetes. However, the role of ER stress and the UPR in β-cell pathophysiology and in the initiation and propagation of the autoimmune responses in T1D remains undefined. This review will highlight the current understanding and recent in vivo data on the role of ER stress and adaptive responses in T1D pathogenesis and the potential therapeutic aspect of enhancing β-cell ER function and restoring UPR defects as novel clinical strategies against this disease.

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