Mechanism of ER Stress and Inflammation for Hepatic Insulin Resistance in Obesity

Kim, Ok‐Kyung; Jun, Woojin; Lee, Jeongmin

doi:10.1159/000440905

Cited by 84 publications

(62 citation statements)

References 75 publications

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“…Moreover, experimental studies link AAP exposure and endoplasmic reticulum (ER) stress-induced apoptosis in the lung and liver tissue along with brown adipose tissue dysfunction (62)(63)(64). ER stress enables the unfolded protein response (UPR) which contributes to the development of IR via inflammation, lipid accumulation, insulin biosynthesis and β-cell apoptosis (65)(66)(67)(68). Thus, the accumulative experimental and epidemiological evidence strongly suggest a biological association between AAP and IR.…”

Section: Discussionmentioning

confidence: 99%

Outdoor Air Pollution and Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis

Elshahidi

2019

ijph

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Background: During the past 20 years, the prevalence of gestational diabetes mellitus (GDM) has increased by ∼10%-100% in several race/ethnicity groups. There is an association between ambient air pollution (AAP) and GDM. This study aimed to summarize the evidence about the association between AAP and GDM. Methods: PubMed, Embase, Scopus, Web of Science and Cochrane Library were searched from inception till Oct 2017. Studies about the association between ambient air pollutants levels and GDM were included. Pooled effect estimates and their 95% confidence interval (CI) were calculated using R. Results: Eight studies met the inclusion criteria. The odds of developing GDM upon exposure to CO (per 1 ppm), NO (per 1 ppb), NO2 (per 10 µg/m3), NOx (per 1 ppb), O3 (per 10 ppb), SO2 (per 10 ppb), PM10 (per 10 µg/m3) and PM2.5 (per 10 µg/m3) were 1.47 (95% CI 0.88-2.06), 1.04 (95% CI 1.03-1.06), 1 (95% CI 0.93-1.08), 1.02 (95% CI 1-1.04), 1.05 (95% CI 0.94-1.16), 1.39 (95% CI 1.04-1.73), 0.97 (95% CI 0.94-0.99) and 1.12 (95% CI 0.93-1.31), respectively. Conclusion: The current literature showed evidence for an association between AAP and GDM. However, further well-designed studies are needed.

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Section: Discussionmentioning

confidence: 99%

Outdoor Air Pollution and Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis

Elshahidi

2019

ijph

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“…When ER stress was induced by excessive SFAs, cholesterol, and misfolded proteins, UPR was triggered through activation of 3 pathways, controlled by IRE1a, PRK-like ER kinase (PERK), and transcription factor-6 (ATF6), to initiate an adaptive program [34]. However, if ER homeostasis is not restored by activating UPR recovery pathways, improper responses to ER stress will result in lipid disorder, inflammation, oxidative stress, and apoptosis, which may create a lipotoxic environment upon NAFLD [35][36][37]. It has been well known that chronic ER stress led to inflammation via activating the IRE1a signal pathway.…”

Section: Discussionmentioning

confidence: 99%

Plant Sterol Ester of α-Linolenic Acid Attenuates Nonalcoholic Fatty Liver Disease by Rescuing the Adaption to Endoplasmic Reticulum Stress and Enhancing Mitochondrial Biogenesis

Han

Guo

et al. 2019

Oxidative Medicine and Cellular Longevity

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Nonalcoholic fatty liver disease (NAFLD) is becoming more common in the world and is presenting a great challenge concerning prevention and treatment. Plant sterol ester of α-linolenic acid (PS-ALA) has a potential benefit to NAFLD. To examine the effect of PS-ALA on NAFLD, C57BL/6J mice were given a control diet, high fat and high cholesterol diet (HFD), and HFD plus 2% PS, 1.3% ALA, or 3.3% PS-ALA for 16 weeks. Our results showed that PS-ALA treatment suppressed hepatic steatosis, ameliorated lipid disorder, attenuated inflammatory response, and inhibited oxidative stress. In the molecular level, PS-ALA downregulated high transcriptional and translational levels of endoplasmic reticulum (ER) stress markers (Grp78 and Chop) leading to decreased protein expression of transcription factor and key enzymes involved in de novo lipogenesis (Srebp-1c and Fas) and cholesterol synthesis (Srebp-2 and Hmgcr). In parallel, PS-ALA blocked Nlrp3 activation and reduced release of IL-1β and IL-18 via inhibiting ER stress-induced sensitization of unfolded protein response sensors (Ire1α and Xbp1s). Finally, PS-ALA improved HFD-induced mitochondrial damage and fatty acid accumulation as exhibited by higher protein and mRNA expression of key genes administering mitochondrial biogenesis (Pgc-1α, Nrf1, and Tfam) and fatty acid β-oxidation (Pparα and Cpt1a). In conclusion, our study originally demonstrated that PS-ALA rescued ER stress, enhanced mitochondrial biogenesis, and thus ameliorated NAFLD.

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“…A recent study has linked ER stress to inflammatory responses elicited by steatotic hepatocytes through the release of proinflammatory extracellular vesicles (EVs) . ER stress has been implicated in obesity‐associated IR and also in inflammation in various models . The contribution of ER stress to inflammation in NASH needs further exploration.…”

Section: Steatosis and Lipotoxicitymentioning

confidence: 99%

“…(44) ER stress has been implicated in obesity-associated IR and also in inflammation in various models. (45) The contribution of ER stress to inflammation in NASH needs further exploration.…”

Section: Protective Lipid Classesmentioning

confidence: 99%

Pathogenesis of Nonalcoholic Steatohepatitis: An Overview

2020

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Nonalcoholic fatty liver disease (NAFLD) is a heterogeneous group of liver diseases characterized by the accumulation of fat in the liver. The heterogeneity of NAFLD is reflected in a clinical and histologic spectrum where some patients develop isolated steatosis of the liver, termed nonalcoholic fatty liver, whereas others develop hepatocyte injury, ballooning, inflammation, and consequent fibrosis, termed nonalcoholic steatohepatitis (NASH). Systemic insulin resistance is a major driver of hepatic steatosis in NAFLD. Lipotoxicity of accumulated lipids along with activation of the innate immune system are major drivers of NASH. Lipid‐induced sublethal and lethal stress culminates in the activation of inflammatory processes, such as the release of proinflammatory extracellular vesicles and cell death. Innate and adaptive immune mechanisms involving macrophages, dendritic cells, and lymphocytes are central drivers of inflammation that recognize damage‐ and pathogen‐associated molecular patterns and contribute to the progression of the inflammatory cascade. While the activation of the innate immune system and the recruitment of proinflammatory monocytes into the liver in NASH are well known, the exact signals that lead to this remain less well defined. Further, the contribution of other immune cell types, such as neutrophils and B cells, is an area of intense research. Many host factors, such as the microbiome and gut–liver axis, modify individual susceptibility to NASH. In this review, we discuss lipotoxicity, inflammation, and the contribution of interorgan crosstalk in NASH pathogenesis.

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Mechanism of ER Stress and Inflammation for Hepatic Insulin Resistance in Obesity

Cited by 84 publications

References 75 publications

Outdoor Air Pollution and Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis

Outdoor Air Pollution and Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis

Plant Sterol Ester of α-Linolenic Acid Attenuates Nonalcoholic Fatty Liver Disease by Rescuing the Adaption to Endoplasmic Reticulum Stress and Enhancing Mitochondrial Biogenesis

Pathogenesis of Nonalcoholic Steatohepatitis: An Overview

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