Hepatic Gene Networks in Morbidly Obese Patients With Nonalcoholic Fatty Liver Disease

Gawrieh, Samer; Baye, Tesfaye M.; Carless, Melanie A.; Wallace, James R.; Komorowski, Richard; Kleiner, David E.; Andris, Deborah A.; Makladi, Bassem; Cole, Regina; Charlton, Michael; Curran, Joanne E.; Dyer, Thomas D.; Charlesworth, Jac; Wilke, Russell A.; Blangero, John; Kissebah, Ahmed H.; Olivier, Michael

doi:10.1007/s11695-010-0171-6

Cited by 39 publications

(29 citation statements)

References 82 publications

(85 reference statements)

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“…A recent study analyzed hepatic gene networks in morbidly obese patients with NAFLD (BMI 49.6 ± 7.4 kg/m 2 , n = 24, 89% female) or without NAFLD (BMI 48.8 ± 5.9, kg/m 2 , n = 25, 96% female) (31). Three genes associated with the fibrosis pathway (COL1A1, IL10, and IGFBP3) were upregulated and one gene associated with the UPR (HSPA5, also known as GRP78) was downregulated in patients with NAFLD compared with patients without NAFLD.…”

Section: Activation Of the Upr In Human Obesity And Nafldmentioning

confidence: 99%

Endoplasmic Reticulum Stress in Nonalcoholic Fatty Liver Disease

2012

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The underlying causes of nonalcoholic fatty liver disease are unclear, although recent evidence has implicated the endoplasmic reticulum in both the development of steatosis and progression to nonalcoholic steatohepatitis. Disruption of endoplasmic reticulum homeostasis, often termed ER stress, has been observed in liver and adipose tissue of humans with nonalcoholic fatty liver disease and/or obesity. Importantly, the signaling pathway activated by disruption of endoplasmic reticulum homeostasis, the unfolded protein response, has been linked to lipid and membrane biosynthesis, insulin action, inflammation, and apoptosis. Therefore, understanding the mechanisms that disrupt endoplasmic reticulum homeostasis in nonalcoholic fatty liver disease and the role of the unfolded protein response in the broader context of chronic, metabolic diseases have become topics of intense investigation. The present review examines the endoplasmic reticulum and the unfolded protein response in the context of nonalcoholic fatty liver disease.

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Section: Activation Of the Upr In Human Obesity And Nafldmentioning

confidence: 99%

Endoplasmic Reticulum Stress in Nonalcoholic Fatty Liver Disease

2012

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“…Further, it may be advantageous to put focus on canonical pathways and networks instead of single genes when the aim is to obtain insight in the pathophysiology of complex diseases, such as preeclampsia. The high interconnectivity of focus genes with other correlated genes within a biological network may imply functional and biological importance of these genes 26, 27. To be able to assess this in a comprehensive manner, we increased the FDR cut off to 0.1 and consequently the number of genes included in the analysis.…”

Section: Commentmentioning

confidence: 99%

A transcriptional profile of the decidua in preeclampsia

Løset¹,

Mundal²,

Johnson³

et al. 2011

American Journal of Obstetrics and Gynecology

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OBJECTIVE-To obtain insight into possible mechanisms underlying preeclampsia using genome-wide transcriptional profiling in decidua basalis.STUDY DESIGN-Genome-wide transcriptional profiling was performed on decidua basalis tissue from preeclamptic (n = 37) and normal pregnancies (n = 58). Differentially expressed genes were identified and merged into canonical pathways and networks.RESULTS-Of the 26,504 expressed transcripts detected, 455 were differentially expressed (P <0.05, FDR P <0.1). Both novel (ARL5B, SLITRK4) and previously reported preeclampsiaassociated genes (PLA2G7, HMOX1) were identified. Pathway analysis revealed that 'tryptophan metabolism', 'endoplasmic reticulum stress', 'linoleic acid metabolism', 'notch signaling', 'fatty acid metabolism', 'arachidonic acid metabolism' and 'NRF2-mediated oxidative stress response' were overrepresented canonical pathways.CONCLUSION-In the present study single genes, canonical pathways and gene-gene networks that are likely to play an important role in the pathogenesis of preeclampsia, have been identified. Future functional studies are needed to accomplish a greater understanding of the mechanisms involved.

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“…Persistent activation of the UPR, on the other hand, is associated with the pathogenesis of a number of metabolic diseases [1, 2]. Chronic UPR activation has been observed in liver and/or adipose tissue of dietary and genetic murine models of obesity, and in human obesity and non-alcoholic fatty liver disease (NAFLD) [3–9]. Activation of the UPR typically occurs in response to the accumulation of unfolded proteins in the ER lumen, termed ER stress, however recent studies have demonstrated that ER membrane events independent of the ER lumen can trigger the UPR.…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic reticulum stress in obesity and obesity-related disorders: An expanded view

et al. 2016

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The Endoplasmic Reticulum (ER) is most notable for its central roles in calcium ion storage, lipid biosynthesis, and protein sorting and processing. By virtue of its extensive membrane contact sites that connect the ER to most other organelles and to the plasma membrane, the ER can also regulate diverse cellular processes including inflammatory and insulin signaling, nutrient metabolism, and cell proliferation and death via a signaling pathway called the unfolded protein response (UPR). Chronic UPR activation has been observed in liver and/or adipose tissue of dietary and genetic murine models of obesity, and in human obesity and non-alcoholic fatty liver disease (NAFLD). Activation of the UPR in obesity and obesity-related disorders likely has two origins. One linked to classic ER stress involving the ER lumen and one linked to alterations to the ER membrane environment. This review discusses both of these origins and also considers the role of post-translational protein modifications, such as acetylation and palmitoylation, and ER-mitochondrial interactions to obesity-mediated impairments in the ER and activation of the UPR.

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Hepatic Gene Networks in Morbidly Obese Patients With Nonalcoholic Fatty Liver Disease

Cited by 39 publications

References 82 publications

Endoplasmic Reticulum Stress in Nonalcoholic Fatty Liver Disease

Endoplasmic Reticulum Stress in Nonalcoholic Fatty Liver Disease

A transcriptional profile of the decidua in preeclampsia

Endoplasmic reticulum stress in obesity and obesity-related disorders: An expanded view

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