The role of X-box binding protein 1 in the hepatic response to refeeding in mice

Olivares, Shantel; Henkel, Anne S.

doi:10.1194/jlr.m086413

Cited by 8 publications

(10 citation statements)

References 48 publications

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“…The same publication showed that Xbp1s LKO mice had decreased plasma levels of TGs, due to an impaired secretion by the liver, in both fasting and refeeding states. This strengthened the idea that the function of XBP1s in hepatic lipid metabolism is not restricted to lipogenesis 74 . A similar observation was made during the characterization of a conditional postnatal Xbp1 KO in mice liver, in which decreased levels of plasma TGs, cholesterol and free FAs were observed in KO animals compared to controls 70 .…”

Section: Regulation Of Lipid Metabolism By the Uprsupporting

confidence: 77%

“…This strengthened the idea that the function of XBP1s in hepatic lipid metabolism is not restricted to lipogenesis. 74 A similar observation was made during the characterization of a conditional postnatal Xbp1 KO in mice liver, in which decreased levels of plasma TGs, cholesterol and free FAs were observed in KO animals compared to controls. 70 A possible explanation for these results came from a later study which showed that XBP1 overexpression was able to revert deficient secretion of TGs in hepatocytes from liver-specific Ern1a KO mice by increasing protein disulphide isomerase (PDI) expression.…”

Section: Regulation Of Lipid Metabolism By Ire1αsupporting

confidence: 66%

“…In liver‐specific Xbp1 KO ( Xbp1 LKO) mice, hepatic XBP1s expression was required for the translation, but not transcription, of de novo lipogenesis genes such as Srebp1c , Fasn and Acac 74 . This effect was linked to a phospho‐eIF2α‐induced arrest in global translation, leading to the conclusion that, while XBP1s might not be necessary for the transcriptional induction of lipogenic genes, its activity is necessary to manage fasting and refeeding states in the liver 74 . The same publication showed that Xbp1s LKO mice had decreased plasma levels of TGs, due to an impaired secretion by the liver, in both fasting and refeeding states.…”

Section: Regulation Of Lipid Metabolism By the Uprmentioning

confidence: 99%

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Regulation of lipid metabolism by the unfolded protein response

Moncan

Mnich

Blomme

et al. 2021

J Cellular Molecular Medi

115

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The endoplasmic reticulum (ER) is the site of protein folding and secretion, Ca 2+ storage and lipid synthesis in eukaryotic cells. Disruption to protein folding or Ca 2+ homeostasis in the ER leads to the accumulation of unfolded proteins, a condition known as ER stress. This leads to activation of the unfolded protein response (UPR) pathway in order to restore protein homeostasis. Three ER membrane proteins, namely inositol‐requiring enzyme 1 (IRE1), protein kinase RNA‐like ER kinase (PERK) and activating transcription factor 6 (ATF6), sense the accumulation of unfolded/misfolded proteins and are activated, initiating an integrated transcriptional programme. Recent literature demonstrates that activation of these sensors can alter lipid enzymes, thus implicating the UPR in the regulation of lipid metabolism. Given the presence of ER stress and UPR activation in several diseases including cancer and neurodegenerative diseases, as well as the growing recognition of altered lipid metabolism in disease, it is timely to consider the role of the UPR in the regulation of lipid metabolism. This review provides an overview of the current knowledge on the impact of the three arms of the UPR on the synthesis, function and regulation of fatty acids, triglycerides, phospholipids and cholesterol.

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Section: Regulation Of Lipid Metabolism By the Uprsupporting

confidence: 77%

Section: Regulation Of Lipid Metabolism By Ire1αsupporting

confidence: 66%

Section: Regulation Of Lipid Metabolism By the Uprmentioning

confidence: 99%

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Regulation of lipid metabolism by the unfolded protein response

Moncan

Mnich

Blomme

et al. 2021

J Cellular Molecular Medi

115

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“…65 Mice lacking hepatic XBP1 had markedly decreased mRNA levels of SREBP1, FAS, and ACC1. 66,67 It has been reported that the RNAi-mediated knockdown of ATF6 in hepatocytes could block fatty acid-induced SREBP-1c expression. 68 In this study, the expression of proteins related to ERS and lipogenesis were measured, and our findings agreed with those of previous studies.…”

Section: ■ Discussionmentioning

confidence: 99%

Preventive Effect of Apple Polyphenol Extract on High-Fat Diet-Induced Hepatic Steatosis in Mice through Alleviating Endoplasmic Reticulum Stress

Yan

Chen

Wang

et al. 2022

J. Agric. Food Chem.

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In this work, the protective effect of apple polyphenol extract (APE) on hepatic steatosis was investigated. Thirty-two C57BL/6J mice were assigned randomly to control group, hepatic steatosis group, lovastatin group, and APE group. After 8 weeks of intervention, APE supplementation markedly decreased the body weight gain, liver weight, liver index, epididymal adipose weight, epididymal adipose index, serum, and hepatic lipid levels. Hematoxylin and eosin staining revealed that APE supplementation alleviated histopathological changes of hepatic steatosis. Western blot revealed that APE downregulated the protein levels of GRP78, IRE1α, p-IRE1α, XBP1, PERK, p-PERK, p-eIF2α, ATF6, PPAR-γ, SREBP-1c, FAS, and ACC1. In conclusion, this study found that APE inhibited IRE1α-XBP1, PERK-eIF2α, and ATF6 signaling pathways to alleviate endoplasmic reticulum stress, thereby improving HFD-induced hepatic steatosis.

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“…The contribution of the other two arms of the UPR to the regulation of lipid metabolism is also evident. Inositol-requiring enzyme 1a (IRE1a) regulates lipid metabolism via X-box binding protein 1 (XBP1) and regulated IRE1dependent decay (RIDD), to control the transport of triglycerides and proliferator-activated receptor a (PPARa)-mediated lipolysis, and to promote lipid hydrolysis and prevent lipid storage, respectively [50][51][52]. Examples of the regulation of lipid metabolism through eukaryotic Initiation Factor 2 (eIF2a), ATF4 and C/EBP homologous protein (CHOP), which constitute downstream targets of protein kinase RNA-like ER Kinase (PERK) signaling, include lipogenesis, and FA elongation and FA desaturation [53,54].…”

Section: Triangular Interplay Between Cellular Stress Lipid Metabolis...mentioning

confidence: 99%

Dysregulated lipid metabolism in colorectal cancer

Coleman¹,

Ecker²,

Haller

2021

Current Opinion in Gastroenterology

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Purpose of reviewLipid metabolism presents a targetable metabolic vulnerability in colorectal cancer (CRC). Lipid signatures and cancer-cell lipid requirements may serve as noninvasive diagnostic and prognostic biomarkers and as a therapeutic target, respectively. Recent findingsA growing body of new studies highlight the complexity of lipid metabolism in CRC. Cancer cells are able to utilize an alternative fatty acid desaturation pathway, underlining the metabolic plasticity of tumors. CRC tissue shows a robust triglyceride-species signature with prognostic value in CRC patients. Lipidomic analyses in germfree and colonized mice identify a unique lipid signature and suggest that bacteria inhibit metabolism of polyunsaturated fatty acids by blocking desaturase and elongase activities. Cellular stress responses, particularly the well characterized unfolded protein response, are involved in regulating lipid synthesis and homeostasis, and contribute to adaptation of the lipid environment. Together, lipid metabolism, the intestinal microbiota and cellular stress responses unarguably play crucial roles in CRC. SummaryA number of recent advances in our understanding of dysregulated lipid metabolism in CRC underline the importance of this research field. An improved knowledge of the complex interplay between lipid metabolism, cellular stress and the intestinal microbiota in the context of CRC may lead to novel therapeutic strategies.

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The role of X-box binding protein 1 in the hepatic response to refeeding in mice

Cited by 8 publications

References 48 publications

Regulation of lipid metabolism by the unfolded protein response

Regulation of lipid metabolism by the unfolded protein response

Preventive Effect of Apple Polyphenol Extract on High-Fat Diet-Induced Hepatic Steatosis in Mice through Alleviating Endoplasmic Reticulum Stress

Dysregulated lipid metabolism in colorectal cancer

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