C/EBP Homologous Protein (CHOP) Contributes to Suppression of Metabolic Genes during Endoplasmic Reticulum Stress in the Liver

Chikka, Madhusudana Rao; McCabe, Diane DeZwaan; Tyra, Heather M.; Rutkowski, D. Thomas

doi:10.1074/jbc.m112.432344

Cited by 98 publications

(82 citation statements)

References 59 publications

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“…Thus, the decreased NFκB activation paired with the increased CHOP suggests that the hepatic cell death pathway was activated. It should be noted that CHOP has also recently been shown to play a role in hepatic metabolic gene suppression, independent of its role in regulating apoptosis [42]. Thus, the increase in hepatic CHOP protein content in the HFD groups may explain the hepatic suppression of ACAC1 and SREBP-1.…”

Section: Discussionmentioning

confidence: 99%

A Low Dose of Dietary Quercetin Fails to Protect against the Development of an Obese Phenotype in Mice

et al. 2016

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The purpose of this study was to examine the effect of a 40% high-fat diet (HFD) supplemented with a dietary attainable level of quercetin (0.02%) on body composition, adipose tissue (AT) inflammation, Non-Alcoholic Fatty-Liver Disease (NAFLD), and metabolic outcomes. Diets were administered for 16 weeks to C57BL/6J mice (n = 10/group) beginning at 4 weeks of age. Body composition and fasting blood glucose, insulin, and total cholesterol concentrations were examined intermittently. AT and liver mRNA expression (RT-PCR) of inflammatory mediators (F4/80, CD206 (AT only), CD11c (AT only) TLR-2 (AT only), TLR-4 (AT only), MCP-1, TNF-α, IL-6 (AT only), and IL-10 (AT only)) were measured along with activation of NFκB-p65, and JNK (western blot). Hepatic lipid accumulation, gene expression (RT-PCR) of hepatic metabolic markers (ACAC1, SREBP-1, PPAR-γ), protein content of Endoplasmic Reticulum (ER) Stress markers (BiP, phosphorylated and total EIF2α, phosphorylated and total IRE1α, CHOP), and hepatic oxidative capacity were assessed (western blot). Quercetin administration had no effect at mitigating increases in visceral AT, AT inflammation, hepatic steatosis, ER Stress, decrements in hepatic oxidative capacity, or the development of insulin resistance and hypercholesterolemia. In conclusion, 0.02% quercetin supplementation is not an effective therapy for attenuating HFD-induced obesity development. It is likely that a higher dose of quercetin supplementation is needed to elicit favorable outcomes in obesity.

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Section: Discussionmentioning

confidence: 99%

A Low Dose of Dietary Quercetin Fails to Protect against the Development of an Obese Phenotype in Mice

et al. 2016

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“…Recent work also suggests that increased CHOP levels may have other metabolism-related roles in the cell. CHOP has recently been shown to be involved in binding to promoter regions involved in suppression of lipogenic genes in the liver (Chikka 2013). Overall, it appears that the levels of CHOP induced in response to stress ultimately determine the cellular response.…”

Section: Discussionmentioning

confidence: 99%

The effect of glucose concentration and sodium phenylbutyrate treatment on mitochondrial bioenergetics and ER stress in 3T3-L1 adipocytes

Tanis

Piroli

Day

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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While the 3T3-L1 adipocyte model is routinely used for the study of obesity and diabetes, the mitochondrial respiratory profile in normal versus high glucose has not been examined in detail. We matured adipocytes in normal (5 mM) or high (30 mM) glucose and insulin and examined the mitochondrial bioenergetics. We also assessed the requirement for the Unfolded Protein Response (UPR) and ER stress under these conditions. Basal respiration was ∼1.7-fold greater in adipocytes that had matured in 30 mM glucose; however, their ability to increase oxygen consumption in response to stress was impaired. Adipogenesis proceeded in both normal and high glucose with concomitant activation of the UPR, but only high glucose was associated with increased levels of ER stress and mitochondrial stress as observed by parallel increases in CHOP and protein succination. Treatment of adipocytes with sodium phenylbutyrate relieved mitochondrial stress through a reduction in mitochondrial respiration. Our data suggests that mitochondrial stress, protein succination and ER stress are uniquely linked in adipocytes matured in high glucose.

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“…2010; Chikka et al. 2013), impairment of triglyceride excretion (Zhang et al. 2011), or increased lipid delivery to the liver (Jo et al.…”

Section: Introductionmentioning

confidence: 99%

Role of endoplasmic reticulum stress in drug‐induced toxicity

Foufelle

Fromenty

2016

Pharmacology Res & Perspec

180

152

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Drug‐induced toxicity is a key issue for public health because some side effects can be severe and life‐threatening. These adverse effects can also be a major concern for the pharmaceutical companies since significant toxicity can lead to the interruption of clinical trials, or the withdrawal of the incriminated drugs from the market. Recent studies suggested that endoplasmic reticulum (ER) stress could be an important event involved in drug liability, in addition to other key mechanisms such as mitochondrial dysfunction and oxidative stress. Indeed, drug‐induced ER stress could lead to several deleterious effects within cells and tissues including accumulation of lipids, cell death, cytolysis, and inflammation. After recalling important information regarding drug‐induced adverse reactions and ER stress in diverse pathophysiological situations, this review summarizes the main data pertaining to drug‐induced ER stress and its potential involvement in different adverse effects. Drugs presented in this review are for instance acetaminophen (APAP), arsenic trioxide and other anticancer drugs, diclofenac, and different antiretroviral compounds. We also included data on tunicamycin (an antibiotic not used in human medicine because of its toxicity) and thapsigargin (a toxic compound of the Mediterranean plant Thapsia garganica) since both molecules are commonly used as prototypical toxins to induce ER stress in cellular and animal models.

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C/EBP Homologous Protein (CHOP) Contributes to Suppression of Metabolic Genes during Endoplasmic Reticulum Stress in the Liver

Cited by 98 publications

References 59 publications

A Low Dose of Dietary Quercetin Fails to Protect against the Development of an Obese Phenotype in Mice

A Low Dose of Dietary Quercetin Fails to Protect against the Development of an Obese Phenotype in Mice

The effect of glucose concentration and sodium phenylbutyrate treatment on mitochondrial bioenergetics and ER stress in 3T3-L1 adipocytes

Role of endoplasmic reticulum stress in drug‐induced toxicity

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