Signaling dynamics of palmitate-induced ER stress responses mediated by ATF4 in HepG2 cells

Cho, Hyun-Ju; Wu, Ming; Zhang, Linxia; Thompson, Ryan; Nath, Aritro; Chan, Christina

doi:10.1186/1752-0509-7-9

Cited by 40 publications

(43 citation statements)

References 42 publications

(58 reference statements)

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“…We also found that palimtic acid induces ATF4 and FGF21 gene expression in FaO cells, while oleic acid increased gene expression of FGF21 but not ATF4. Based on previous reports showing the positive effect of palmitic acid on ATF4 expression and that of oleic acid on PPARα transcriptional activity [24], [25], we speculate that FFAs released from adipose tissue by acute exercise-induced lipolysis both induce gene expression of ATF4 and enhance the transcriptional activity of PPARα in the liver, leading to the synergistically increased hepatic FGF21 expression.…”

Section: Discussionsupporting

confidence: 58%

Acute Exercise Induces FGF21 Expression in Mice and in Healthy Humans

et al. 2013

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Fibroblast growth factor 21 (FGF21) plays an important role in the regulation of energy homeostasis during starvation and has an excellent therapeutic potential for the treatment of type 2 diabetes in rodents and monkeys. Acute exercise affects glucose and lipid metabolism by increasing glucose uptake and lipolysis. However, it is not known whether acute exercise affects FGF21 expression. Here, we showed that serum FGF21 level is increased in mice after a single bout of acute exercise, and that this is accompanied by increased serum levels of free fatty acid, glycerol and ketone body. FGF21 gene expression was induced in the liver but not in skeletal muscle and white adipose tissue of mice after acute exercise, and further, the gene expression levels of hepatic peroxisome proliferator-activated receptor α (PPARα) and activating transcription factor 4 (ATF4) were also increased. In addition, we observed increased FGF21 level in serum of healthy male volunteers performing a treadmill run at 50 or 80% VO2max. These results suggest that FGF21 may also be associated with exercise-induced lipolysis in addition to increased catecholamines and reduced insulin.

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Section: Discussionsupporting

confidence: 58%

Acute Exercise Induces FGF21 Expression in Mice and in Healthy Humans

et al. 2013

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“…In addition, NLRC4 and ASC levels are upregulated in the brains of AD patients (Liu and Chan, 2014), suggesting a possible role of the NLRC4 inflammasome in AD pathogenesis. In support, palmitate induces IL-1β release from HepG2 (hepatocellular carcinoma cells), and knockdown of NLRC4 inhibits the palmitate induced inflammation and cytokine release (Cho et al, 2013; Luo et al, 2012). Fatty acids can also cause the release of IL-1β from microglia, but the specific inflammasome that regulates this process has not been identified (Wang et al, 2012).…”

Section: Fatty Acids Involvement In Inflammasome Activation and Pamentioning

confidence: 95%

The role of inflammasome in Alzheimer's disease

Liu

Chan

2014

Ageing Research Reviews

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164

105

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Alzheimer’s disease (AD) is a chronic, progressive and irreversible neurodegenerative disease with clinical characteristics of memory loss, dementia and cognitive impairment. Although the pathophysiologic mechanism is not fully understood, inflammation has been shown to play a critical role in the pathogenesis of AD. Inflammation in the central nervous system (CNS) is characterized by the activation of glial cells and release of proinflammatory cytokines and chemokines. Accumulating evidence demonstrates that inflammasomes, which cleaves precursors of interleukin-1β (IL-1β) and IL-18 to generate their active forms, play an important role in the inflammatory response in the CNS and in AD pathogenesis. Therefore, modulating inflammasome complex assembly and activation could be a potential strategy for suppressing inflammation in the CNS. This review aims to provide insight into the role of inflammasomes in the CNS, with respect to the pathogenesis of AD, and may provide possible clues for devising novel therapeutic strategies.

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“…Elevated blood levels of NEFA are considered important inducers of ER stress in the liver, based on the observation that metabolic conditions associated with elevated plasma NEFA levels, such as obesity or diabetes, lead to ER stress in the liver (Kharroubi et al., ; Cnop et al., ; Kawasaki et al., ). Obviously, this effect is dependent on the type of fatty acids, because saturated fatty acids produce ER stress in several cell types, including hepatocytes, whereas unsaturated fatty acids do not (Borradaile et al., ; Wei et al., ; Cho et al., ). In line with this, infusion of lard oil (enriched in saturated fatty acids) resulted in a stronger induction of ER stress in the liver than soybean oil (enriched in unsaturated fatty acids; Nivala et al., ).…”

Section: Role Of Er Stress For Fatty Liver and Ketosis Developmentmentioning

confidence: 99%

Molecular insights into the mechanisms of liver‐associated diseases in early‐lactating dairy cows: hypothetical role of endoplasmic reticulum stress

Ringseis

Geßner

Eder

2014

Animal Physiology Nutrition

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SummaryThe transition period represents the most critical period in the productive life of high-yielding dairy cows due to both metabolic and inflammatory stimuli, which challenge the liver and predispose dairy cows to develop liverassociated diseases such as fatty liver and ketosis. Despite the fact that all high-yielding dairy cows are affected by marked metabolic stress due to a severe negative energy balance (NEB) during early lactation, not all cows develop liver-associated diseases. Although the reason for this is largely unknown, this indicates that the capacity of the liver to cope with metabolic and inflammatory challenges varies between individual high-yielding dairy cows. Convincing evidence exists that endoplasmic reticulum (ER) stress plays a key role in the development of fatty liver, and it has been recently shown that ER stress occurs in the liver of high-yielding dairy cows. This indicates that ER stress may be involved in the development of liver-associated diseases in dairy cows. The present review shows that the liver of dairy cows during early lactation is exposed to several metabolic and inflammatory challenges, such as non-esterified fatty acids, tumour necrosis factor a, interleukin-1b, reactive oxygen species and lipopolysaccharides, which are known inducers of ER stress. Thus, ER stress may represent a molecular basis for fatty liver development and account for the frequent occurrence of fatty liver and ketosis in high-yielding dairy cows. Interindividual differences between dairy cows in the activation of hepatic stress response pathways, such as nuclear factor E2-related factor 2, which is activated during ER stress and reduces the sensitivity of tissues to oxidative and inflammatory damage, might provide an explanation at the molecular level for differences in the capacity to cope with pathological inflammatory challenges during early lactation and the susceptibility to develop liver-associated diseases between early-lactating dairy cows with similar NEB and milk yield.

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Signaling dynamics of palmitate-induced ER stress responses mediated by ATF4 in HepG2 cells

Cited by 40 publications

References 42 publications

Acute Exercise Induces FGF21 Expression in Mice and in Healthy Humans

Acute Exercise Induces FGF21 Expression in Mice and in Healthy Humans

The role of inflammasome in Alzheimer's disease

Molecular insights into the mechanisms of liver‐associated diseases in early‐lactating dairy cows: hypothetical role of endoplasmic reticulum stress

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