Free Fatty Acids Increase Intracellular Lipid Accumulation and Oxidative Stress by Modulating PPARα and SREBP‐1c in L‐02 Cells

Qin, Shumin; Yin, Jinjin; Huang, Keer

doi:10.1007/s11745-016-4160-y

Cited by 39 publications

(35 citation statements)

References 31 publications

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“…The authors reported that high concentration of free fatty acid induced excessive lipid accumulation and oxidative stress by down-regulating the ppara expression, similar to our observations [49]. PPARα is nuclear hormone receptors, and regulates the expression of many genes involved in fatty acid oxidation, ketogenesis, gluconeogenesis, cholesterol catabolism, among others.…”

Section: Discussionsupporting

confidence: 90%

“…Recently, a study developed with a mammalian model of hepatocellular steatosis established the effects of free fatty acid and the mechanism associated to oxidative stress [49]. The authors reported that high concentration of free fatty acid induced excessive lipid accumulation and oxidative stress by down-regulating the ppara expression, similar to our observations [49].…”

Section: Discussionsupporting

confidence: 87%

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Transcriptomic analysis of the hepatic response to stress in the red cusk-eel (Genypterus chilensis): Insights into lipid metabolism, oxidative stress and liver steatosis

et al. 2017

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Teleosts exhibit a broad divergence in their adaptive response to stress, depending on the magnitude, duration, and frequency of stressors and the species receiving the stimulus. We have previously reported that the red cusk-eel (Genypterus chilensis), an important marine farmed fish, shows a physiological response to stress that results in increased skeletal muscle atrophy mediated by over-expression of components of the ubiquitin proteasome and autophagy-lysosomal systems. To better understand the systemic effects of stress on the red cusk-eel metabolism, the present study assessed the transcriptomic hepatic response to repetitive handling-stress. Using high-throughput RNA-seq, 259 up-regulated transcripts were found, mostly associated with angiogenesis, gluconeogenesis, and triacylglyceride catabolism. Conversely, 293 transcripts were down-regulated, associated to cholesterol biosynthesis, PPARα signaling, fatty acid biosynthesis, and glycolysis. This gene signature was concordant with hepatic metabolite levels and hepatic oxidative damage. Moreover, the increased plasmatic levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase) and AP (alkaline phosphatase), as well as liver histology suggest stress-induced liver steatosis. This study offers an integrative molecular and biochemical analysis of the hepatic response to handling-stress, and reveals unknown aspects of lipid metabolism in a non-model teleost.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 87%

Transcriptomic analysis of the hepatic response to stress in the red cusk-eel (Genypterus chilensis): Insights into lipid metabolism, oxidative stress and liver steatosis

et al. 2017

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“…On the other hand, SREBP-1c and patatin-like phospholipase domain-containing protein 3 (PNPLA-3) pathways may affect the progression of NASH [39,40]. The pathway may be associated with inflammation [41] and oxidative stress [42]. PNPLA-3 has been reported to be related to the increase in the level of total glycerol and risk of hepatic injuries [43].…”

Section: Introductionmentioning

confidence: 99%

The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) by Affecting SREBP-1c/PNPLA-3 Pathway via PPAR-α

Ren

Zhu

et al. 2017

Nutrients

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Nonalcoholic steatohepatitis (NASH) is liver inflammation and a major threat to public health. Several pharmaceutical agents have been used for NASH therapy but their high-rate side effects limit the use. Blueberry juice and probiotics (BP) have anti-inflammation and antibacterial properties, and may be potential candidates for NASH therapy. To understand the molecular mechanism, Sprague Dawley rats were used to create NASH models and received different treatments. Liver tissues were examined using HE (hematoxylin and eosin) and ORO (Oil Red O) stain, and serum biochemical indices were measured. The levels of peroxisome proliferators-activated receptor (PPAR)-α, sterol regulatory element binding protein-1c (SREBP-1c), Patatin-like phospholipase domain-containing protein 3 (PNPLA-3), inflammatory cytokines and apoptosis biomarkers in liver tissues were measured by qRT-PCR and Western blot. HE and ORO analysis indicated that the hepatocytes were seriously damaged with more and larger lipid droplets in NASH models while BP reduced the number and size of lipid droplets (p < 0.05). Meanwhile, BP increased the levels of SOD (superoxide dismutase), GSH (reduced glutathione) and HDL-C (high-density lipoprotein cholesterol), and reduced the levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), TG (triglycerides), LDL-C (low-density lipoprotein cholesterol) and MDA (malondialdehyde) in NASH models (p < 0.05). BP increased the level of PPAR-α (Peroxisome proliferator-activated receptor α), and reduced the levels of SREBP-1c (sterol regulatory element binding protein-1c) and PNPLA-3 (Patatin-like phospholipase domain-containing protein 3) (p < 0.05). BP reduced hepatic inflammation and apoptosis by affecting IL-6 (interleukin 6), TNF-α (Tumor necrosis factor α), caspase-3 and Bcl-2 in NASH models. Furthermore, PPAR-α inhibitor increased the level of SREBP-1c and PNPLA-3. Therefore, BP prevents NASH progression by affecting SREBP-1c/PNPLA-3 pathway via PPAR-α.

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“…The L-02 cells were cultured in RPMI 1640 medium (Gibco, California, USA) supplemented with 10% fetal bovine serum (FBS) (Gibco, California, USA), 100 U/mL penicillin and 100 U/mL streptomycin (Gibco, California, USA) for 24 hours. All the cell lines were maintained at 37°C in a humidified incubator with an atmosphere of 5% CO 2 (Qin et al, 2016).…”

Section: Cell Culturementioning

confidence: 99%

“…Sodium palmitate and oleate (Sigma, New York, USA) were added to the H2O2 and NaOH solutions, respectively, and then, they were added to a 10% solution of fatty-acid-free bovine serum albumin (BSA) (Sangon Biotech, Shanghai, China), which was dissolved overnight at 55°C with gentle shaking; then, the mixture was cooled to room temperature, filtered and stored at 4°C in a refrigerator (Qin et al, 2016).…”

Section: Preparation Of Ffa Culture Mediummentioning

confidence: 99%

Peer Review #1 of "Huperzine A attenuates nonalcoholic fatty liver disease by regulating hepatocyte senescence and apoptosis: an in vitro study (v0.2)"

Zhou¹

2018

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This study was undertaken to detect if free fatty acids (FFA) induce hepatocyte senescence in L-02 cells and if huperzine A has an anti-aging effect in fatty liver cells. Methods: L-02 cells were treated with a FFA mixture (oleate/palmitate, at 3:0, 2:1, 1:1, 1:2 and 0:3 ratios) at different concentrations. Cell viability and fat accumulation rate were assessed by a Cell Counting Kit 8 (CCK8) kit and Nile Red staining, respectively. The Objective: This study was undertaken to detect if free fatty acids (FFA) induce hepatocyte senescence in L-02 cells and if huperzine A has an anti-aging effect in fatty liver cells. Methods: L-02 cells were treated with a FFA mixture (oleate/palmitate, at 3:0, 2:1, 1:1, 1:2 and 0:3 ratios) at different concentrations. Cell viability and fat accumulation rate were assessed by a Cell Counting Kit 8 (CCK8) and Nile Red staining, respectively. The mixture with the highest cell viability and fat accumulation rate was selected to continue with the following experiment. The L-02 cells were divided into five groups, including the control group, FFA group, FFA+0.1 μmol/L huperzine A (LH) group, FFA+1.0 μmol/L huperzine A (MH) group and FFA+10 μmol/L huperzine A (HH) group, and were cultured for 24 h. The expression of senescence-associated β-galactosidase (SA-β-gal) was detected by a SA-β-gal staining kit. The expression levels of aging genes were measured by qRT-PCR. The expression levels of apoptosis proteins were detected by a Western blot. ELISA kits were used to detect inflammatory factors and oxidative stress products. The expression of NF-κB and IκBα were detected by immunofluorescence. Results: The FFA mixture (oleate/palmitate, at a 2:1 ratio) of 0.5 mmol/L had the highest cell viability and fat accumulation rate, which was preferable for establishing an in vitro fatty liver model. The expression of inflammatory factors (TNFα, IL-6, and IL-10) and oxidants (MDA, HNE and ROS) also increased in the L-02 fatty liver cells. The expression levels of aging markers and aging genes, such as SA-β-gal, p16, p21, p53 and pRb, increased more in the L-02 fatty liver cells than in the L-02 cells. The total levels of the apoptosisassociated proteins Bcl2, Bax, Bax/Bcl-2, CyCt, and cleaved caspase 9 were also upregulated in the L-02 fatty liver cells. All of the above genes and proteins were downregulated in the huperzine A and FFA co-treatment group. In the L-02 fatty liver cells, the expression of IκBα decreased, while the expression of NF-κB increased. After the huperzine A and FFA co-treatment, the expression of IκBα increased, while the expression of NF-κB decreased. Conclusion: Fatty liver cells showed an obvious senescence and apoptosis phenomenon. Huperzine A suppressed hepatocyte senescence, and it might exert its anti-aging effect via the NF-κB pathway.

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Free Fatty Acids Increase Intracellular Lipid Accumulation and Oxidative Stress by Modulating PPARα and SREBP‐1c in L‐02 Cells

Cited by 39 publications

References 31 publications

Transcriptomic analysis of the hepatic response to stress in the red cusk-eel (Genypterus chilensis): Insights into lipid metabolism, oxidative stress and liver steatosis

Transcriptomic analysis of the hepatic response to stress in the red cusk-eel (Genypterus chilensis): Insights into lipid metabolism, oxidative stress and liver steatosis

The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) by Affecting SREBP-1c/PNPLA-3 Pathway via PPAR-α

Peer Review #1 of "Huperzine A attenuates nonalcoholic fatty liver disease by regulating hepatocyte senescence and apoptosis: an in vitro study (v0.2)"

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