Lipid overload impairs hepatic VLDL secretion via oxidative stress-mediated PKCδ-HNF4α-MTP pathway in large yellow croaker (Larimichthys crocea)

Fang, Wei; Chen, Qiuchi; Chen, Qiang; Li, Xueshan; Xu, Ning; Mai, Kangsen; Ai, Qinghui

doi:10.1016/j.freeradbiomed.2021.06.001

Cited by 26 publications

(14 citation statements)

References 58 publications

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“…Similar to our data, a previous study reported that MTTP-deficient patients showed impaired exports of VLDL from the liver, thereby resulting in the development of steatosis with the accumulation of triglycerides in the liver [47]. Moreover, a recent study indicated that excessive lipid overload-induced oxidative stress resulted in the suppression of MTTP through protein kinase C delta and hepatocyte nuclear factor 4 alpha, which impaired VLDL secretion in the liver of fish [48]. Similar to these data, our results showed that the suppression of oxidative stress using the antioxidant NAC caused a lower level of lipid accumulation, compared to that in TEB-treated cells.…”

Section: Discussionsupporting

confidence: 90%

Tebuconazole Fungicide Induces Lipid Accumulation and Oxidative Stress in HepG2 Cells

Kwon

Kim

Jeong³

et al. 2021

Foods

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Tebuconazole (TEB), a triazole fungicide, is frequently applied to agriculture for the increase of food production. Although TEB causes liver toxicity, its effects on cellular lipid accumulation are rarely investigated. Therefore, this study aimed to study the effects of TEB on lipid metabolism and accumulation in HepG2 cells. HepG2 cells were exposed to 0–320 µM TEB for 1–24 h. TEB (20–80 µM, 24 h)-treated cells showed lipid accumulation. Further, TEB (20–80 µM, 1–12 h) increased the nuclear translocation of peroxisome proliferator-activated receptors and the expression of lipid uptake and oxidation-related markers such as cluster of differentiation 36, fatty acid transport protein (FATP) 2, FATP5, and carnitine palmitoyltransferase 1. Oxidative stress levels in TEB-treated cells (20–80 µM, 24 h) were higher, compared to those in the control. TEB (20–80 µM, 24 h) also induced the loss of mitochondrial membrane potential and lower levels of microsomal triglyceride transfer protein in the cells. Thus, TEB can induce lipid accumulation by altering the expression of lipid-metabolizing molecules and can therefore impair lipid metabolism. Our data suggest that human exposure to TEB may be a risk factor for non-alcoholic fatty liver disease.

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Section: Discussionsupporting

confidence: 90%

Tebuconazole Fungicide Induces Lipid Accumulation and Oxidative Stress in HepG2 Cells

Kwon

Kim

Jeong³

et al. 2021

Foods

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“…The TG content was analyzed according to a previous study (20). After TM treatment for 12 h, cells were incubated with BODIPY 493/503 (Sigma) for 10 min, washed with phosphate buffer solution (PBS, Solarbio) three times, and then immediately observed lipid droplets in the cells with a fluorescent microscope (Nikon, Japan), according to the methods in a previous study (21).…”

Section: Tg Content and Lipid Droplet Stainingmentioning

confidence: 99%

Endoplasmic Reticulum Stress Disturbs Lipid Homeostasis and Augments Inflammation in the Intestine and Isolated Intestinal Cells of Large Yellow Croaker (Larimichthys crocea)

Fang

Chen

et al. 2021

Front. Immunol.

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The small intestine is crucial for lipid homeostasis and immune regulation of the whole body. Endoplasmic reticulum (ER) stress may affect lipid metabolism and inflammation in the intestine, but the potential mechanism is not completely understood. In the present study, intraperitoneal injection of tunicamycin (TM) induced ER stress in the intestine of large yellow croaker (Larimichthys crocea). ER stress induced excessive accumulation of triglyceride (TG) in the intestine by promoting lipid synthesis. However, it also enhanced lipid secretion and fatty acid β-oxidation. In addition, ER stress augmented inflammation in the intestine by promoting p65 into the nucleus and increasing proinflammatory genes expression. In the isolated intestinal cells, the obtained results showed that TM treatment significantly upregulated the mRNA expression of lipid synthesis and inflammatory response genes, which were consistent with those in vivo. Moreover, overexpression of unfolded protein response (UPR) sensors significantly upregulated promoter activities of lipid synthesis and proinflammatory genes. In conclusion, the results suggested that ER stress disturbed lipid metabolism and augmented inflammation in the intestine and isolated intestinal cells of large yellow croaker, which may contribute to finding novel therapies to tackle lipid dysregulation and inflammation in the intestine of fish and human beings.

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“…The change of intracellular reactive oxygen species (ROS) was determined according to the accompanying instructions of the reactive oxygen species detection kit (Beyotime Institute of Technology, China) and Fang et al. ( 25 ). In brief, cells were cultured in 96-well plates with DMEM/F12, stimulated with fatty acids for 12 h, then loaded with cell-permeable 2’, 7’ dichlorofluorescein diacetate (DCFH-DA).…”

Section: Methodsmentioning

confidence: 99%

Octanoate Alleviates Dietary Soybean Oil-Induced Intestinal Physical Barrier Damage, Oxidative Stress, Inflammatory Response and Microbial Dysbiosis in Large Yellow Croaker (Larimichthys Crocea)

et al. 2022

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Octanoate is a type of classical medium-chain fatty acids, which is widely used to treat neurological and metabolic syndrome. However, the specific role of octanoate in repairing intestinal health impairment is currently unknown. Therefore, we investigated whether dietary octanoate repaired the intestinal damage induced by surplus soybean oil in Larimichthys crocea. In this study, dietary octanoate alleviated abnormal morphology of the intestine and enhanced expression of ZO-1 and ZO-2 to improve intestinal physical barrier. Further, dietary octanoate increased antioxidant enzymic activities and decreased the level of ROS to alleviate the intestinal oxidative stress. Dietary octanoate also attenuated the expression of proinflammatory cytokines and the polarity of macrophage to reduce the intestinal inflammatory response. Moreover, the result of intestinal microbial 16S rRNA sequence showed that dietary octanoate repaired the intestinal mucosal microbial dysbiosis, and increased the relative abundance of Lactobacillus. Dietary octanoate supplementation also increased the level of acetic acid in intestinal content and serum through increasing the abundance of acetate-producing strains. Overall, in Larimichthys crocea, dietary octanoate might alleviated oxidative stress, inflammatory response and microbial dysbiosis to repair the intestinal damage induced by surplus soybean oil. This work provides vital insights into the underlying mechanisms and treatment strategies for intestinal damage in vertebrates.

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Lipid overload impairs hepatic VLDL secretion via oxidative stress-mediated PKCδ-HNF4α-MTP pathway in large yellow croaker (Larimichthys crocea)

Cited by 26 publications

References 58 publications

Tebuconazole Fungicide Induces Lipid Accumulation and Oxidative Stress in HepG2 Cells

Tebuconazole Fungicide Induces Lipid Accumulation and Oxidative Stress in HepG2 Cells

Endoplasmic Reticulum Stress Disturbs Lipid Homeostasis and Augments Inflammation in the Intestine and Isolated Intestinal Cells of Large Yellow Croaker (Larimichthys crocea)

Octanoate Alleviates Dietary Soybean Oil-Induced Intestinal Physical Barrier Damage, Oxidative Stress, Inflammatory Response and Microbial Dysbiosis in Large Yellow Croaker (Larimichthys Crocea)

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