SREBP-1 and LXRα pathways mediated Cu-induced hepatic lipid metabolism in zebrafish Danio rerio

Pan, Ya–Xiong; Zhuo, Mei‐Qing; Li, Dandan; Xu, Yi-Huan; Wu, Kun-Lung; Luo, Zhi

doi:10.1016/j.chemosphere.2018.10.058

Cited by 43 publications

(29 citation statements)

References 43 publications

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“…FAS catalyses malonyl‐CoA into palmitate. SCD1 catalyses the synthesis of monounsaturated fatty acids, which are then incorporated into TGs and phospholipids; DGATs are also important to synthesize fatty acids into TGs . The elevated levels of these genes indicated that T0901317 treatment might increase the de novo lipogenesis in RAW264.7 cells and HepG2 cells, which were consistent with previous studies .…”

Section: Discussionsupporting

confidence: 91%

“…LXR antagonists GSK2033 and SR9243 efficiently decreased the expression of LXRα and its target genes, such as ABCA1, and abolished the effects of LXR agonist T0901317 (Figure ). However, GSK2033 and SR9243 had no effect on cellular levels of lipids (Figure ), consistent with previous studies . For example, although GSK2033 significantly reduced the protein levels of LXRα, it showed no significant effect on lipid accumulation in apolipoprotein E‐deficient mice and foam cell formation of RAW264.7 cells compared to the model group .…”

Section: Discussionsupporting

confidence: 89%

“…For example, although GSK2033 significantly reduced the protein levels of LXRα, it showed no significant effect on lipid accumulation in apolipoprotein E‐deficient mice and foam cell formation of RAW264.7 cells compared to the model group . Furthermore, SR9243 showed no effect on the TG accumulation in zebrafish hepatocytes . These promiscuous activities of the LXR antagonists may be due to their unexpected effects on lipogenic genes.…”

Section: Discussionmentioning

confidence: 92%

“…However, GSK2033 and SR9243 had no effect on cellular levels of lipids ( Figure 5), consistent with previous studies. [39][40][41] For example, although GSK2033 significantly reduced the protein levels of LXRα, it showed no significant effect on lipid accumulation in apolipoprotein E-deficient mice and foam cell formation of RAW264.7 cells compared to the model group. 39 Furthermore, SR9243 showed no effect on the TG accumulation in zebrafish hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

“…39 Furthermore, SR9243 showed no effect on the TG accumulation in zebrafish hepatocytes. 40 These promiscuous activities of the LXR antagonists may be due to their unexpected effects on lipogenic genes. For instance, GSK2033 could significantly improve rather than suppress the expression of the lipogenic genes such as FAS and SREBP-1c and therefore had no effect on hepatic steatosis in a mouse model of non-alcoholic fatty liver disease.…”

Section: Discussionmentioning

confidence: 99%

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The marine‐derived furanone reduces intracellular lipid accumulation in vitro by targeting LXRα and PPARα

Pang

et al. 2020

J Cellular Molecular Medi

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Recent studies have demonstrated that commercially available lipid‐lowering drugs cause various side effects; therefore, searching for anti‐hyperlipidaemic compounds with lower toxicity is a research hotspot. This study was designed to investigate whether the marine‐derived compound, 5‐hydroxy‐3‐methoxy‐5‐methyl‐4‐butylfuran‐2(5H)‐one, has an anti‐hyperlipidaemic activity, and the potential underlying mechanism in vitro. Results showed that the furanone had weaker cytotoxicity compared to positive control drugs. In RAW 264.7 cells, the furanone significantly lowered ox‐LDL‐induced lipid accumulation (~50%), and its triglyceride (TG)‐lowering effect was greater than that of liver X receptor (LXR) agonist T0901317. In addition, it significantly elevated the protein levels of peroxisome proliferator‐activated receptors (PPARα) and ATP‐binding cassette (ABC) transporters, which could be partially inhibited by LXR antagonists, GSK2033 and SR9243. In HepG2 cells, it significantly decreased oleic acid‐induced lipid accumulation, enhanced the protein levels of low‐density lipoprotein receptor (LDLR), ABCG5, ABCG8 and PPARα, and reduced the expression of sterol regulatory element‐binding protein 2 (~32%). PPARα antagonists, GW6471 and MK886, could significantly inhibit the furanone‐induced lipid‐lowering effect. Furthermore, the furanone showed a significantly lower activity on the activation of the expression of lipogenic genes compared to T0901317. Taken together, the furanone exhibited a weak cytotoxicity but had powerful TC‐ and TG‐lowering effects most likely through targeting LXRα and PPARα, respectively. These findings indicate that the furanone has a potential application for the treatment of dyslipidaemia.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The marine‐derived furanone reduces intracellular lipid accumulation in vitro by targeting LXRα and PPARα

Pang

et al. 2020

J Cellular Molecular Medi

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Nanotechnology connecting copper metabolism and tumor therapy

Dong

Zhou

2023

MedComm – Biomaterials and Applications

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Copper (Cu) is an essential trace element in the human body that is involved in the formation of several natural enzymes, such as superoxide dismutase and cyclooxygenase. Due to the high density of the outer electron cloud of Cu, which allows the transfer of multiple electrons, Cu is often used as the catalytic center in various metabolic enzymes. However, both deficiency and excessive accumulation of Cu can result in irreversible damage to cells. Therefore, strategies to regulate Cu metabolism, such as Cu exhaustion and Cu supplementation, have emerged as attractive approaches in anticancer therapy, due to the potential damages caused by Cu metabolism disorders. Notably, recent advancements in nanotechnology have enabled the development of nanomaterials that can regulate Cu metabolism, making this therapy applicable in vivo. In this review, we provide a systematic discussion of the physical and chemical properties of Cu and summarize the applications of nanotechnology in Cu metabolism‐based antitumor therapy. Finally, we outline the future directions and challenges of nano‐Cu therapy, emphasizing the scientific problems and technical bottlenecks that need to be addressed for successful clinical translation.

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Comparative subchronic toxicity of copper and a tertiary copper mixture to early life stage rainbow trout (Oncorhynchus mykiss): impacts on growth, development, and histopathology

McKay,

Baseler,

Beblow

et al. 2023

Ecotoxicology

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SREBP-1 and LXRα pathways mediated Cu-induced hepatic lipid metabolism in zebrafish Danio rerio

Cited by 43 publications

References 43 publications

The marine‐derived furanone reduces intracellular lipid accumulation in vitro by targeting LXRα and PPARα

The marine‐derived furanone reduces intracellular lipid accumulation in vitro by targeting LXRα and PPARα

Nanotechnology connecting copper metabolism and tumor therapy

Comparative subchronic toxicity of copper and a tertiary copper mixture to early life stage rainbow trout (Oncorhynchus mykiss): impacts on growth, development, and histopathology

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