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

Li, Ting; Hu, Shumei; Pang, Xiaoyan; Wang, Junfeng; Yin, Jiayu; Li, Fahui; Wang, Jin; Yang, Xiaoqian; Xia, Bin; Liu, Yonghong; Song, Weiguo; Guo, Shoudong

doi:10.1111/jcmm.15012

Cited by 30 publications

(31 citation statements)

References 52 publications

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“…Since the liver is an important organ for TG synthesis, we found that Pparα was significantly increased after high-dose DEX treatment in liver. Pparα stimulated fatty acid beta oxidation and promoted the metabolism of NEFA and TG [33,34]. The RXRA/ Pparα heterodimer is required for Pparα transcriptional activity on fatty acid oxidation genes such as ACOX1.…”

Section: Discussionmentioning

confidence: 99%

“…We also found treatment with high-dose DEX significantly decreased the levels of serum TGs and NEFAs in tumor-bearing mice (Figure 5B,C). Proliferator-activated receptor-alpha (Pparα) stimulated fatty acid beta oxidation and promoted the metabolism of NEFAs and TGs [33,34]. The retinoid X receptor alpha (RXRA)/ Pparα heterodimer is required for Pparα transcriptional activity on fatty acid oxidation genes such as peroxisomal acyl-coenzyme A oxidase 1 (ACOX1).…”

Section: High-dose Dex Treatment Significantly Reduced Serum Triglycementioning

confidence: 99%

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High-Dose Dexamethasone Manipulates the Tumor Microenvironment and Internal Metabolic Pathways in Anti-Tumor Progression

Hua

et al. 2020

IJMS

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High-dose dexamethasone (DEX) is used to treat chemotherapy-induced nausea and vomiting or to control immunotherapy-related autoimmune diseases in clinical practice. However, the underlying mechanisms of high-dose DEX in tumor progression remain unaddressed. Therefore, we explored the effects of high-dose DEX on tumor progression and the potential mechanisms of its anti-tumor function using immunohistochemistry, histological examination, real-time quantitative PCR (qPCR), and Western blotting. Tumor volume, blood vessel invasion, and levels of the cell proliferation markers Ki67 and c-Myc and the anti-apoptotic marker Bcl2 decreased in response to high-dose DEX. However, the cell apoptosis marker cleaved caspase 3 increased significantly in mice treated with 50 mg/kg DEX compared with controls. Some genes associated with immune responses were significantly downregulated following treatment with 50 mg/kg DEX e.g., Cxcl9, Cxcl10, Cd3e, Gzmb, Ifng, Foxp3, S100a9, Arg1, and Mrc1. In contrast, the M1-like tumor-associated macrophages (TAMs) activation marker Nos2 was shown to be increased. Moreover, the expression of peroxisome proliferator-activated receptors α and γ (Pparα and Pparg, respectively) was shown to be significantly upregulated in livers or tumors treated with DEX. However, high-dose DEX treatment decreased the expression of glucose and lipid metabolic pathway-related genes such as glycolysis-associated genes (Glut1, Hk2, Pgk1, Idh3a), triglyceride (TG) synthesis genes (Gpam, Agpat2, Dgat1), exogenous free fatty acid (FFA) uptake-related genes (Fabp1, Slc27a4, and CD36), and fatty acid oxidation (FAO) genes (Acadm, Acaa1, Cpt1a, Pnpla2). In addition, increased serum glucose and decreased serum TG and non-esterified fatty acid (NEFA) were observed in DEX treated-xenografted tumor mice. These findings indicate that high-dose DEX-inhibited tumor progression is a complicated process, not only activated by M1-like TAMs, but also decreased by the uptake and consumption of glucose and lipids that block the raw material and energy supply of cancer cells. Activated M1-like TAMs and inefficient glucose and lipid metabolism delayed tumor cell growth and promoted apoptosis. These findings have important implications for the application of DEX combined with drugs that target key metabolism pathways for tumor therapy in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Section: High-dose Dex Treatment Significantly Reduced Serum Triglycementioning

confidence: 99%

High-Dose Dexamethasone Manipulates the Tumor Microenvironment and Internal Metabolic Pathways in Anti-Tumor Progression

Hua

et al. 2020

IJMS

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“…In addition to the above, some other marine products exhibit strong lipid-lowering effects. The furanone isolated from Fungus setosphaeria sp SCSIO41009 was shown to significantly reduce lipid accumulation in ox-LDL induced RAW 264.7 cells [118]. It was shown that the cellular models used in this study demonstrated a significant reduction in its TG content, and an increase in the expression of PPAR-alpha and ABC transporters.…”

Section: Secondary Metabolites and Other Marine-derived Productsmentioning

confidence: 66%

“…In HepG2 cells, furanone efficaciously reduced the lipid accumulation caused by oleic acid, improved LDLR, ABCG5, ABCG8 and PPAR-alpha expression and reduced the expression of SREBP-2. Subsequent results showed that LXR-alpha and PPAR-alpha could be targeted to exert their hypolipidemic effect [118]. Isolated from Fungus xylaria sp.…”

Section: Secondary Metabolites and Other Marine-derived Productsmentioning

confidence: 99%

Advances in the Study of Marine Products with Lipid-Lowering Properties

et al. 2020

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With twice the number of cancer’s deaths, cardiovascular diseases have become the leading cause of death worldwide. Atherosclerosis, in particular, is a progressive, chronic inflammatory cardiovascular disease caused by persistent damage to blood vessels due to elevated cholesterol levels and hyperlipidemia. This condition is characterized by an increase in serum cholesterol, triglycerides, and low-density lipoprotein, and a decrease in high-density lipoprotein. Although existing therapies with hypolipidemic effects can improve the living standards of patients with cardiovascular diseases, the drugs currently used in clinical practice have certain side effects, which insists on the need for the development of new types of drugs with lipid-lowering effects. Some marine-derived substances have proven hypolipidemic activities with fewer side effects and stand as a good alternative for drug development. Recently, there have been thousands of studies on substances with lipid-lowering properties of marine origin, and some are already implemented in clinical practice. Here, we summarize the active components of marine-derived products having a hypolipidemic effect. These active constituents according to their source are divided into algal, animal, plant and microbial and contribute to the development and utilization of marine medicinal products with hypolipidemic effects.

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“…Cells were cultured as the previously described method [ 18 ]. At day one, cells were set in six-well dishes at a density of 2 × 10 5 cells per well.…”

Section: Methodsmentioning

confidence: 99%

Polysaccharide CM1 from Cordyceps militaris hinders adipocyte differentiation and alleviates hyperlipidemia in LDLR(+/−) hamsters

Yin

Shen

et al. 2021

Lipids Health Dis

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Background Cordyceps militaris is cultured widely as an edible mushroom and accumulating evidence in mice have demonstrated that the polysaccharides of Cordyceps species have lipid-lowering effects. However, lipid metabolism in mice is significantly different from that in humans, making a full understanding of the mechanisms at play critical. Methods After 5 months, the hamsters were weighed and sampled under anesthesia after overnight fasting. The lipid-lowering effect and mechanisms of the polysaccharide CM1 was investigated by cellular and molecular technologies. Furthermore, the effect of the polysaccharide CM1 (100 μg/mL) on inhibiting adipocyte differentiation was investigated in vitro. Results CM1, a polysaccharide from C. militaris, significantly decreased plasma total cholesterol, triglyceride and epididymal fat index in LDLR(+/−) hamsters, which have a human-like lipid profile. After 5 months’ administration, CM1 decreased the plasma level of apolipoprotein B48, modulated the expression of key genes and proteins in liver, small intestine, and epididymal fat. CM1 also inhibited preadipocyte differentiation in 3T3-L1 cells by downregulating the key genes involved in lipid droplet formation. Conclusions The polysaccharide CM1 lowers lipid and adipocyte differentiation by several pathways, and it has potential applications for hyperlipidemia prevention.

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

Cited by 30 publications

References 52 publications

High-Dose Dexamethasone Manipulates the Tumor Microenvironment and Internal Metabolic Pathways in Anti-Tumor Progression

High-Dose Dexamethasone Manipulates the Tumor Microenvironment and Internal Metabolic Pathways in Anti-Tumor Progression

Advances in the Study of Marine Products with Lipid-Lowering Properties

Polysaccharide CM1 from Cordyceps militaris hinders adipocyte differentiation and alleviates hyperlipidemia in LDLR(+/−) hamsters

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