Policosanol alleviates hepatic lipid accumulation by regulating bile acids metabolism in C57BL6/mice through AMPK–FXR–TGR5 cross‐talk

Zhai, Zhe; Niu, Kai-Yang; Liu, Huiping; Lin, Chi-Chung; Tu, Yue; Liu, Yichun; Cai, Liang; Kexian, Ouyang; Liu, Jianping

doi:10.1111/1750-3841.15951

Cited by 16 publications

(19 citation statements)

References 44 publications

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Section: Introductionmentioning

confidence: 99%

“…1 Over the past few decades, some bile acids have been used as nutrients, feed additives, and clinical therapeutic supplements owing to their roles in blood lipid regulation, intestinal injury recovery, and immune enhancement. [2][3][4][5] Intestinal epithelial homeostasis relies on the balance between cell proliferation and cell death. 10 Cell proliferation is essential for driving intestinal epithelial renewal and injury repair.…”

Section: Introductionmentioning

confidence: 99%

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Taurochenodeoxycholic acid inhibits intestinal epithelial cell proliferation and induces apoptosis independent of the farnesoid X receptor

et al. 2023

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Taurochenodeoxycholic acid inhibits intestinal epithelial cell proliferation and induces apoptosis independent of the farnesoid X receptor

et al. 2023

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“…Studies have shown that activation of AMPK inhibits the transcriptional activity of FXR and downregulates SHP. 35 , 36 Thus, the changes we observed in the FXR-SHP-CYP7A1 pathway may be attributed to activation of AMPK by NgBR overexpression. Taken together, we determined the mechanism by which NgBR regulates AMPKα activation and the NgBR overexpression-activated SR-BI and bile acid synthesis pathways may be regulated by AMPKα activation.…”

Section: Discussionmentioning

confidence: 80%

Overexpression of NgBR inhibits high-fat diet–induced atherosclerosis in ApoE-deficiency mice

Gong

Wang

et al. 2023

Hepatology Communications

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Background: Hyperlipidemia (hypercholesterolemia and/or hypertriglyceridemia) is a risk factor for atherosclerosis. Nogo-B receptor (NgBR) plays important roles in hepatic steatosis and cholesterol transport. However, the effect of NgBR overexpression on atherosclerosis remains unknown. Materials and Methods: Apolipoprotein E deficient (ApoE -/- ) mice infected with adeno-associated virus (AAV)-NgBR expression vector were fed a high-fat diet for 12 weeks, followed by determination of atherosclerosis and the involved mechanisms. Results: We determined that high expression of NgBR by AAV injection mainly occurs in the liver and it can substantially inhibit en face and aortic root sinus lesions. NgBR overexpression also reduced levels of inflammatory factors in the aortic root and serum, and levels of cholesterol, triglyceride, and free fatty acids in the liver and serum. Mechanistically, NgBR overexpression increased the expression of scavenger receptor type BI and the genes for bile acid synthesis, and decreased the expression of cholesterol synthesis genes by reducing sterol regulatory element-binding protein 2 maturation in the liver, thereby reducing hypercholesterolemia. In addition, NgBR overexpression activated AMP-activated protein kinase α via the Ca 2+ signaling pathway, which inhibited fat synthesis and improved hypertriglyceridemia. Conclusions: Taken together, our study demonstrates that overexpression of NgBR enhanced cholesterol metabolism and inhibited cholesterol/fatty acid synthesis to reduce hyperlipidemia, and reduced vascular inflammation, thereby inhibiting atherosclerosis in ApoE -/- mice. Our study indicates that NgBR might be a potential target for atherosclerosis treatment.

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“…It was reported that the prevention of hepatic lipid accumulation in obese mice can be achieved through many ways. For instance, policosanol attenuated hepatic lipid accumulation in mice by regulating AMPK-FXR-TGR5 cross-talk ( 43 ). In addition, Han et al have testified that the depletion of gut microbiota could suppress hepatic lipid accumulation in HFD-fed mice ( 44 ).…”

Section: Discussionmentioning

confidence: 99%

Cathepsin S inhibitor reduces high-fat-induced adipogenesis, inflammatory infiltration, and hepatic lipid accumulation in obese mice

Zheng¹,

Zhuang²,

Zhang³

et al. 2022

Ann Transl Med

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Background: Obesity, which results from a caloric intake and energy expenditure imbalance, is highly prevalent worldwide. Cathepsin S (CTSS), which is a cysteine protease, is elevated in obesity and may regulate a variety of physiological processes. This study sought to investigate the functional role of CTSS in obesity.Methods: Mice were administrated 60 mg/kg of RO5444101 in vivo and fed a high-fat diet (HFD) to induce obesity. The weights of the mice fed a normal-chow diet and a HFD were measured. The expression levels of total triglycerides (TG), total cholesterol (TC), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and monocyte chemoattractant protein-1 (MCP-1) were assessed using appropriate corresponding assay kits. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to estimate the messenger ribonucleic acid (mRNA) expression of CTSS in the serum and the release of M1-and M2-type cytokines, and western blot was used to measure the phosphorylated-nuclear factor kappaB (NF-kappaB) p65 and NF-κB p65 proteins. The mRNA and protein expressions of sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FASN), leptin, and adiponectin were also evaluated by RT-qPCR and western blot. Further, hematoxylin and eosin (H&E), immunohistochemical, and red oil O staining were employed to detect the pathological changes of the epididymal white adipose tissue (eWAT), the macrophage infiltration in the eWAT, and lipid accumulation, respectively.Results: We found that CTSS was elevated in the plasma, visceral adipose, and liver tissues of the obese mice. After the administration of 60 mg/kg of RO5444101, the weight of the obese mice decreased, insulin resistance was inhibited, and adipocyte formation was suppressed. The CTSS inhibitor also decreased the level of macrophage infiltration in the eWAT, MCP-1 expression, and the release of M1-and M2type cytokines in the HFD-induced mice. The CTSS inhibitor appeared to improve the hepatic function parameters and lipid accumulation of the HFD-induced mice. The CTSS inhibitor also appeared to improve the inflammatory damage in the HFD-induced mice.Conclusions: CTSS inhibitor helped to protect against HFD-induced adipogenesis, inflammatory infiltration, and hepatic lipid accumulation in obese mice.

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Policosanol alleviates hepatic lipid accumulation by regulating bile acids metabolism in C57BL6/mice through AMPK–FXR–TGR5 cross‐talk

Cited by 16 publications

References 44 publications

Taurochenodeoxycholic acid inhibits intestinal epithelial cell proliferation and induces apoptosis independent of the farnesoid X receptor

Taurochenodeoxycholic acid inhibits intestinal epithelial cell proliferation and induces apoptosis independent of the farnesoid X receptor

Overexpression of NgBR inhibits high-fat diet–induced atherosclerosis in ApoE-deficiency mice

Cathepsin S inhibitor reduces high-fat-induced adipogenesis, inflammatory infiltration, and hepatic lipid accumulation in obese mice

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