Human CEACAM1-LF regulates lipid storage in HepG2 cells via fatty acid transporter CD36

Chean, Jennifer; Chen, Charng-Jui; Gugiu, Gabriel B.; Wong, Patty; Cha, Seung; Li, Harry; Bhatticharya, Supriyo; Shively, John E.

doi:10.1016/j.jbc.2021.101311

Cited by 7 publications

(8 citation statements)

References 84 publications

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“…As shown in panel A, B and Table A1 , Esterol10 ® is able to improve the activity of PCSK9 (about 20% more than 1 µM RYR and about 2 times more than Atorvastatin, p < 0.05); on the contrary, treatment with Esterol10 ® inhibits the activity of SREBP-2, about 42% less than 1 µM RYR and about once more than Atorvastatin ( p < 0.05), showing that SREBP phosphorylation can regulate protein expression, and confirming the involvement of AMPK/SREBP signaling in treatment with Esterol10 ® . Since PCSK9 is also directly associated with CD36, which is often associated with inflammation and steatosis, it regulates LDLr levels and complex the AMPK signaling cascade which includes the SRC kinase [ 26 ]. Therefore, the same trend observed by PCSK9/SREBP, was also observed by the expressions AMPK (panel C) and SRC (panel D).…”

Section: Resultsmentioning

confidence: 99%

The Activity of Ten Natural Extracts Combined in a Unique Blend to Maintain Cholesterol Homeostasis—In Vitro Model

Ruga

Galla

Penna

et al. 2022

IJMS

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Background: Hypercholesterolemia is a major cause of cardiovascular disease and statins, the HMGCoA inhibitors, are the most prescribed drugs. Statins reduce the production of hepatic cholesterol, leading to greater expression of the LDL receptor and greater absorption of circulating LDL, reducing peripheral LDL levels. Unfortunately, statins are believed to induce myopathy and other severe diseases. To overcome this problem, safe nutraceuticals with the same activity as statins could hold great promise in the prevention and treatment of hypercholesterolemia. In this study, the anti-cholesterol efficacy of a new nutraceutical, called Esterol10®, was evaluated. Methods: HepG2 cells were used to study the biological mechanisms exerted by Esterol10® analyzing different processes involved in cholesterol metabolism, also comparing data with Atorvastatin. Results: Our results indicate that Esterol10® leads to a reduction in total hepatocyte cholesterol and an improvement in the biosynthesis of free cholesterol and bile acids. Furthermore, the anti-cholesterol activity of Esterol10® was also confirmed by the modulation of the LDL receptor and by the accumulation of lipids, as well as by the main intracellular pathways involved in the metabolism of cholesterol. Conclusions: Esterol10® is safe and effective with anti-cholesterol activity, potentially providing an alternative therapy to those based on statins for hypercholesterolemia disease.

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Section: Resultsmentioning

confidence: 99%

The Activity of Ten Natural Extracts Combined in a Unique Blend to Maintain Cholesterol Homeostasis—In Vitro Model

Ruga

Galla

Penna

et al. 2022

IJMS

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“…Because murine and human CEACAM1 may signal differently in the liver (12), we asked whether the human CEACAM1 gene could substitute for the murine Ceacam1 gene. Previously, we generated a transgenic FVB/NJ mouse expressing both murine and human CEACAM1 in which the human CEACAM1 mimicked the expression of murine CEACAM1 in the liver (13).…”

Section: Resultsmentioning

confidence: 99%

“…Lipid accumulation in NALFD is associated with altered import of nonesterified free fatty acids transported by CD36 (19) that, in turn, is associated with CEACAM1 signaling (12). Immunoblot analysis of CD36 in WT versus KO mice on an ND versus an HFD revealed lower levels of CD36 in KO mice on an ND but elevated levels in KO versus WT mice on an HFD (Supporting Information Figure S4).…”

Section: Resultsmentioning

confidence: 99%

“…Lipodomics was performed as previously described (12). A complete analysis of all lipids in the cell lines is available on request.…”

Section: Lipidomicsmentioning

confidence: 99%

“…CEACAM1 signals via two immunotyrosine inhibitory motifs in its cytoplasmic domain (11) that were recently shown to vary in their regulation between mouse and man (12). Lack of CEACAM1 inhibitory signaling in Ceacam1 −/− mice may explain the lipid accumulation in the liver that contributes to the development of obesity and NAFLD.…”

Section: Introductionmentioning

confidence: 99%

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Reversal of obesity development in Ceacam1^−/− male mice by bone marrow transplantation or introduction of the human CEACAM1 gene

Zhang

Placa

Gugiu

et al. 2022

Obesity

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ObjectiveAlthough Ceacam1−/− male mice become obese on normal chow, the effect of bone marrow transplantation or introduction of the carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1) gene has not been studied, to the knowledge of the authors.MethodsThis study analyzed Ceacam1−/− mice on normal diet or high‐fat diet (HFD), including effects of bone marrow transplantation or introduction of the CEACAM1 gene.ResultsMale Ceacam1−/− mice on normal diet versus HFD for 24 weeks gained significantly more weight than controls, and Ceacam1−/− mice aged up to 2 years had a high frequency of liver cancer. Transplantation of wild‐type bone marrow into Ceacam1−/− mice or introduction of the human CEACAM1 gene fully or partially reversed the obesity phenotype. Liver lipidomics on Ceacam1−/− versus wild‐type controls on an HFD revealed a significant increase in diacyl glycerides. An increase in fatty acid transporter CD36 levels further suggests that loss of Ceacam1 leads to a major dysregulation of free fatty acid uptake.ConclusionsCEACAM1 expression in both the liver and immune cells regulates obesity and lipid storage pathways in the liver. Bone marrow reconstitution of the immune system or introduction of the human CEACAM1 gene can fully or partially reverse the phenotype.

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Regulation of lipid storage and inflammation in the liver by CEACAM1

Najjar,

Shively

2024

Eur J Clin Investigation

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This review focuses on a special aspect of hepatic lipid storage and inflammation that occurs during nutritional excess in obesity. Mounting evidence supports that prolonged excess fatty acid (FA) uptake in the liver is strongly associated with hepatic lipid storage and inflammation and that the two processes are closely linked by a homeostatic mechanism. There is also strong evidence that bacterial lipids may enter the gut by a common mechanism with lipid absorption and that there is a set point to determine when their uptake triggers an inflammatory response in the liver. In fact, the progression from high uptake of FAs in the liver resulting in Metabolic dysfunction‐associated steatotic liver disease (MASLD) to the development of the more serious Metabolic dysfunction‐associated steatohepatitis (MASH) depends on the degree of inflammation and its progression from an acute to a chronic state. Thus, MASLD/MASH implicates both excess fatty acids and progressive inflammation in the aetiology of liver disease. We start the discussion by introduction of CD36, a major player in FA and lipopolysaccharide (LPS) uptake in the duodenum, liver and adipose tissue. We will then introduce CEACAM1, a major player in the regulation of hepatic de novo lipogenesis and the inflammatory response in the liver, and its dual association with CD36 in enterocytes and hepatocytes. We conclude that CEACAM1 and CD36 together regulate lipid droplet formation and inflammation in the liver.

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Human CEACAM1-LF regulates lipid storage in HepG2 cells via fatty acid transporter CD36

Cited by 7 publications

References 84 publications

The Activity of Ten Natural Extracts Combined in a Unique Blend to Maintain Cholesterol Homeostasis—In Vitro Model

The Activity of Ten Natural Extracts Combined in a Unique Blend to Maintain Cholesterol Homeostasis—In Vitro Model

Reversal of obesity development in Ceacam1^−/− male mice by bone marrow transplantation or introduction of the human CEACAM1 gene

Regulation of lipid storage and inflammation in the liver by CEACAM1

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Human CEACAM1-LF regulates lipid storage in HepG2 cells via fatty acid transporter CD36

Cited by 7 publications

References 84 publications

The Activity of Ten Natural Extracts Combined in a Unique Blend to Maintain Cholesterol Homeostasis—In Vitro Model

The Activity of Ten Natural Extracts Combined in a Unique Blend to Maintain Cholesterol Homeostasis—In Vitro Model

Reversal of obesity development in Ceacam1−/− male mice by bone marrow transplantation or introduction of the human CEACAM1 gene

Regulation of lipid storage and inflammation in the liver by CEACAM1

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Reversal of obesity development in Ceacam1^−/− male mice by bone marrow transplantation or introduction of the human CEACAM1 gene