scholarly journals CREBH Systemically Regulates Lipid Metabolism by Modulating and Integrating Cellular Functions

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3204
Author(s):  
Yoshimi Nakagawa ◽  
Masaya Araki ◽  
Song-iee Han ◽  
Yuhei Mizunoe ◽  
Hitoshi Shimano
Keyword(s):  
Small Intestine ◽  
Lipid Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Homeostasis ◽  
Transcriptional Level ◽  
Cellular Functions ◽  
Density Lipoprotein Receptor ◽  
Element Binding Protein ◽  
Severe Atherosclerosis

Cyclic AMP-responsive element-binding protein H (CREBH, encoded by CREB3L3) is a membrane-bound transcriptional factor expressed in the liver and small intestine. The activity of CREBH is regulated not only at the transcriptional level but also at the posttranslational level. CREBH governs triglyceride metabolism in the liver by controlling gene expression, with effects including the oxidation of fatty acids, lipophagy, and the expression of apolipoproteins related to the lipoprotein lipase activation and suppression of lipogenesis. The activation and functions of CREBH are controlled in response to the circadian rhythm. On the other hand, intestinal CREBH downregulates the absorption of lipids from the diet. CREBH deficiency in mice leads to severe hypertriglyceridemia and fatty liver in the fasted state and while feeding a high-fat diet. Therefore, when crossing CREBH knockout (KO) mice with an atherosclerosis model, low-density lipoprotein receptor KO mice, these mice exhibit severe atherosclerosis. This phenotype is seen in both liver- and small intestine-specific CREBH KO mice, suggesting that CREBH controls lipid homeostasis in an enterohepatic interaction. This review highlights that CREBH has a crucial role in systemic lipid homeostasis to integrate cellular functions related to lipid metabolism.

scholarly journals Trypanosoma cruziInfection and Host Lipid Metabolism

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Qianqian Miao ◽  
Momar Ndao
Keyword(s):  
Lipid Metabolism ◽  
Metabolic Pathways ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Homeostasis ◽  
Low Density ◽  
Host Interactions ◽  
Density Lipoprotein Receptor ◽  
The Status ◽  
Potential Impact

Trypanosoma cruziis the causative agent of Chagas disease. Approximately 8 million people are thought to be affected worldwide. Several players in host lipid metabolism have been implicated inT. cruzi-host interactions in recent research, including macrophages, adipocytes, low density lipoprotein (LDL), low density lipoprotein receptor (LDLR), and high density lipoprotein (HDL). All of these factors are required to maintain host lipid homeostasis and are intricately connected via several metabolic pathways. We reviewed the interaction ofT. cruziwith each of the relevant host components, in order to further understand the roles of host lipid metabolism inT. cruziinfection. This review sheds light on the potential impact ofT. cruziinfection on the status of host lipid homeostasis.

scholarly journals Two Weeks Of Western Diet Disrupts Liver Molecular Markers Of Cholesterol Metabolism In Rat

2020 ◽  
Author(s):  
Roxane St-Amand ◽  
Emilienne T. Ngo Sock ◽  
Samantha Quinn ◽  
Jean-Marc Lavoie ◽  
David H. St-Pierre
Keyword(s):  
Total Cholesterol ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Plasma Total Cholesterol ◽  
Cholesterol Levels ◽  
Density Lipoprotein Receptor ◽  
Element Binding Protein

Abstract Background: The present study was designed to test the hypothesis that in the liver, excessive fat accumulation impairs cholesterol metabolism mainly by altering the low-density lipoprotein-receptor (LDL-R) pathway. Method: Young male Wistar rats were fed standard (SD), high fat (HFD; 60% kcal) or Western (WD; 40% fat + 35% sucrose (17.5% fructose)) diets for 2 or 6 weeks. Results: Weight gain (~ 40g) was observed only following 6 weeks of the obesogenic diets (P < 0.01). Compared to the 2-week treatment, obesogenic diets tripled fat pad weight (~ 20 vs 7 g) after 6 weeks. Hepatic triglyceride (TG) levels were greater in response to both the WD and HFD compared to the SD (P < 0.01) at 2 and 6 weeks and their concentrations were greater (P < 0.05) in WD than HFD at 2 weeks. Plasma total cholesterol levels were higher (P < 0.05) in animals submitted to WD. After 2 and 6 weeks, liver expression of LDL-R, proprotein convertase subtilisin/kexin 9 (PCSKk9) and sterol regulatory element binding protein 2 (SREBP2), involved in LDL-cholesterol uptake, was lower in animals submitted to WD than in others treated with HFD or SD (P < 0.01). Similarly, low-density lipoprotein-receptor-related protein 1 (LRP1) and acyl-CoA cholesterol acyltransferase-2 (ACAT-2) mRNA levels were lower (P < 0.01) among WD compared to SD-fed rats. Expression of the gene coding the main regulator of endogenous cholesterol synthesis, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoAR) was reduced in response to WD compared to SD and HFD at 2 (P < 0.001) and 6 (P < 0.05) weeks. Being enriched in fructose, the WD strongly promoted the expression of carbohydrate-response element binding protein (ChREBP) and acetyl-CoA carboxylase (ACC), two key regulators of de novo lipogenesis. Conclusion: These results show that the WD promptly increased TG levels in the liver by potentiating fat storage. This impaired the pathway of hepatic cholesterol uptake via the LDL-R axis, promoting a rapid increase in plasma total cholesterol levels. These results indicate that liver fat content is a factor involved in the regulation of plasma cholesterol.

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