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Published on: November 10, 2017
CREBH regulation of lipid metabolism through multifaceted functions that improve arteriosclerosis
Yoshimi Nakagawa1, Takashi Matsuzaka2,3, Hitoshi Shimano2
1Division of Complex Biosystem Research, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
Insights
Cyclic adenosine monophosphate-responsive element-binding protein H (CREBH) enhances the clearance of remnant lipoproteins, reducing plaque formation and lowering plasma triglycerides. This improves HDL-cholesterol levels and promotes cardiovascular health.
Area of Science:
- Metabolic regulation
- Lipid metabolism
- Cardiovascular disease research
Background:
- Lipoprotein lipase (LPL) activity is crucial for hydrolyzing triglyceride-rich lipoproteins.
- Remnant lipoproteins contribute to atherogenic plaque formation.
- Apolipoproteins, including ApoE and ApoC3, play key roles in remnant particle clearance.
Purpose of the Study:
- To investigate the role of CREBH in regulating LPL activity and lipoprotein metabolism.
- To understand how CREBH influences the clearance of remnant lipoproteins.
- To determine the impact of CREBH on cardiovascular risk factors like plasma triglycerides and HDL-cholesterol.
Main Methods:
- The study likely involved molecular biology techniques to assess CREBH activity and its downstream targets.
- Analysis of apolipoprotein expression and lipoprotein receptor levels.
- Measurement of plasma lipid profiles, including triglycerides and HDL-cholesterol.
Main Results:
- CREBH activation leads to increased LPL activity.
- CREBH modulates apolipoprotein levels, enhancing remnant particle clearance via ApoE and reducing ApoC3.
- CREBH upregulates VLDL receptor (VLDLR) and LDL receptor-related protein 1 (LRP1) expression.
- CREBH induces fibroblast growth factor 21 (FGF21) secretion, lowering plasma triglycerides.
- CREBH promotes ApoA1 production, increasing HDL-cholesterol.
Conclusions:
- CREBH plays a significant role in promoting the clearance of atherogenic remnant lipoproteins.
- CREBH activation reduces atherogenic plaque area and improves lipid profiles.
- CREBH represents a potential therapeutic target for managing dyslipidemia and cardiovascular disease.
Abstract:
Cyclic adenosine monophosphate-responsive element-binding protein H (CREBH) activates lipoprotein lipase (LPL) activity by modulating apolipoproteins. Activated LPL hydrolyzes triglyceride-rich lipoproteins, such as very low-density lipoprotein (VLDL) and chylomicrons, resulting in remnant lipoproteins. CREBH increases apolipoprotein E (ApoE), a ligand that mediates the clearance of remnant particles and reduces ApoC3, which interferes with remnant clearance. CREBH also improves VLDL receptor (VLDLR) and LDL receptor-related protein 1 (LRP1) protein that mediates remnant clearance. Therefore, CREBH promotes the clearance of remnant particles from the blood, decreasing the atherogenic plaque area. CREBH induces the secretion of fibroblast growth factor 21 (FGF21) into the blood, decreasing plasma triglyceride. CREBH produces ApoA1 and so increases plasma HDL-cholesterol levels.
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