C/EBPβ in bone marrow is essential for diet induced inflammation, cholesterol balance, and atherosclerosis

Shaikh M Rahman1, Karalee C Baquero2, Mahua Choudhury3

  • 1Department of Nutritional Sciences, Texas Tech University, Lubbock, TX, USA.

Atherosclerosis
|April 14, 2016
PubMed

Insights

CCAAT/enhancer-binding protein beta (C/EBPβ) in hematopoietic cells is crucial for regulating diet-induced inflammation, hyperlipidemia, and atherosclerosis. Its absence reduces lipid levels, inflammatory responses, and aortic lesion formation.

Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Metabolic Disorders

Background:

  • Atherosclerosis is a chronic inflammatory disease linked to lipid metabolism disorders.
  • CCAAT/enhancer-binding protein beta (C/EBPβ) influences hematopoietic cell development and lipid metabolism.
  • The specific role of C/EBPβ in atherosclerotic progression remains unexamined.

Purpose of the Study:

  • To investigate the impact of hematopoietic C/EBPβ deletion on atherosclerosis development.
  • To assess the effects on hyperlipidemia, inflammatory responses, and aortic lesion formation in ApoE(-/-) mice.

Main Methods:

  • ApoE(-/-) mice were reconstituted with wild-type (WT) or C/EBPβ(-/-) bone marrow cells.
  • Mice were fed either a low-fat or high-fat/high-cholesterol diet for 11 weeks.
  • C/EBPβ was silenced in RAW264.7 macrophage cells to study foam cell formation and cytokine secretion.

Main Results:

  • Hematopoietic C/EBPβ deletion reduced blood and hepatic lipids, altering key lipid metabolism gene expression.
  • Cytokine levels were significantly reduced, and aortic lesion area decreased in mice lacking hematopoietic C/EBPβ.
  • Silencing C/EBPβ in macrophages prevented oxLDL-mediated foam cell formation and inflammatory cytokine release.

Conclusions:

  • C/EBPβ in hematopoietic cells plays a critical role in regulating diet-induced inflammation, hyperlipidemia, and atherosclerosis.
  • Targeting C/EBPβ in hematopoietic cells may offer a therapeutic strategy for atherosclerosis.
Abstract

Related Concept Videos

Cholesterol: Significance and Regulation01:29

Cholesterol: Significance and Regulation

Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
1.9K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.9K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.8K
Lipid Catabolism01:25

Lipid Catabolism

Triglycerides serve as crucial long-term energy storage molecules in microorganisms, providing a dense source of metabolic energy. Their breakdown is mediated by lipases, which hydrolyze triglycerides into glycerol and free fatty acids. Each of these components follows distinct metabolic pathways, ultimately contributing to ATP synthesis and cellular energy homeostasis.Glycerol MetabolismGlycerol, released from triglyceride hydrolysis, is phosphorylated by glycerol kinase to form...
1.3K
Inflammation01:38

Inflammation

Overview
64.0K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
10.3K