Related Experiment Videos

Celecoxib decreases fatty acid synthase expression via down-regulation of c-Jun N-terminal kinase-1

Suying Lu1, Michael C Archer

  • 1Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.

Experimental Biology and Medicine (Maywood, N.J.)
|April 28, 2007
PubMed

Insights

Celecoxib, a nonsteroidal anti-inflammatory drug (NSAID), reduces fat accumulation in rats by down-regulating fatty acid synthase (FAS) through a cyclooxygenase-2 (COX-2) independent pathway involving c-Jun N-terminal kinase-1 (JNK1).

Area of Science:

  • Biochemistry
  • Pharmacology
  • Metabolic studies

Background:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) enzymes.
  • Previous studies indicated celecoxib inhibits mammary carcinogenesis and reduces fat deposition in rats.
  • This prompted an investigation into celecoxib's effects on lipid metabolism.

Purpose of the Study:

  • To determine if celecoxib affects lipid metabolism.
  • To elucidate the mechanism by which celecoxib influences fat accumulation.

Main Methods:

  • Female Sprague Dawley rats were fed a high-fat diet with or without celecoxib for 15 weeks.
  • Hepatic triglycerides and adipose tissue mass were measured.
  • Gene expression of key metabolic enzymes, including fatty acid synthase (FAS), was analyzed.
  • Prostaglandin E(2) levels and c-Jun N-terminal kinase-1 (JNK1) activity were assessed.

Main Results:

  • Celecoxib treatment significantly reduced hepatic triglycerides by 44.4% and intra-abdominal adipose tissue by 22.6%.
  • Fatty acid synthase (FAS) was significantly down-regulated in liver and adipose tissue.
  • Celecoxib's effect on fat accumulation was independent of prostaglandin E(2) levels, suggesting a COX-2 independent mechanism.
  • c-Jun N-terminal kinase-1 (JNK1) was significantly down-regulated, and JNK inhibition suppressed FAS expression in hepatocytes.

Conclusions:

  • Celecoxib suppresses fat accumulation by down-regulating fatty acid synthase (FAS).
  • This effect is mediated through a cyclooxygenase-2 (COX-2) independent pathway.
  • The mechanism involves the down-regulation of c-Jun N-terminal kinase-1 (JNK1), which in turn suppresses FAS expression.

Related Concept Videos

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 heterodimer of NF-κB...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
NF-kB-dependent Signaling Pathway02:26

NF-kB-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 heterodimer of NF-κB...