Related Experiment Video

Updated: Jul 16, 2025

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
09:41

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro

Published on: March 17, 2023

2.9K

Inflammation-induced nitric oxide suppresses PPARα expression and function via downregulation of Sp1 transcriptional

Jungin Kwon1, Yumeko Aoki1, Haruya Takahashi1

  • 1Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji 611-0011, Japan.

Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms
|September 22, 2023
PubMed

Insights

Nitric oxide (NO) suppresses peroxisome proliferator-activated receptor alpha (PPARα) gene expression in adipocytes by inhibiting Sp1 activity. This mechanism may explain reduced PPARα in obesity and inflammation.

Area of Science:

  • Molecular biology
  • Metabolic regulation
  • Cell signaling

Background:

  • Peroxisome proliferator-activated receptor alpha (PPARα) activation treats hyperlipidemia.
  • PPARα gene expression is reduced in adipose tissue during obesity, but mechanisms are unclear.
  • Nitric oxide (NO) is implicated in inflammatory and metabolic processes.

Purpose of the Study:

  • To elucidate the molecular mechanism by which NO affects PPARα gene expression in adipocytes.
  • To investigate the role of Sp1 (specificity protein 1) in NO-mediated PPARα regulation.
  • To explore the relevance of this mechanism in inflammatory conditions and obesity.

Main Methods:

  • In vitro studies using 10T1/2 adipocytes treated with NO donors or lipopolysaccharide (LPS).
  • In vivo studies using acute and chronic inflammation mouse models.
  • Pharmacological inhibition of nitric oxide synthase 2 (NOS2) and endoplasmic reticulum (ER) stress.
  • Promoter mutagenesis and chromatin immunoprecipitation (ChIP) assays to assess Sp1 binding.

Main Results:

  • NO suppressed PPARα mRNA expression in adipocytes and white adipose tissue (WAT) of mice.
  • NOS2 inhibition attenuated NO-induced suppression of PPARα.
  • ER stress inhibitors partially rescued NO-induced repression of PPARα.
  • NO reduced Sp1 binding to the PPARα promoter, potentially via decreased Sp1 expression.

Conclusions:

  • Nitric oxide suppresses PPARα gene expression in adipocytes by inhibiting Sp1 transcriptional activity.
  • This NO-mediated pathway provides a molecular mechanism for PPARα downregulation in WAT during inflammation and potentially obesity.
  • Targeting NO signaling could offer therapeutic strategies for metabolic disorders associated with PPARα dysregulation.
Keywords:
Adipose tissueEndoplasmic reticulum stressInflammationNitric oxidePPARαSp1

More Related Videos

An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function09:20

An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function

Published on: May 4, 2021

3.7K
Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis08:34

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis

Published on: June 3, 2016

15.1K

Related Concept Videos

Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
5.1K
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.4K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.7K
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...
7.5K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
Adrenergic Receptors: β Subtype01:26

Adrenergic Receptors: β Subtype

β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
1.7K