Related Experiment Video

Updated: May 23, 2026

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells
07:22

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells

Published on: March 28, 2013

Improved insulin sensitivity after treatment with PPARγ and PPARα ligands is mediated by genetically modulated

Neda Rasouli1, Philip A Kern, Steven C Elbein

  • 1Department of Internal Medicine, Division of Endocrinology, University of Colorado Denver, Aurora, USA.

Pharmacogenetics and Genomics
|March 23, 2012
PubMed
Abstract

Insights

PPARγ agonists, with or without PPARα agonists, alter gene expression in adipose tissue, improving insulin sensitivity. Genetic variations in these PPAR-regulated genes influence glucose levels and treatment response.

Area of Science:

  • Metabolic research
  • Genomics
  • Pharmacology

Background:

  • Peroxisomal proliferator-activated receptor gamma (PPARγ) and PPAR alpha (PPARα) agonists are used to improve insulin sensitivity.
  • Understanding their effects on gene expression in adipose tissue and skeletal muscle is crucial for optimizing treatment.

Purpose of the Study:

  • To define the effects of PPARγ and PPARα agonist therapy on gene expression in adipose and skeletal muscle tissues in relation to insulin sensitivity.
  • To investigate the role of genetic polymorphisms in PPAR ligand-modulated genes in transcriptional regulation and glucose homeostasis.

Main Methods:

  • Genome-wide transcript profiles and metabolic phenotypes were analyzed before and after 10 weeks of pioglitazone (PPARγ agonist) and fenofibrate (PPARα agonist) monotherapy or combination therapy in patients with impaired glucose tolerance.
  • Genome-wide association data and adipose tissue expression quantitative trait loci (eQTL) data were used to assess the functional role of single nucleotide polymorphisms (SNPs) in PPAR ligand-modulated genes.

Main Results:

  • PPARγ agonists, alone or combined with PPARα agonists, upregulated genes involved in metabolic pathways (TCA cycle, fatty acid metabolism, insulin signaling) and downregulated immune/inflammatory genes in adipose tissue.
  • Few significant changes were observed in skeletal muscle gene expression.
  • Combined therapy showed specific enrichment of genes in propanoate metabolism and fatty acid elongation in adipose tissue.
  • SNPs in 22 PPAR ligand-modulated genes were associated with fasting plasma glucose, and 28 transcripts were regulated by local genetic factors in adipose tissue.

Conclusions:

  • Transcriptional changes in adipose tissue mediate the insulin-sensitizing effects of PPARγ agonist monotherapy or combination therapy with PPARα agonists.
  • Genetic variations (SNPs) in PPAR-modulated genes are key factors influencing inter-individual responses to thiazolidinedione and fenofibrate treatments and may impact glucose homeostasis.

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

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice11:10

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

Published on: November 16, 2011

Related Concept Videos

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...
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
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:
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...
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 cells.
Two...
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...