Roles of PPAR delta in lipid absorption and metabolism: a new target for the treatment of type 2 diabetes

Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors exerting several functions in development and metabolism. PPARα, activated by polyunsaturated fatty acids and fibrates, is implicated in regulation of lipid metabolism, lipoprotein synthesis and metabolism...

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Published inBiochimica et biophysica acta Vol. 1740; no. 2; pp. 313 - 317
Main Authors Luquet, Serge, Gaudel, Celine, Holst, Dorte, Lopez-Soriano, Joaquin, Jehl-Pietri, Chantal, Fredenrich, Alexandre, Grimaldi, Paul A.
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 30.05.2005
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Abstract Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors exerting several functions in development and metabolism. PPARα, activated by polyunsaturated fatty acids and fibrates, is implicated in regulation of lipid metabolism, lipoprotein synthesis and metabolism and inflammatory response in liver and other tissues. PPARγ plays important roles in regulation of proliferation and differentiation of several cell types, including adipose cells. Its activation by thiazolidinediones results in insulin sensibilization and antidiabetic action. Until recently, the physiological functions of PPARδ remain elusive. The utilization of specific agonists and of appropriate cellular and animal models revealed that PPARδ has an important role in metabolic adaptation of several tissues to environmental changes. Treatment of obese animals by specific PPARδ agonists results in normalization of metabolic parameters and reduction of adiposity. The nuclear receptor appeared to be implicated in the regulation of fatty acid burning capacities of skeletal muscle and adipose tissue by controlling the expression of genes involved in fatty acid uptake, β-oxidation and energy uncoupling. PPARδ is also implicated in the adaptive metabolic response of skeletal muscle to endurance exercise by controlling the number of oxidative myofibers. Given the results obtained with animal models, PPARδ agonists may have therapeutic usefulness in metabolic syndrome by increasing fatty acid consumption in skeletal muscle and adipose tissue.
AbstractList Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors exerting several functions in development and metabolism. PPARα, activated by polyunsaturated fatty acids and fibrates, is implicated in regulation of lipid metabolism, lipoprotein synthesis and metabolism and inflammatory response in liver and other tissues. PPARγ plays important roles in regulation of proliferation and differentiation of several cell types, including adipose cells. Its activation by thiazolidinediones results in insulin sensibilization and antidiabetic action. Until recently, the physiological functions of PPARδ remain elusive. The utilization of specific agonists and of appropriate cellular and animal models revealed that PPARδ has an important role in metabolic adaptation of several tissues to environmental changes. Treatment of obese animals by specific PPARδ agonists results in normalization of metabolic parameters and reduction of adiposity. The nuclear receptor appeared to be implicated in the regulation of fatty acid burning capacities of skeletal muscle and adipose tissue by controlling the expression of genes involved in fatty acid uptake, β-oxidation and energy uncoupling. PPARδ is also implicated in the adaptive metabolic response of skeletal muscle to endurance exercise by controlling the number of oxidative myofibers. Given the results obtained with animal models, PPARδ agonists may have therapeutic usefulness in metabolic syndrome by increasing fatty acid consumption in skeletal muscle and adipose tissue.
Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors exerting several functions in development and metabolism. PPARalpha, activated by polyunsaturated fatty acids and fibrates, is implicated in regulation of lipid metabolism, lipoprotein synthesis and metabolism and inflammatory response in liver and other tissues. PPARgamma plays important roles in regulation of proliferation and differentiation of several cell types, including adipose cells. Its activation by thiazolidinediones results in insulin sensibilization and antidiabetic action. Until recently, the physiological functions of PPARdelta remain elusive. The utilization of specific agonists and of appropriate cellular and animal models revealed that PPARdelta has an important role in metabolic adaptation of several tissues to environmental changes. Treatment of obese animals by specific PPARdelta agonists results in normalization of metabolic parameters and reduction of adiposity. The nuclear receptor appeared to be implicated in the regulation of fatty acid burning capacities of skeletal muscle and adipose tissue by controlling the expression of genes involved in fatty acid uptake, beta-oxidation and energy uncoupling. PPARdelta is also implicated in the adaptive metabolic response of skeletal muscle to endurance exercise by controlling the number of oxidative myofibers. Given the results obtained with animal models, PPARdelta agonists may have therapeutic usefulness in metabolic syndrome by increasing fatty acid consumption in skeletal muscle and adipose tissue.
Author Gaudel, Celine
Jehl-Pietri, Chantal
Lopez-Soriano, Joaquin
Fredenrich, Alexandre
Grimaldi, Paul A.
Luquet, Serge
Holst, Dorte
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  givenname: Serge
  surname: Luquet
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– sequence: 2
  givenname: Celine
  surname: Gaudel
  fullname: Gaudel, Celine
– sequence: 3
  givenname: Dorte
  surname: Holst
  fullname: Holst, Dorte
– sequence: 4
  givenname: Joaquin
  surname: Lopez-Soriano
  fullname: Lopez-Soriano, Joaquin
– sequence: 5
  givenname: Chantal
  surname: Jehl-Pietri
  fullname: Jehl-Pietri, Chantal
– sequence: 6
  givenname: Alexandre
  surname: Fredenrich
  fullname: Fredenrich, Alexandre
– sequence: 7
  givenname: Paul A.
  surname: Grimaldi
  fullname: Grimaldi, Paul A.
  email: grimaldi@unice.fr
BackLink https://www.ncbi.nlm.nih.gov/pubmed/15949697$$D View this record in MEDLINE/PubMed
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Keywords Type 2 diabetes
Obesity
PPAR
Metabolic syndrome
Fatty acid
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Snippet Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors exerting several functions in development and metabolism. PPARα,...
Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors exerting several functions in development and metabolism....
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StartPage 313
SubjectTerms Adipose Tissue - metabolism
Animals
Carrier Proteins - metabolism
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - metabolism
Fatty acid
Fatty Acid-Binding Proteins
Fatty Acids - metabolism
Humans
Lipid Metabolism
Metabolic syndrome
Metabolic Syndrome - drug therapy
Mitochondrial Trifunctional Protein
Multienzyme Complexes - metabolism
Muscle, Skeletal - metabolism
Obesity
PPAR
PPAR delta - agonists
PPAR delta - metabolism
Type 2 diabetes
Title Roles of PPAR delta in lipid absorption and metabolism: a new target for the treatment of type 2 diabetes
URI https://dx.doi.org/10.1016/j.bbadis.2004.11.011
https://www.ncbi.nlm.nih.gov/pubmed/15949697
https://search.proquest.com/docview/67923518
Volume 1740
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