PMID- 15362034
OWN - NLM
STAT- MEDLINE
DCOM- 20041019
LR  - 20190707
IS  - 0016-5085 (Print)
IS  - 0016-5085 (Linking)
VI  - 127
IP  - 3
DP  - 2004 Sep
TI  - Activation of PPAR gamma and delta by conjugated linoleic acid mediates 
      protection from experimental inflammatory bowel disease.
PG  - 777-91
AB  - BACKGROUND & AIMS: The molecular targets for the protective actions of conjugated 
      linoleic acid (CLA) on experimental inflammatory bowel disease (IBD) are unknown. 
      We used a loss-of-function approach to investigate whether CLA ameliorated 
      colitis through a peroxisome proliferator-activated receptor gamma (PPAR 
      gamma)-dependent mechanism. METHODS: The expression of PPAR gamma, delta, and 
      their target genes in the colon of mice fed control or CLA-supplemented diets was 
      assayed after a 7-day dextran sodium sulfate (DSS) challenge by quantitative 
      real-time polymerase chain reaction (PCR). Additionally, nuclear factor-kappa B 
      (NF-kappaB) p65 activation was quantified in the colon. To determine the 
      involvement of PPAR gamma in the mechanism of action of CLA directly, specific 
      deletions of PPAR gamma in the colon were performed in mice by using the Cre-lox 
      recombination system. Colonic PPAR gamma null mice and wild-type littermates were 
      fed either a CLA-supplemented or a control diet for 42 days and challenged with 
      2.5% DSS. The therapeutic efficacy of CLA also was examined by using the CD4 + 
      CD45RB hi transfer colitis model. RESULTS: CLA induced PPAR gamma and delta, 
      transcriptionally modulated PPAR gamma and delta-responsive gene clusters 
      involved in lipid metabolism (uncoupling protein [UCP]1, UCP3, PPAR gamma 
      coactivator 1alpha [PGC-1alpha], and CD36) and epithelial cell maturation (Gob-4 
      and Keratin 20). Additionally, CLA repressed tumor necrosis factor alpha 
      (TNF-alpha) expression and NF-kappaB activation while inducing the 
      immunoregulatory cytokine transforming growth factor beta 1 (TGF-beta 1 ). 
      Clinically, CLA ameliorated DSS- and CD4 + -induced colitis. Loss of the PPAR 
      gamma gene in the colon abrogated the beneficial effects of CLA in DSS colitis. 
      CONCLUSIONS: Our studies provide molecular evidence in vivo, suggesting that CLA 
      ameliorates colitis through a PPAR gamma-dependent mechanism.
FAU - Bassaganya-Riera, Josep
AU  - Bassaganya-Riera J
AD  - Laboratory of Nutritional Immunology & Molecular Nutrition, Department of Human 
      Nutrition, Foods and Exercise, Virginia Polytechnic Institute and State 
      University, Blacksburg, Virginia 24061, USA. jbassaga@vt.edu
FAU - Reynolds, Kathryn
AU  - Reynolds K
FAU - Martino-Catt, Susan
AU  - Martino-Catt S
FAU - Cui, Yongzhi
AU  - Cui Y
FAU - Hennighausen, Lothar
AU  - Hennighausen L
FAU - Gonzalez, Frank
AU  - Gonzalez F
FAU - Rohrer, Jurg
AU  - Rohrer J
FAU - Benninghoff, Alejandro Uribe
AU  - Benninghoff AU
FAU - Hontecillas, Raquel
AU  - Hontecillas R
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - 0 (Carrier Proteins)
RN  - 0 (Linoleic Acids, Conjugated)
RN  - 0 (NF-kappa B)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Rela protein, mouse)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Transcription Factors)
SB  - IM
CIN - Gastroenterology. 2004 Sep;127(3):994-6. PMID: 15362056
MH  - Animals
MH  - Carrier Proteins/immunology
MH  - Gene Expression Regulation/immunology
MH  - Inflammatory Bowel Diseases/diet therapy/*immunology
MH  - Linoleic Acids, Conjugated/genetics/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Models, Animal
MH  - NF-kappa B/immunology
MH  - Neoplasm Proteins/immunology
MH  - Receptors, Cytoplasmic and Nuclear/*biosynthesis/genetics/immunology
MH  - Transcription Factor RelA
MH  - Transcription Factors/*biosynthesis/genetics/immunology
EDAT- 2004/09/14 05:00
MHDA- 2004/10/20 09:00
CRDT- 2004/09/14 05:00
PHST- 2004/09/14 05:00 [pubmed]
PHST- 2004/10/20 09:00 [medline]
PHST- 2004/09/14 05:00 [entrez]
AID - S0016508504011813 [pii]
AID - 10.1053/j.gastro.2004.06.049 [doi]
PST - ppublish
SO  - Gastroenterology. 2004 Sep;127(3):777-91. doi: 10.1053/j.gastro.2004.06.049.