TY - JOUR
T1 - Conjugated linoleic acid activates peroxisome proliferator-activated receptor α and β subtypes but does not induce hepatic peroxisome proliferation in Sprague-Dawley rats
AU - Moya-Camarena, Silvia Y.
AU - Vanden Heuvel, John P.
AU - Belury, Martha A.
N1 - Funding Information:
The authors thank Dr. J. Tugwood (Zeneca Central Toxicology Laboratory, UK) for providing pSG5-mPPARβ and psV-GL2-PPRE-luciferase reporter plasmid and Dr. S.A. Kliewer for mPPARβ-GAL4 and (UAS) 5 -CAT plasmids. D. Van Horn and K. Nickel are thanked for electron microscopy work and peroxisome proliferation analysis. We also thank K.L. Liu, C. Kavanaugh, A. Kempa-Steczko and M. Lu for their excellent technical assistance. This work was supported by AICR Grant no. 96B071. S.Y.M.-C. was supported by AICR and CONACyT (Mexico).
PY - 1999/1/4
Y1 - 1999/1/4
N2 - Since conjugated linoleic acid (CLA) has structural and physiological characteristics similar to peroxisome proliferators, we hypothesized that CLA would activate peroxisome proliferator-activated receptor (PPAR). We compared the effects of dietary CLA (0.0, 0.5, 1.0 and 1.5% by weight) with a peroxisome proliferator (0.01% Wy-14,643) in female and male Sprague-Dawley (SD) rats. Dietary CLA had little effect on body weight, liver weight, and hepatic peroxisome proliferation, compared to male rats fed Wy-14,643 diet. Lipid content in livers from rats fed 1.5% CLA and Wy-14,643 diets was increased (P < 0.01) when compared to rats fed control diets regardless of gender. Hepatic acyl-CoA oxidase (ACO) mRNA levels were increased 3-fold in male rats fed 1.5% CLA diet compared to rats fed control diets while Wy- 14,643 supported ~30-fold ACO mRNA accumulation. A similar response was observed for liver fatty acid-binding protein (L-FABP) mRNA. The effect of dietary treatments on hepatic PPAR-responsive genes in female rats was weaker than in male rats. The (9Z, 11E)-CLA isomer activated PPARα in transfected cells to a similar extent as Wy-14,643, whereas the furan-CLA metabolite was comparable to bezafibrate on activating PPARβ. These data suggest that while CLA was able to activate PPARs it is not a peroxisome proliferator in SD rats.
AB - Since conjugated linoleic acid (CLA) has structural and physiological characteristics similar to peroxisome proliferators, we hypothesized that CLA would activate peroxisome proliferator-activated receptor (PPAR). We compared the effects of dietary CLA (0.0, 0.5, 1.0 and 1.5% by weight) with a peroxisome proliferator (0.01% Wy-14,643) in female and male Sprague-Dawley (SD) rats. Dietary CLA had little effect on body weight, liver weight, and hepatic peroxisome proliferation, compared to male rats fed Wy-14,643 diet. Lipid content in livers from rats fed 1.5% CLA and Wy-14,643 diets was increased (P < 0.01) when compared to rats fed control diets regardless of gender. Hepatic acyl-CoA oxidase (ACO) mRNA levels were increased 3-fold in male rats fed 1.5% CLA diet compared to rats fed control diets while Wy- 14,643 supported ~30-fold ACO mRNA accumulation. A similar response was observed for liver fatty acid-binding protein (L-FABP) mRNA. The effect of dietary treatments on hepatic PPAR-responsive genes in female rats was weaker than in male rats. The (9Z, 11E)-CLA isomer activated PPARα in transfected cells to a similar extent as Wy-14,643, whereas the furan-CLA metabolite was comparable to bezafibrate on activating PPARβ. These data suggest that while CLA was able to activate PPARs it is not a peroxisome proliferator in SD rats.
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U2 - 10.1016/S0005-2760(98)00121-0
DO - 10.1016/S0005-2760(98)00121-0
M3 - Article
C2 - 9989264
AN - SCOPUS:0033521702
SN - 1388-1981
VL - 1436
SP - 331
EP - 342
JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
IS - 3
ER -