Comparative effect of fenofibrate on hepatic desaturases in wild-type and peroxisome proliferator-activated receptor alpha-deficient mice.
In this study is presented the effect of fenofibrate, a prototypical peroxisome proliferator of the fibrate class, on wild-type and peroxisome proliferator-activated receptor alpha (PPARalpha)-/- mouse liver FA profile, desaturase mRNA levels, and activities. We established that, following peroxisome proliferator exposure, the hepatic FA profile was greatly modified. These modifications in hepatic FA content required the expression of PPARalpha, as they are suppressed in transgenic mice deficient in this nuclear receptor. Following peroxisome proliferator exposure, delta6- and delta5-desaturase mRNA levels and activities were increased in wild-type but not in PPARalpha-deficient mouse liver. These results suggest the involvement of PPARalpha in the control of hepatic delta6- and delta5-desaturases in mice. Their roles in minimizing long-chain PUFA depletion in the liver during peroxisome proliferator exposure are discussed.
Guillou
Hervé
H
Laboratoire de Biochimie ENSAR-INRA, 35042 Rennes, France.
Martin
Pascal
P
Jan
Sophie
S
D'Andrea
Sabine
S
Roulet
Alain
A
Catheline
Daniel
D
Rioux
Vincent
V
Pineau
Thierry
T
Legrand
Philippe
P
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000032:analysis; D011345:Fenofibrate / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
D005227:Fatty Acids; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D044943:Fatty Acid Desaturases; D011345:Fenofibrate