The genetic background modifies the effects of the obesity mutation, 'fatty', on apolipoprotein gene regulation in rat liver.
BACKGROUND
Obesity is associated with disorders of plasma lipid transport in many, but not in all obese subjects. The effects of obesity on the regulation of genes involved in plasma lipid transport may depend on specific mutations causing or contributing to obesity and/or on interactions of a specific obesity mutation with the genetic background. The 'fatty' (Glu269Pro) leptin receptor mutation causes severe obesity associated with hypertriglyceridaemia and altered hepatic apolipoprotein gene regulation in Zucker fatty rats.


OBJECTIVE
To determine whether the effects of the obesity mutation 'fatty' on apolipoprotein gene regulation in rat liver depend on the genetic background.


METHODS
We studied hepatic apolipoprotein (apo) A-IV, A-I, and C-III gene expression in obese rats carrying the 'fatty' mutation on the background of the Zucker or Wistar strain.


RESULTS
Basal apoA-IV gene expression was increased in fatty rats of both strains, whereas apoA-I and apoC-III gene expression differed between Wistar and Zucker fatty rats: apoA-I gene transcription was reduced to half and apoC-III mRNA was increased two-fold in Wistar fatty, but not in Zucker fatty rats vs lean controls. A fish oil diet suppressed apoA-IV, but not apoA-I gene transcription in Wistar fatty rats, whereas in Zucker fatty rats apoA-IV transcription was unaffected, but apoA-I transcription was suppressed.


CONCLUSIONS
Interactions of the 'fatty' leptin receptor mutation with the genetic background significantly affect the basal and diet-induced regulation of the apoA-IV, C-III and A-I genes in rat liver. The genetic background may therefore be a major determinant of the consequences of a specific obesity mutation for plasma lipid transport.
Schuller
E
E
Department of Pediatrics, University of Vienna, Austria.
Patel
N
N
Item
C
C
Greber-Platzer
S
S
Baran
H
H
Patsch
W
W
Strobl
W
W
D000818:Animals; D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011924:Rats, Zucker; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin
D001053:Apolipoproteins; D002352:Carrier Proteins; D004041:Dietary Fats; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin