Genetic variation in the mouse model of Niemann Pick C1 affects female, as well as male, adiposity, and hepatic bile transporters but has indeterminate effects on caveolae.
We have previously shown that male Npc1 heterozygous mice (Npc1(+/-)), as compared to homozygous wild-type mice (Npc1(+/+)), both maintained on the "lean" BALB/cJ genetic background, become obese on a high fat but not on a low fat diet. We have now extended this result for female heterozygous mice. When fed high-fat diet, the Npc1(+/-) white adipose weight is also increased in females, therefore following the same trend as males. Bile transporters which had previously been found to be altered in Npc1(-/-) mice on a high fat diet, showed related, but small, changes in mRNA levels but large changes in protein expression. We have addressed the possible role of caveolae in these differences. It has long been known that caveolin 1 is increased in the liver (sex not specified) of Npc1(+/-) (compared to Npc1(+/+) and Npc1(-/-)) mice and in heterozygous cultured skin fibroblasts of NPC1 carriers. We now find that caveolin 1 is increased in male, but not female liver and female, but not male adipose tissue. The caveolin 1 increase was not accompanied by changes in another caveolar protein, polymerase1 and transcript release factor (Ptrf). The numbers of caveolae in female adipose cells could not be correlated with levels of caveolae. Thus, we conclude that Npc1 affects female as well as male obesity and bile transporters but that effects on caveolin 1 are not discernible.
Dept of Pediatrics, Box 5073, University of Arizona Health Sciences Center, Tucson, AZ 85724-5073, USA. dajelinek@salud.unm.edu
David A
DA
Jelinek
Bita
B
Maghsoodi
Ivan A
IA
Borbon
Rhiannon N
RN
Hardwick
Nathan J
NJ
Cherrington
Robert P
RP
Erickson
D052436:Adipose Tissue, White / Q000502:physiology; D050154:Adiposity / Q000235:genetics*; D000818:Animals; D001646:Bile / Q000378:metabolism*; D021941:Caveolae / Q000502:physiology*; D051242:Caveolin 1 / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D014644:Genetic Variation; D006579:Heterozygote; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D012727:Sex Characteristics
D051242:Caveolin 1; D047908:Intracellular Signaling Peptides and Proteins; D000077296:Niemann-Pick C1 Protein; C106831:Npc1 protein, mouse; D011506:Proteins