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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...
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Published in: | Gene 2012-01, Vol.491 (2), p.128-134 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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.
► Female
Npc1 heterozygotes, but not wild-type, mice become obese on a high fat diet. ► High fat diet up-regulated some bile acid transporters in female
Npc1 heterozygotes. ► Changes in caveolar proteins or numbers did not explain the
Npc1 obesity effects. |
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ISSN: | 0378-1119 1879-0038 |
DOI: | 10.1016/j.gene.2011.10.010 |