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Cholesterol feeding prevents adiposity in the obese female aromatase knockout (ArKO) mouse.
[aromatase deficiency]
The
aromatase
(
ArKO
)
knockout
mouse
develops
obesity
marked
by
increased
gonadal
fat
depots
.
This
obesity
is
characterized
by
pronounced
hypertrophy
and
hyperplasia
in
adipocytes
with
corresponding
increases
in
transcripts
involved
in
fat
development
.
Aromatase
deficiency
in
mice
and
humans
with
natural
mutations
of
the
aromatase
gene
also
leads
to
metabolic
syndrome
,
particularly
hepatic
steatosis
.
In
ArKO
mice
,
this
hepatic
steatosis
,
the
increased
body
weight
and
serum
triglycerides
are
surprisingly
prevented
by
cholesterol
feeding
.
We
sought
to
investigate
whether
the
reduction
in
body
weight
upon
cholesterol
feeding
is
reflected
in
gonadal
fat
depots
,
which
account
for
a
large
percentage
of
body
weight
in
the
ArKO
mouse
.
Indeed
,
gonadal
fat
depots
in
female
ArKO
mice
were
significantly
reduced
after
cholesterol
feeding
.
Concomitantly
,
adipocyte
hyperplasia
and
hypertrophy
were
dramatically
reduced
upon
cholesterol
feeding
in
ArKO
mice
.
Real-time
PCR
analysis
revealed
concurrent
changes
with
adipocyte
volume
in
the
levels
of
lipoprotein
lipase
,
caveolin-
1
and
CD
59
transcripts
.
Little
change
was
observed
in
levels
of
transcripts
involved
in
de
novo
fatty
acid
synthesis
,
beta
-oxidation
,
lipolysis
,
differentiation
and
cholesterol
metabolism
,
suggesting
that
cholesterol
feeding
prevents
hyperplasia
and
hypertrophy
of
ArKO
adipocytes
,
possibly
as
a
consequence
of
changes
in
transcript
levels
of
lipoprotein
lipase
and
therefore
fatty
acid
uptake
.
Diseases
Validation
Diseases presenting
"deficiency in mice"
symptom
aromatase deficiency
zellweger syndrome
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