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The implications of these changes for liver metabolism are disastrous only
3 weeks in such working protocol induced an increase in triglyceride accu-
mulation. These observation consonants with previous observations show-
ing that rats without SIRT1 develop liver steatosis while mice that
overexpress SIRT1 are protected against diet-induced liver steatosis.
29
The low levels of SIRT1 observed in rats eating in their inactive phase agree
with their propensity to accumulate abdominal fat and with their significant
overweight. Moreover, the decreased levels of
Pgc1a
that
we observed in our model agree with the studies showing that SIRT1 stim-
ulates the transcription of
Pgc1a
,
Ppara
,
and Pparg
suggest that the consequence of low
SIRT1
and
Pgc
-
1a
,
Ppara
,
and Pparg
together with the
decrease of the PPAR's in ARP rats may lead to overweight and metabolic
disturbances as observed, for example, in the
Sirt1
knockdown mice. More-
over in line with these observations, it has been shown that an increase of
of SIRT1 observed in the present study may reflect a state of lesser sensitivity
for insulin. Therefore, the surprising outcome of our recent research was
that, in spite of several studies that show that the nuclear receptor genes like
Ppara
illustrates that metabolic genes such as
Nampt
,
Sirt1
and
Ppara
and
Pparg
may not
always be linked with the core clock genes.
10. CONCLUSIONS
At present, the current literature suggests a tight coupling between
food and the expression of clock genes and metabolic genes in organs like
the liver. This review illustrates that indeed tight links exist between clock
genes and metabolic genes. However, when the animal as a whole, and not
organ tissues
in vitro
, is examined, many other network possibilities and ele-
ments play a role in determining how also at a cellular level the systems react
to changes in food availability conditions. This is especially evident under
so-called desynchronization conditions whereby food and activity are
imposed at times when the animal normally rests. Such
in vivo
conditions
show that when the network is in place and the SCN is able to influence
also the cellular events in the liver but when the network because of the con-
ditions is desynchronized, the coupling between clock genes and metabolic
genes is lost showing that
in vivo
other relationships may prevail than
in vitro
.
This suggests that these relationships between clock genes are not hardwired
but can be malleable by the conditions. It is interesting that especially food
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