Background
In the past few years, much
progress has been made in the understanding
of how people maintain
body
weight and how energy homeostasis
is affected. Many homeostastic
processes including appetite and
food
intake are controlled by neuroendocrine
circuits involving the
C.N.S.
Mean while the C.N.S. may
directly
regulates adipocyte metabolism. Objective
In this work we aim to show and
prove that central ghrelin in physiological
not pharmacological dose
plays
an important role in maintenance
of energy homeostasis.
Methods
2 sets of experiments were
carried out to investigate both the
acute and chronic effects of intrace- rebroventricular Ghrelin on energy
homestasis and adipocyte metabolism.
Each set of experiment include
3
groups, each group consists of 8
rats
:
group A (control group) : Were injected
daily with saline in a dose of 5
ML
saline, group B (physiological
dose
group) Were injected daily with
ghrelin
in a dose of 2.5 nmol, group < br />C
(pharmacological dose group):
Were
injected daily with ghrelin in a
dose
of 4 nmole. For all groups,
samples
were collected both in the
fasting
and in the postprandial
states. In the acute study, the rats were
sacrificed after 24 hours and in the
chronic study, the rats were sacrificed
after 6 days. In all chronic
groups
beside the blood samples:
the
epididymal white adipose tissue
was
dissected for estimation of trigly- ceride content, weight measurement
and histological analysis, mRNA expression
of the lipoprotein lipase enzyme,
the carnitine palymitoyl transferase
enzyme, UCP2 and the UCP1
Results
Group B (physiological dose) in
the acute study: plasma glucose,
free fatty acids and triglycerides
showed significant increased as
compared with the control group < br />(group A) while in the postprandial it
showed significant decrease in all
these parameters as compared with
the control group and in the pharmacological
dose showed significant
increase
in fasting plasma glucose,
plasma
free fatty acids and insignificant
change in triglyceride level as
compared
with the control group.
However in the chronic study
the pharmacological doses showed
insignificant change in plasma glucose
while significant decrease in
plasma
free fatty acids and triglyceride
as compared with the control
group.
The physiological dose by
chronic
study showed significant increase
in plasma glucose and non
significant
change in plasma free fatty
acids and triglycerides as compared
with the control group. Also in the pharmacological group (gpC)
showed an increase in the body
weight an increase in epididymal
WAT tissue weight gain and triglyceride
concentration in WAT tissue,
Also
gpC showed significant increase
in mRNA level of lipoprotein
lipase
(increase by 200% of control),
significant
decrease in mRNA level
of
carnitine palmitoyl transferse ?
(decrease
by 60% of control), significant
decrease in mRNA level of
UCP1
(decrease by 60% of control)
and
significant increase in mRNA
level
of UCP2 (increase by 50% of
control). Conclusion
Central ghrelin in its physiological
concentration has a subtle effect
which enables it to maintain constant
fat stores. Central ghrelin in the
pharmacological dose enhances triglyceride
storage and decrease level
of
energy expenditure thus it causes
a
+ve energy balance and also it
may
worsen a diabetic state.