Adipose
Tissue Metabolism: An Overview
Author:
Dr. Daniel Oscar Belluscio 1992-2007. ©All rights reserved
Introduction
Before earlier ‘50s it was generally believed that adipose tissue
was a simple repository of fat. The first report suggesting fat was
an active metabolic tissue was published by Von Gierke (493),
who noted that glycogen accumulation in adipose tissue took place if
an animal had been fasted and re-fed or else overfed from the start.
He concluded that the adipose tissue had its own internal metabolism.
However it was not until 1965 that an acceptable review on the subject
was published, comprising 894 pages, 69 chapters and about 4.100 references
on adipose tissue metabolism.
Now it is widely recognized that the main function of the fat cells
is to act as a reservoir of energy, as triglycerides, but it has also
been implicated in sex hormones metabolism (473).
The fat cell is one of the most metabolic- active tissues all over the
human body, nearly triplicating the blood circulation of any other organ
(155-264-414).
Adipocytes from living species are specially adapted for the uptake
and release of energy in the form of fatty acids. Fatty acids accumulate
in the form of triglycerides inside the fat cell, and released as fatty
acids back to the circulation as needed (13-298-393-467).
Depending on its localization, adipocytes show different metabolic turnovers
(307)
The mature fat cell contains a large lipid vacuole, which stretches
the cytoplasm and displaces the cell nucleus to the periphery of the
cell, showing the classic "signet-ring" appearance.
For these metabolic purposes the fat cells have two poles: a lipogenic,
where fatty acids are taken up form the circulation, and a lipolytic,
where triglycerides accumulated in the fat cell are released back into
the circulation (119).
Both poles are, in turn, subjected to different metabolic regulation,
which we will briefly discuss.
The Lipogenic Pole
Fatty acids for triglycerides synthesis are derived from hydrolysis
of circulating lipoproteins by LPL (lipoprotein Lipase), an enzyme that
hydrolyzes chylomichrons and very Low Density Lipoproteins to fatty
acids (197-221-222-348-384-413)
Since potentiality for blood fatty acids synthesis from capillaries
is minimal, the former represents the most important metabolic pathway
for triglycerides synthesis and later deposition into the fat cell.
The activity of LPL (and consequently the apposition of fat into the
fat cell) exhibits different activity levels depending on:
1. Nutritional status: It decreases during fasting or diabetes, and
rises in the fed state (261-374)
2. Fat topography and sex: During fertile life women tend to accumulate
fat (LPL High) preferentially in the femoral region compared to the
abdominal, which is difficult to mobilize (59-375-376-377-378-465).
3. During pregnancy the above mentioned findings are even more pronounced
than while lactancy. In the latter condition, triglycerides are no longer
taken up preferentially in the femoral region.
4. Age: LPL Activity decreases in women’s femoral region during
menopause. The same phenomena can be observed in male’s abdominal
region after their sixties.
The Lipolytic Pole
The lipolytic pole of the fat cell has been more researched, and obviously
is more understood than the lipogenic one (212-215-439)
A complex system of hormones and enzymes controls fatty acids release
from adipocytes: insulin, adrenergic receptors, thyroid hormones, adrenal
steroids. Phosphodiesterase activity, Proteinkinase, Hormone sensitive
Lipase (HSL) (440)
Activation of the adenylate cyclase by different substances generates
cyclic AMP, which provokes a cascade of protein phosphorilations, the
final step being the phosphorylation and activation of the Hormone sensitive
Lipase, which proceeds in turn to the enzymatic attack of stored triglycerides.
(151-253-350).
An interesting, and beneficial aspect from the therapeutic viewpoint,
is the finding that human adipose tissue possesses both Alfa and beta-cell
membrane adrenoreceptors. Binding of agonist to the beta receptor enhances
lypolisis, where an agonist that bind to alfa2 receptors inhibits lypolisis.
(16-17-18-19-20-21-22-23- 88- 148- 149- 153- 284-
292 - 303-394-498-499-500).
Lipolytic response to epinephrine (both beta 1 and alpha 2 adrenoreceptors)
is more marked in abdominal than in gluteal or femoral tissues. Moreover,
it has been suggested that the male pattern of body fat distribution
(fat mainly located in the abdominal region), may reflect greater alpha2
activity in the abdominal tissue of men.
Recent reports have demonstrated the possibility to locally modulate
those adrenoreceptors, to improve Body Contour deformities.
When compared obese patients managed with a Standard Hypocaloric Diet
submitted (or not) to adrenergic agents (lipolytic), regions treated
with Adrenergic drugs showed greater circumference reduction in treated
areas, as related to control sites.
It may be possible that these Investigations bear some relevance to
the treatment of Obesity.
This approach could hit both targets at the same time: rapid weight
loss and a pleasant body contour remodeling after treatment.