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Adipose tissue metabolism: An overview

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 tryglicerides, 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.

Fatty acids for tryglicerides 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 triglyceride 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.(Fat distribution).

4. Age: LPL Activity decreases in women’s femoral region during menopause. The same phenomena can be observed in males abdominal region after their sixties .

The lipolytic pole of the fat cell has been more researched, and obviously is more understood than the lipogenic one.(212-215-439) ( Figure 6)

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 lipolysis, where an agonist that bind to alfa2 receptors inhibits lipolysis.(16-17-18-19-20-21-22-23- 88- 148- 149- 153- 284- 292 - 303-394-498-499-500)

Lipolytic response to epinephrine (both betal 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 Hypochaloric 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.