Foto del docente

Massimo Cocchi

Adjunct professor

Department of Veterinary Medical Sciences

Research

BIOCHEMISTRY OF NUTRITION AND LIPID METABOLISM

1) Ethanol and lipid

2) Studies concerning unusual fatty acids

3) Dietary lipids and tissue lipids

4) Studies about Essential Fatty Acids (EFA)

5) Fatty Acids of the n—6 and n-3 series

6) Cellular nutrition

7) Lipid metabolism during development and growth

8) Platelet fatty Acids in Major Depression and Ischemic Heart Disease



1) Ethanol and lipid metabolism

The effect of ethanol on lipid homeostasis has been studied in rat liver. The phospholipid pattern and the correlated fatty acid modifications were in dose relation to the entity of ethanol intake. At an early stage, this phenomenon was reversibie, as ethanol was excluded from the diet, but if at the same time animals received an hypoproteic diet, which worstened the biochemical damage, it could not return to a normal status. The influence of ethanol Cn cuitured cells has been studied by evaiàating the celi growth and respiration in the presence of different ethanol concentrations.

2) Studies concerning unusual fatty acids

Studies performed both in experimental animals and in men confirmed perplexity concerning the use of oils containing a large percentage of erucic acid (C 22:1 n-9), which is responsible for some biochemical, functional and anatomic changes in the heart, where large intake of this acid might induce histiocitary infiltration.
These investigations had shown the presence of C 22:1 n—9 in rat heart, both <in  toto> and in phospholipidic fractìon. Studies perforrned on serum had pointed out that the dietary intake of colza and rapeseed—oils)ifluenced the acidic composition of the plasma lipids, changing their normal pattern also in man.
The results obtained with these experimental studies have been submitted to the Ministerial Committee, to determine the utilization rules for the use af the above mentioned oils. Moreover, the influence of trans fatty acid intake on the acidic composition of different organs (adipose tissue, heart, liver ecc.) has been studied. The increased consumption of dietary hydrogenated fats, containing these non—physiological isomers, has motivated these studies. The results have notably evidenced a trans fatty acid accumulation in the considered organs, even though in different percentages, not proportional to the dietary intake of these isomers. The administration of a large amount of trans fatty acids also affected essential fatty acid and cholosterol level) in the plasma. Regarding the influence of these stereoisomers on the respiratory activity of heart mitochondria, it has been noted that, in particular stress conditions, mitochondrial activity was decreased, probably in relation to the presence of trans fatty acids in the heart phospholipids.

3) Dietary lipids and tissue lipids

Research about dietetic and tissue lipids correlations have been performed on rats for different times (60, .120, 180 and 360 days) until the maximum of 540 days, in order to evaluate the effects of long term treatmentIt has been pointed out that not only stored lipids were influenced by dietary modifications, but also cellular lipids may be affected later on. Even brain lipids, generally considered as constant, changed in function of the different dietary fatty acids. This concerned not only the gliceride but also the phospholipid fraction. The same modifications were observed in heart, liver, muscle and blood. Significant modifications in total lipids, phospholipids and in fatty acid composition were observed in mitochondria, in microsomes and, to a less extent, in the hepatocita nucleus. In order to elucidate the quantitative lipid and coenzyme Q10 modifications, certain diets, such as alipidic (Dewel), hypercholesterolemic (Peifer) and vitamine E deficient (Edwin) were used. All these diets caused a notable decrease of coenzyzne Q10, especially in the heart. The lipid content and the fatty acid pattern have been also studied in Rinolophus ferrum aequinum during hibernation. Results showed a decrease in total lipid content, with detectable percent modifications in the fatty acid composition. In particular, essential fatty acids (EFA) and oleic acid decreased while saturated fatty acids increased and no modifications were observed in the brain.


The long chain fatty acid metabolism in ruminant

Some studies performed on sheep have shown that the fatty acids present in rumen are different from those present in the diet, and that dietary linoleic and linolenic acid hydrogenation and new odd ramificated fatty acid biosynthesis are operating.
The «in vitro» calculation of long chain fatty acid biosynthesis in the ovine rumen was possible using an alipidic diet. It showed not only the presence of odd ramificated fatty acid, but also linoleic acid biosynthesis.

5) Fatty acids of the n—6 and n—3 series

The most recent knowledge about polynsaturated fatty acids was concerned with the problem correlated to n—6 and n-3 fatty acids. These acids are very important not only for their role in cellular and sub cellular structure composition, but also as precursors of prostanoids, which have important and differentiated physiological functions. In particular, gamma—linolenic acid (n-6) is very effective in modulating the balance between aggregating and non aggregating prostaglandins, by supporting PGEI synthesis in spite of PGE2. The higher fatty acids of the gamma—linolenic family (n—3) have a fundamental structural function in brain, retina, gonads, etc. Research performed in this field has provided greater knowledge abaut n—6 and n—3 fatty acid metabolic turnover, the dose correlations among fatty acids of the two series, as well as their competition towards the specific elongation and desaturase enzymes. In particular, some differences in the organ acidic composition of rats fed with diets having different n-6 and n—3 fatty acid amounts have been reported. Such differences were noted also in mitochondria, but they had no influence on normal function, as the mitochondrial respiratory activity appeared to be normal. Dietary alfa—linolenic acid supply seems to be very important for the nervous system. Following alfa—linolenic intake, some structural modifications are detectable, both in the brain «in toto» and in single structures such as optic and trigeminal nerve. C 18:3 n—3 metabolism has been observed also in the chick embryo. It has been reported that the area of biosynthesis of specific fatty acids in the maturation stage shifts towards particular organs at the end of embryo growth period.

4) Studies about Essential Fatty Acid (EFA)

Some investigations have tried to determine the EFA requirements
The results obtained in experimental animals (rats) pointed out that the largest EFA requirement corresponded to the central period of life, being higher far men than for women. This has allowed toevaluate the EFA requirements on the basis of the tissue lipid homeostasis and of the total fatty acid pattern. Large intakes of EFA, at first, determined an increase af lipid fatty acid unsaturation in all tissues, including the brain, and in subcellular structures, like 1iver mitochondria. Afterwards, the phenomenon decreased and the biochemical aspect of these structures returned to normality. This seemed to show a tissutal defence mechanism against too high EFA amounts. The adipose tissue also had its own homeostatic control and didn't store up, in these experimental conditions, essential fatty acids beyond a definite limit. On the contrary, collateral research using EFA deficient diets has shown alterations of spontaneous and provoked motility in experimental animals and, moreover, a decrease in learning ability and in recent and remote memory.

6) Cellular nutrition

This research line has been performed on cultured heart ceils from chick embryo. The effects of different nutrients, like glucides, ethanol and phospholipids on   the proliferation and the respiratory activity of chick embryo myocardial cells, cultured in hanging drop, have been evaluated. The addition of phospholipids to the cultures, aL low concentrations, has shown a positive effect on cell growth, both in basal and in stress conditions while at higher concentrations, phospholipids appeared to be negative. These results differed in relation to the organ from which phospholipids were extracted, and this well correlated with some clinical studies based on enteral or parenteral phospholipid supply in men. Briefly, it has been shown that exogenous phospholipids, at adequate concentrations, can stimulate the rate ot macromolecular synthesis processes, by potentiatìng the action of serum growth factors in cultured cells. As far as the mechanism of action of phospholipids is concerned, this appears to be exerted through the modulation of some endogenous factors, such as cyclic nucleotides (AMPc e GMPc) and poliyamines (putrescine, spermidine, spermine), closely involved in the regulation of biochemicai processes notable linked to the rate of cell growth and division.

7) Changes in lipid metabolism during development and growth

The tissues of the developing chick embryo display particularly high levels of C20 and C22 polyunsaturated fatty a.sids. These fatty acids are derived during yolk lipid uptake by synthesis within the yolk sac membrane and preferential absorption of phosphatidyl ethanolamine. The yolk contains a finite level of vitamin E. The marked increase in double bonds associated with polyunsaturated fatty acid accumulation in the embryo tissues therefore poses the question whether adequate levels of vitamin E are maintained thrcughout yclk lipid absorption to afford protection against peroxidation. The relationship between vitamin E and polyunsaturated fatty acid levels in the yolk contents, yolk sac membrane and tissues during development of the chick embryo was studied.

8) Platelet Fatty Acids in Depressive Disorder and in Ischemic Heart Disease

In 2005 he started, with Lucio Tonello, to study the platelet fatty acids in groups of patients (Depressive and Ischemic) realizing a combination between Biochemistry and Artificial Neural Network which has allowed to identify the depressive and the ischemic population against the apparently normal people.

On the argument many papers, meetings and conferences have been hold.

 

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