Accumulation of lipids

Yellow phosphorus was the first identified liver toxin. It causes accumulation of lipids in the liver. Several liver toxins such as chloroform, carbon tetrachloride, and bromobenzene have since been identified. I he forms of acute liver toxicity are accumulation of lipids in the liver, hepartxiellular necrosis, iii-trahepatic cholestasis, and a disease state that resembles viral hepatitis. The types of chrome hepatotoxicity are cirrhosis and liver cancer. 

Accumulation of lipids in the liver (steatosis) is one possible mechanism for liver toxicity. Several compounds causing necrosis of hepatocytes also cause steatosis. There are, however, some doubts that steatosis would be the primary cause of liver injury. Several compounds cause steatosis (e.g., puro-mycin, cycloheximide) without causing liver injury. Most of the accumulated lipids are triglycerides. In steatosis, the balance between the synthesis and excretion of these lipids has been disturbed (see Table 5.13). 

For a variety of reasons, lipid—mainly as triacylglycerol—can accumulate in the hver (Figure 25—6). Extensive accumulation is regarded as a pathologic condition. When accumulation of lipid in the Ever becomes chronic, fibrotic changes occur in the cells that progress to cirrhosis and impaired liver function. 

KIMURA Y, NAGATA Y, BRYANT c w, BUDDiNGTON R K (2002) Nondigestible oHgosaccharides do not increase accumulation of lipid soluble environmental contaminants by mice. J Nutr. 132 80-87. 

Babizhayev, M.A. (1989b). Accumulation of lipid peroxidation products in human cataracts. Acta Ophthalmol. 67, 281-287. 

Chelators of transition metals like iron can remove free iron from the injury cascade. The iron chelator, desferri-oxamine, prevented the accumulation of lipid peroxides in 15 min cardiac arrest model in dogs followed by 2 h of resuscitation (Komara et al., 1986). 

Atherosclerosis (AS) is a progressive disease characterized by the accumulation of lipids and the development of fibrosis in arterial walls. It is the pathophysiologic process behind cardiovascular disease whose clinical... 

Accumulation of lipid microspheres at the site of vascular lesions can be evaluated by three methods. First, electron microscopy can be used to examine the site of tissue damage. The second method is to follow the delivery of lipid... 

Of the various pharmacological actions of PGEj and PGI2, one action which has not yet been studied intensively, but seems to be important for the treatment of arteriosclerotic diseases, is their effect on vascularization. This suggests the need to determine if lipid microspheres accumulate at the site of vascularization. We are now conducting a study to investigate this possibility. Since the space between endothelial cells in new blood vessels is as big as that of vessels with sclerosis or inflammation, lipid microspheres are very likely to accumulate in new blood vessels. Figure 4 shows a schema of the distribution and accumulation of lipid microspheres at the site of vascular lesions. 

Glutaric aciduria type II, which is a defect of P-oxida-tion, may affect muscle exclusively or in conjunction with other tissues. Glutaric aciduria type II, also termed multiple acyl-CoA dehydrogenase deficiency (Fig. 42-2), usually causes respiratory distress, hypoglycemia, hyperammonemia, systemic carnitine deficiency, nonketotic metabolic acidosis in the neonatal period and death within the first week. A few patients with onset in childhood or adult life showed lipid-storage myopathy, with weakness or premature fatigue [4]. Short-chain acyl-CoA deficiency (Fig. 42-2) was described in one woman with proximal limb weakness and exercise intolerance. Muscle biopsy showed marked accumulation of lipid droplets. Although... 

Accumulation of lipids in spleen cells from a patient with Niemann-Pick disease. 

The main resistance to drug permeation is caused by the variant patterns of differentiation exhibited by the keratinized and nonkeratinized epithelia. As mucosal cells leave the basal layer, they differentiate and become flattened. Accumulation of lipids and proteins also occurs. This further culminates in a portion of the lipid that concentrates into small organelles called membrane-coating granules (MCGs). 

Figure 32 Accumulation of lipids and proteins with age in the large form of horse-mackerel showing overall trends (smooth curves) and annual cycles. (After Shulman, 1972a.) Solid lines proteins, broken lines lipids. Note the greater annual fluctuations of lipids.

Post-spawning (pre-wintering feeding). This period is marked by intensive lipid accumulation that will allow normal living of the population later, when food consumption has ceased or been much curtailed. Fish accumulate substantial reserves of triacyl-glycerols, and the content of creatine phosphate in the muscle and glycogen in the muscle and liver increase. A similar increase is found in the content of serum proteins, albumin in particular, which provides for future gonad development. The increase in protein continues, but is less than the accumulation of lipids. 

Up to now, different aspects of substance and energy utilization for total production have been examined. It is necessary to look at somatic and generative production, protein retention and accumulation of lipid and, finally, the efficiency of utilization of assimilated food. The total K is the sum of somatic production K and generative production K. ... 

Thus the correlation between the food assimilated for production of protein and accumulation of lipid can be numerically represented as the ratio between the two processes. 

Table 19 demonstrates the results of the calculation, using data from Table 11. It can be seen that, depending on the species, from 2% to 24% of the dry food substance is assimilated for the total protein production and 0.7% to 8.0% for the total lipid production. Assuming that protein and lipid are adequately used for the somatic and generative productions, one can make relevant estimates (Table 19). The resulting data of K2 of P of protein and lipid are of especial interest. They indicate the efficient assimilation of nutrients to provide somatic production and accumulation of lipid. The following ratios between food assimilated for protein and lipid production have been obtained for Black Sea fish 2.6 1 in anchovy, 2 1 in sprat, 2.1 1 in horse-mackerel and red mullet, 2.7 1 in pickerel, and 4 1 in whiting.

Table 19 Efficiency of the utilization of assimilated dry matter for the production of protein and the accumulation of lipid (%).

It should always be borne in mind that published figures for the ecological efficiency of food assimilated for production are averages from studies made over many years. The picture may be very different in years of shortage or plenty, when efficiency, especially as estimated in the period of growth and accumulation of lipid, differs a great deal from the average. 

Lipid accumulation differs from somatic growth, since food plankton increases in abundance from the Mediterranean, via the Black to the Azov Sea, a situation that promotes the greatest accumulation of lipids in Azov fish. 

In the Black Sea, the production of protein and accumulation of lipid occur simultaneously in cold-water fish, while in the warm-water fish the activities are separated. Pickerel, which are intermediate as regards temperature preference, display similarities to both other forms. Like the warm-water fish, the major part of production occurs during the warm season, although the amplitude of the biological rhythms is not as pronounced. Like the cold-water whiting, the pickerel use protein, not lipid, as a main reserve. 

Concepts of metabolic processes may be distorted if they are based solely on energy. We have already shown that protein production and the accumulation of lipids differ between the three races of European anchovy, but the energy equivalents of the body weights alter identically in all three (Shulman and Urdenko, 1989), even though the metabolic patterns differ. No fish farmer will consider only the caloric content of the feed, but will concentrate on a proper balance of constituents. Only considerations of both matter and energy will give a true understanding of all the processes involved. 

Lipids are toxicologically important for several reasons. Some toxic substances interfere with lipid metabolism, leading to detrimental accumulation of lipids. Many toxic organic compounds are poorly soluble in water, but are lipid soluble, so that bodies of lipids in organisms serve to dissolve and store toxicants. 

Another genetic metabolic disorder is Fabry disease, which is related to a deficiency in the enzyme a-galactosidase A. This enzyme is involved in the metabolism of lipids, and its deficiency leads to the accumulation of lipids in the eyes, kidneys, and nervous and cardiovascular systems. In 2001, the biopharmaceutical called Fabrazyme was approved, which consists of recombinant a-galactosidase A and is produced by genetically modified CHO cells. 

---