Alterations of lipid metabolism in men with hypotestosteronemia.

Studied relationship in serum concentration of testosterone and lipids in 35 men with a positive coronarographic finding and 30 sterile men, in comparison with a control group. From lipid parameters we determined serum concentration of cholesterol, triacylglycerols and apolipoprotein B, and lipid distribution in lipoprotein fractions. Serum testosterone concentration was found decreased in both the group as against the controls. As to lipid parameters, cholesterol concentration was depressed in the high-density lipoprotein (HDL) fraction of both the clinical groups. As increased apolipoprotein B level was seen in men with the positive coronarographic finding. The results point to a negative effect of lowered testosterone concentrations on lipid metabolism.     

Alterations of lipid metabolism in mice injected with endotoxin.

Some alterations in lipid metabolism in mice were observed by the intraperitoneal injection of endotoxin from Salmonella typhimurium. The content of serum triglyceride increased markedly in poisoned mice 16-24 hr postintoxication. The level of free fatty acid (FFA) in the serum of endotoxin-administered mice decreased in inverse proportion to an increase in the injected dose of endotoxin. The electrophoretic analysis of the serum lipoprotein on cellulose acetate membrane showed that pre beta-lipoprotein increased markedly and that FFA fraction in the poisoned mice sera disappeared 18 hr postintoxication. The activity of hormone-sensitive lipase in adipose tissue was elevated appreciably 2 hr after injection, but decreased more significantly after 18 hr than that in fasted control mice. On the other hand, the activity of lipoprotein lipase decreased in the post-heparin serum and adipose tissue 3 hr postintoxication, and decreased significantly after 16 hr. There were no significant differences between changes in the formation of active glycerol (alpha-GP) and in the activity of alpha glycerophosphate dehydrogenase (alpha-GPDH) in the mice liver with or without administration of endotoxin, and after 16 hr levels of both hepatic alpha-GP content and alpha-GPDH activity in poisoned mice showed a tendency to be slightly lower than those in fasted control mice.     

Alterations in rat lipid metabolism following ecdysterone treatment

The influence of ecdysterone on the lipid metabolism in liver and adipose tissue from rat was investigated using 14C-acetate and 32P-orthophosphate as precursors. Ecdysterone produced an increase in 14C-acetate incorporation into triglycerides. A concomitant decrease in free fatty acids and diglycerides was observed. The effect of ecdysterone on triglyceride lipase activity was investigated and a significant decrease was found. Ecdysterone produced a significant increase in the specific activity of phosphatidylethanolamine and phosphatidylserine in liver. On the contrary, the specific activity of phosphatidylcholine was reduced. In adipose tissue, the most evident effect observed was the increase of specific activity of phosphatidylcholine. These results contribute to knowledge of the heterophylic action of ecdysterone.     

Alterations in L fibroblast lipid metabolism and morphology during choline deprivation.

The growth of L fibroblasts in suspension culture after transfer directly to choline-free medium without a rinse was reduced to zero after 72 h. Monolayer cultures similarly treated multiplied at control rates for 96 h; one rinse of the latter prior to incubation in choline-free medium reduced growth at 48 h to 75% of control cells. A decrease in the size of cells in these rinsed monolayer cultures was apparent within 12 h, and preceded any changes in cell lipid composition; further decreases in cell size were observed at 24 and 48 h. After 24 h in choline-free medium the percent phosphatidyl choline had decreased only slightly and even at 48 h remained at 72 % of the value of control cells. At this time, however, there was a 50% decrease in the total phospholipid (PL) content of the cells, and a coincident 5–10-fold increase in the amount of triglyceride. There was no adaptive increase in the other principal PL classes. Changes in the ultrastructure of mitochondria were observed as early as 24 h; after 48 h without choline there was a decrease in the relative mitochondrial volume to 50% of control values. Alterations in the adhesive properties of choline-deprived cells may be related to altered lipid content or composition of the cell surface.     

Alterations in magnetic characteristics produced by intracellular particles

Comparisons were made of the magnetic susceptibility in tissue containing intracellular particles with respect to control tissue. Twenty animals, Sprague Dawley rats, were utilized of which ten were injected with FeTPPS₄-acetate particles under one micron in size. Magnetic susceptibility measurements were performed on tumor tissue from the injected and control animals. Studies showed an average susceptibility ratio of 0.79 in the tumors of the control group while in the injected group there was a susceptibility ratio of 1.25 in the tumors of the injected group as compared to the liver tissue in the injected group (p<0.001).     

Alterations in ether lipid metabolism and the consequences for the mouse lipidome

Alkylglycerol monooxygenase (AGMO) and plasmanylethanolamine desaturase (PEDS1) are enzymes involved in ether lipid metabolism. While AGMO degrades plasmanyl lipids by oxidative cleavage of the ether bond, PEDS1 exclusively synthesizes a specific subclass of ether lipids, the plasmalogens, by introducing a vinyl ether double bond into plasmanylethanolamine phospholipids. Ether lipids are characterized by an ether linkage at the sn-1 position of the glycerol backbone and they are found in membranes of different cell types. Decreased plasmalogen levels have been associated with neurological diseases like Alzheimer's disease. Agmo-deficient mice do not present an obvious phenotype under unchallenged conditions. In contrast, Peds1 knockout mice display a growth phenotype. To investigate the molecular consequences of Agmo and Peds1 deficiency on the mouse lipidome, five tissues from each mouse model were isolated and subjected to high resolution mass spectrometry allowing the characterization of up to 2013 lipid species from 42 lipid subclasses. Agmo knockout mice moderately accumulated plasmanyl and plasmenyl lipid species. Peds1-deficient mice manifested striking changes characterized by a strong reduction of plasmenyl lipids and a concomitant massive accumulation of plasmanyl lipids resulting in increased total ether lipid levels in the analyzed tissues except for the class of phosphatidylethanolamines where total levels remained remarkably constant also in Peds1 knockout mice. The rate-limiting enzyme in ether lipid metabolism, FAR1, was not upregulated in Peds1-deficient mice, indicating that the selective loss of plasmalogens is not sufficient to activate the feedback mechanism observed in total ether lipid deficiency.     

Alterations in regional brain neurotensin concentrations produced by atypical antipsychotic drugs.

Classical antipsychotic drugs, such as haloperidol, have been shown to increase the concentrations of neurotensin (NT) selectively in the nucleus accumbens and caudate nucleus of the rat. Several novel, putative antipsychotic drugs have also been found to produce increases in NT content in one or both of these brain regions. The present study sought to compare the effects of chronic treatment with three clinically efficacious atypical antipsychotic drugs, sulpiride, rimcazole and remoxipride, on regional brain NT concentrations to those of haloperidol. The concentrations of NT in five discrete brain regions were determined by a sensitive and specific radioimmunoassay. As previously reported, haloperidol increased NT concentrations in both the nucleus accumbens and caudate nucleus. Sulpiride and rimcazole produced significant increases in the concentration of NT in the caudate. NT concentrations were unaltered in any brain region by remoxipride at either of the doses tested. These data provide additional evidence for specific increases in regional brain NT concentrations produced by antipsychotic drugs.     

Alterations in brain lipid composition caused by vanadate

In an attempt to investigate the effect of sodium meta vanadate on membrane lipids in rat brain, in vivo and in vitro experiments were carried out. Intraperitoneal administration of vanadate (10 and 16 mumole/100 g) caused increase in cholesterol levels, whereas phospholipid levels were much less modified. These alterations brought about a significant increase in the ratio cholesterol/phospholipid. Concomitantly, an increase of both linoleic and docosahexanoic acids was observed, whereas arachidonic acid level was diminished. In all in vivo experiments the most effective dose on the parameters studied was 16 mumole/100 g. On the other hand, when vanadate (10(-3)-10(-5)M) was added in in vitro experiments a similar pattern of variation was obtained in cholesterol and phospholipid levels; however the variations were much less evident, 10(-3)M being the most effective dose. Likewise in the in vivo experiments, vanadate seems to act by increasing the levels of linoleic and docosahexanoic acids and by decreasing the arachidonic acid level. In contrast, the docosahexanoic acid level remained unchanged in in vitro experiments. These results suggest that both the brain delta 6 desaturase and extracerebral docosahexanoic acid synthesis are modified by vanadate. In conclusion, the present study indicates that vanadate is able to modify the cerebral lipid metabolism by altering the ratio cholesterol/phospholipid which in turn could lead to alterations in the membrane fluidity.     

In vitro lipid metabolism in the rat pancreas. I. Basal lipid metabolism.

1. The in vitro basal lipid metabolism of rat pancreatic fragments was compared with that in adipose tissue fragments and liver slices. 2. [1-14C]Acetate added to the media was mostly incorporated into palmitic acid and to a lesser extent into oleic acid. In addition, pancreatic tissue exhibited a marked capacity for elongation of polyunsaturated fatty acids by [1-14C]acetate and resulting desaturation when compared to adipose tissue and liver. 3. Data obtained in the presence of [U-14C]glucose, [1-14C]palmitate and 3H20 indicate that acetyl-CoA derived from glucose and from beta-oxidation of fatty acids contributed to de novo lipogenesis. 4. Oxidation of [1-14C]palmitic acid was 9-13 times higher in the pancreas than in adipose tissue or liver when expressed on a wet weight basis. 5. The fatty acid moiety of pancreatic glycerolipids could be derived from de novo synthesis, fatty acids added to the medium, or from fatty acids formed from the hydrolysis of endogenous lipids. The glycerol moiety could be derived either from glucose, or directly from glycerol through participation of glycerol kinase.     

Alterations in lipid and calcium metabolism associated with seizure activity in the postischemic brain

Transient ischemia is known to lead to a long-lasting depression of cerebral metabolic rate and blood flow and to an attenuated metabolic and circulatory response to physiological stimuli. However, the corresponding responses to induced seizures are retained, demonstrating preserved metabolic and circulatory capacity. The objective of the present study was to explore how a preceding period of ischemia (15 min) alters the release of free fatty acids (FFAs) and diacylglycerides (DAGs), the formation of cyclic nucleotides, and the influx/efflux of Ca(2+), following intense neuronal stimulation. For that purpose, seizure activity was induced with bicuculline for 30 s or 5 min at 6 h after the ischemia. Extracellular Ca(2+) concentration (Ca(2+)(e)) was recorded, and the tissue was frozen in situ for measurements of levels of FFAs, DAGs, and cyclic nucleotides. Six hours after ischemia, the FFA concentrations were normalized, but there was a lowering of the content of 20:4 in the DAG fraction. Cyclic AMP levels returned to normal values, but cyclic GMP content was reduced. Seizures induced in postischemic animals showed similar changes in Ca(2+)(e), as well as in levels of FFAs, DAGs, and cyclic nucleotides, as did seizures induced in nonischemic control animals, with the exception of an attenuated rise in 20:4 content in the DAG fraction. We conclude that, at least in the neocortex, seizure-induced phospholipid hydrolysis and cyclic cAMP/cyclic GMP formation are not altered by a preceding period of ischemia, nor is there a change in the influx/efflux of Ca(2+) during seizure discharge or in associated spreading depression.     

Hepatic lipid metabolism. Age-related changes in triglyceride metabolism.

Age-related changes in hepatic triglyceride formation have been described in developing rats. Triglyceride formation was measured in vitro in the presence of [14C]glycerol-3-phosphate, palmitate, ATP, CoA, and Mg2+ by using liver homogenates and microsomal fractions derived from various age groups of animals. Triglyceride formation was most active in one-day-old rats and then decrease with age. The increase in triglyceride formation following birth was prevented by the administration of puromycin or by denying suckling. In addition, changes in plasma and hepatic triglyceride concentrations, were also determined as functions of age. These studies suggest that the age of the animal significantly influences triglyceride metabolism.     

Alterations in canine coronary arteries produced by chronic cigarette smoking

Segments of left circumflex coronary artery were obtained from beagles that had been exposed to cigarette smoke for 2 years and from nonsmoking controls. A ring sample from each was used to determine passive (0-Ca2+ and 2 mM EGTA) and active (75 mM K+) force-length relations. Other contiguous samples were used to determine collagen and elastin content, water content and distribution, and total electrolyte content. No significant differences were found in passive mechanical properties or the collagen and elastin content of arteries from the two groups of animals. Maximum values of active force development were found to be increased in arteries from smoking dogs as were values on the ascending part of the active force-length curve. Total water content and the distribution space of an extracellular marker (60Co-EDTA) were not significantly different among arteries from the two groups. This along with the similarity of total electrolyte contents suggests that values of cell volume were not different between the two groups and that the above differences in active force development represent alterations in smooth muscle cells at the subcellular level. These results suggest that the contribution of chronic smoking as one of a group of cardiac risk factors may be due to an effect of augmenting coronary artery smooth muscle contractility.     

Alterations of energy metabolism induced by hexadecane in mice

Two groups of young male OF-1 mice were fed for 60 days with cafeteria or, as controls, with standard pellet diet respectively. At that time, both groups were daily treated with hexadecane (HDK) on the skin. HDK induced a drastic body weight loss much higher in cafeteria than control mice. White adipose tissue were exhausted after 4 days of treatment in controls but not after 10 days in cafeteria ones. HDK resulted in mobilization of liver glycogen in both groups while muscle glycogen decreased slightly in the end. Hexadecane treatment did not result in massively enhanced nitrogen metabolism, as the actual oxidation of amino acids decreased considerably as indicated by the low levels of plasma urea. The results could be explained by powerful and lasting effects of hexadecane on thermogenesis and metabolic reserve balance. The use of this material for pharmacological manipulation of body weight appeared difficult.