Fatty Acids In Mice Research Articles

Inhibition of the mitochondrial oxidation of fatty acids by tetracycline in mice and in man: possible role in microvesicular steatosis induced by this antibiotic.

Intravenous administration of high doses of tetracycline may produce severe microvesicular steatosis of the liver in man. A similar disease is observed after ingestion of drugs which inhibit hepatic mitochondrial fatty acid beta-oxidation and in subjects with various inborn defects in this metabolic pathway. We therefore determined the effects of tetracycline on the mitochondrial oxidation of fatty acids in mice and in man. In vitro, addition of tetracycline 0.25, 0.5, 1 or 2 mM inhibited by 15, 38, 56 and 65%, respectively, the formation of beta-oxidation products during incubation of palmitic acid with mouse liver mitochondria and the various cofactors necessary for beta-oxidation. Inhibition was reversible. Inhibition appeared even greater with human liver mitochondria. Tricarboxylic acid cycle activity, assessed by the in vitro formation of [14C]CO2 from [1-14C]acetylcoenzyme A by mouse liver mitochondria, was inhibited by 25, 32 and 43%, respectively, in the presence of 0.5, 1 or 2 mM of tetracycline. In vivo, administration of tetracycline, 0.25 or 1 mmole per kg, inhibited by 53 and 84%, respectively, the exhalation of [14C]CO2 during the first 3 hours following the administration of a tracer dose of [U-14C]palmitic acid. Administration of tetracycline, 0.0625, 0.25 or 1 mmole per kg, 6 hr before the measurement, increased hepatic triglycerides by 100, 170 and 250%, respectively. After 1 mmole per kg, accumulation of hepatic triglycerides was maximum at 24 hr, reaching 9-fold the control value; liver histology showed microvesicular steatosis at 6 and 24 hr. We conclude that tetracycline inhibits the mitochondrial oxidation of fatty acids in mice and in man.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of pancreatic digestive enzyme secretion induced by volatile fatty acids in mice, Japanese field voles and goats

1. 1. The secretory response of the exocrine pancreas to volatile fatty acids was investigated in the isolated preparations of mice, Japanese field voles and goats. 2. 2. The amylase content in pancreases of the voles was half that of the mice, and the trypsin content was four times higher than that of the mice. 3. 3. Amylase release to volatile fatty acids in the goats showed a dose-dependent relationship. The response in the voles was obtained by acetate and propionate, but preparations in the mice were ineffective in response to volatile fatty acids. 4. 4. The results indicate that the pancreatic digestive enzyme secretory function in voles resembles that of ruminants.

Changes induced by Gramoxon ® in tissue phospholipids and phospholipid fatty acids in mouse and guinea-pig

1. 1. Following administration of the LD 50 or the LD 100 of Gramoxon ® (PQ), the phospholipids (PL) of the lung, liver and kidney were separated and both the PLs and the fatty acids isolable from them were examined quantitatively. 2. 2. The different doses of PQ caused different changes of the saturated and unsaturated fatty acids in the various organs. 3. 3. The changes in the PL unsaturated fatty acids point to PQ-induced lipid peroxidation enhancement and membrane damage.

Inhibition of lymphocyte capping by fatty acids in mouse and man.

Lipid-enriched diets have been related to a high cancer incidence in experimental animals for many years, and more recently, to assorted defects on the immune response. We investigated the effect of incubating human or murine (C3H/HEJ) lymphocytes with saturated (16:0) and unsaturated (18:1, 18:2, 18:3, 20:4) fatty acids (12 micrograms for each 10(7) cells), on the ability to cap with antihuman or antimouse anti-IgM, mu-chain specific antibody. Capping was also tested in obese (ob/ob, C57BL/6J) mice. Capping at 30 and 60 min was reduced by fatty acid incubation to 10-30% of control values in humans (p less than .001), and to 30% of control values in mice (p less than .01), regardless of degree of unsaturation. ob/ob capped normally. A lymphocyte membrane effect caused by fatty acids is observed in these experiments. Whether this is related to the dysimmunity caused by lipid diets cannot be assessed from our data, especially since all fatty acids, regardless of unsaturation, reduced the capping phenomenon.

Beta-Adrenergic Blocking Activity of Yersinia pestis Murine Toxin

Yersinia pestis plague murine toxin has been found to inhibit the mobilization of free fatty acids in mice in a manner similar to that of beta-adrenergic blocking agents. The blockage is detectable 75 min after injection of the toxin (1 to 2 mean lethal doses). The degree of inhibition was directly correlated with the toxicity of a given toxin preparation. Agents such as cholera toxin or glucagon, with apparently distinct receptors from beta-adrenergic receptors, stimulated adenylate cyclase and lipolysis and effectively modified toxicity. Likewise, cyclic adenosine 3',5'-monophosphate bypassed the toxin block and antagonized toxicity. Energy-rich compounds such as fatty acids, organic acids, and glucose effectively modified the intoxication process. The biological activity of plague toxin showed profound temperature sensitivity. Mice placed at 5 degrees C were highly susceptible to the effects of the toxin, whereas mice placed at 37 degrees C were totally resistant to intoxication. Results showed that plague toxin cannot block epinephrine-induced mobilization of free fatty acids in mice placed at 37 degrees C. These studies suggested that plague toxin acts at the receptor level in a manner similar to that of beta-adrenergic blocking agents. A complete, analogous activity was shown between toxin and known beta-adrenergic antagonists in their effect on beta-adrenergic agonist action in stimulating lipolysis. It is hypothesized that, since toxin shows no in vitro activity, it is in some way modified in animals.

The Relationship between Summated Tissue Respiration and Metabolic Rate in the Mouse and Dog

The Relationship between Summated Tissue Respiration and Metabolic Rate in the Mouse and Dog