Betaine supplementation to rats alleviates disturbances induced by high-fat diet: pleiotropic effects in model of type 2 diabetes.

Betaine is a biologically active compound exerting beneficial effects in the organism, however, the exact mechanisms underlying its action are not fully elucidated. The present study aimed to explore, whether betaine alleviates disorders induced by feeding rats a high-fat diet (HFD). Rats were divided into 3 groups: control, fed an HFD and fed an HFD and receiving betaine (2% water solution for 8 weeks). Betaine improved glucose tolerance, decreased blood levels of non-esterified fatty acids and prevented lipid accumulation in the skeletal muscle of rats on an HFD. Betaine reduced activities of blood alanine aminotransferase, blood levels of bilirubin and hepatic lipid content. Expression of fatty acid synthase in the liver and the skeletal muscle was decreased in response to feeding an HFD, and this effect was deepened by betaine in the muscle tissue. Hepatic and muscular expression of genes related to insulin signaling were unchanged in HFD-fed rats. Lipolysis stimulated by epinephrine (an adrenergic receptor agonist), forskolin (an activator of adenylate cyclase), dibutyryl-cAMP (an activator of protein kinase A) and DPCPX (an adenosine A1 receptor antagonist) was diminished in the adipocytes of rats fed an HFD, however, this effect was alleviated by betaine. Moreover, blood leptin levels in HFD-fed rats were elevated, whereas leptinemia have normalized by betaine supplementation. Betaine prevented the increase in expression of N-methyl D-aspartate receptors in the hippocampus and in the cerebral cortex. These results indicate that betaine positively affects the insulin-sensitive tissues: liver (hepatoprotective effects), skeletal muscle (reduced lipid accumulation) and adipose tissue (a rise in lipolysis), which is associated with improved insulin sensitivity. Betaine-induced prevention of hyperleptinemia indicates restoration of leptin action, and changes in the brain reveal neuroprotective properties. Our results show that betaine induces positive changes in HFD-fed rats, its action is pleiotropic and involves different tissues.

Depleted uranium dust from fired munitions: physical, chemical and biological properties.

This paper reports physical, chemical and biological analyses of samples of dust resulting from munitions containing depleted uranium (DU) that had been live-fired and had impacted an armored target. Mass spectroscopic analysis indicated that the average atom% of U was 0.198 +/- 0.10, consistent with depleted uranium. Other major elements present were iron, aluminum, and silicon. About 47% of the total mass was particles with diameters <300 microm, of which about 14% was <10 microm. X-ray diffraction analysis indicated that the uranium was present in the sample as uranium oxides-mainly U3O7 (47%), U3O8 (44%) and UO2 (9%). Depleted uranium dust, instilled into the lungs or implanted into the muscle of rats, contained a rapidly soluble uranium component and a more slowly soluble uranium component. The fraction that underwent dissolution in 7 d declined exponentially with increasing initial burden. At the lower lung burdens tested (<15 microg DU dust/lung) about 14% of the uranium appeared in urine within 7 d. At the higher lung burdens tested (~80-200 microg DU dust/lung) about 5% of the DU appeared in urine within 7 d. In both cases about 50% of that total appeared in urine within the first day. DU implanted in muscle similarly showed that about half of the total excreted within 7 d appeared in the first day. At the lower muscle burdens tested (<15 microg DU dust/injection site) about 9% was solubilized within 7 d. At muscle burdens >35 microg DU dust/injection site about 2% appeared in urine within 7 d. Natural uranium (NU) ore dust was instilled into rat lungs for comparison. The fraction dissolving in lung showed a pattern of exponential decline with increasing initial burden similar to DU. However, the decline was less steep, with about 14% appearing in urine for lung burdens up to about 200 microg NU dust/lung and 5% at lung burdens >1,100 microg NU dust/lung. NU also showed both a fast and a more slowly dissolving component. At the higher lung burdens of both DU and NU that showed lowered urine excretion rates, histological evidence of kidney damage was seen. Kidney damage was not seen with the muscle burdens tested. DU dust produced kidney damage at lower lung burdens and lower urine uranium levels than NU dust, suggesting that other toxic metals in DU dust may contribute to the damage.