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Biomedical subjects

Ichiro Tokimitsu

Publications and source records attributed to Ichiro Tokimitsu.

41 records · Page 3Linked to original sources

Dietary alpha-linolenic acid-rich diacylglycerols reduce body weight gain accompanying the stimulation of intestinal beta-oxidation and related gene expressions in C57BL/KsJ-db/db mice.

Dietary fat contributes to the development of obesity. We examined the effect of dietary diacylglycerol (DG), which is a minor component of edible oils, on the development of obesity and expression of genes involved in energy homeostasis in C57BL/KsJ-db/db mice. Mice were fed diets containing either 14 g/100 g (%) triacylglycerol (TG), 10% TG + 4% alpha-linolenic acid-rich TG (ALATG), or 10% TG + 4% alpha-linolenic acid-rich diacylglycerol (ALADG) for 1 mo. Mice fed ALADG, but not ALATG had less body weight gain and higher rectal temperature than the TG-fed controls. These effects were accompanied by up-regulation of acyl-CoA oxidase, medium-chain acyl-CoA dehydrogenase, fatty acid binding protein, and uncoupling protein (UCP)-2 mRNA and beta-oxidation activity in the small intestine. In contrast, the treatments did not affect beta-oxidation and related gene expressions in the liver or UCP-3 mRNA level in skeletal muscle. These results indicate that stimulation of lipid metabolism in the small intestine might be closely related to the antiobesity and thermogenic effects of dietary DG. In addition, structural differences between DG and TG, not variations in the composition of fatty acids, are responsible for the different effects of the lipids.

Acyl-CoA Dehydrogenases↗

Alpha-monoisostearyl glyceryl ether enhances percutaneous penetration of indometacin in-vivo.

Molecules that reversibly remove the barrier resistance of skin enhance penetration. alpha-Monoisostearyl glyceryl ether (GE-IS) is a novel compound that can be used as a non-ionic surfactant and increases percutaneous penetration of indometacin in rat abdominal skin in-vitro. The present study investigated GE-IS-induced enhancement of indometacin penetration in-vivo. When 1% GE-IS in propylene glycol was applied to rat abdominal skin, serum and muscle concentrations of indometacin increased markedly. Anti-inflammatory activities of test solutions containing both indometacin and GE-IS were investigated in experimental models of acute and chronic inflammation. Application of indometacin with GE-IS to the skin produced greater inhibitory effects on carrageenan-induced rat paw oedema, UV-induced erythema in guinea-pigs, and adjuvant arthritis in rats, compared with application of indometacin alone. The results suggest that GE-IS enhances penetration in-vivo and improves the anti-inflammatory effects of indometacin in animal models. Thus, GE-IS might contribute to the development of cosmetic or medical formulations to improve transfer of bioactive substances to hypodermal sites.

Administration, Cutaneous↗

Green coffee bean extract and its metabolites have a hypotensive effect in spontaneously hypertensive rats.

The effects of a water-soluble green coffee bean extract (GCE) on blood pressure were investigated using spontaneously hypertensive rats (SHR). There was a dose-dependent reduction in blood pressure after a single ingestion (180 to 720 mg/kg, p.o.) or long-term ingestion (0.25 to 1% diet for 6 weeks) of GCE. A single oral ingestion (50 to 200 mg/kg) of 5-caffeoylquinic acid (5-CQA), the major component of GCE, dose-dependently decreased blood pressure, suggesting that 5-CQA is involved in the hypotensive effect of GCE in SHR. Because significant increases in caffeic acid (CA) or ferulic acid (FA) were detected in plasma after oral ingestion of 5-CQA in SHR, these acids (2.5, 5,10 micromol/kg) were intravenously injected into SHR under anesthesia and the carotid arterial pressure was measured. Of the two components, FA had a stronger depressor effect than CA. The depressor effect of FA (50 mg/kg, p.o.) was attenuated by the concurrent injection of atropine sulfate (5 mg/kg, s.c.), suggesting that the hypotensive effect of FA in SHR might be mediated via the muscarinic acetylcholine receptors. These findings indicate that oral ingestion of GCE or 5-CQA decreases blood pressure in SHR, and that FA, which is a metabolite of 5-CQA, is a candidate hypotensive component.

Administration, Oral↗

Anti-obesity effect of dietary diacylglycerol in C57BL/6J mice: dietary diacylglycerol stimulates intestinal lipid metabolism.

We examined the long-term effects of dietary diacylglycerol (DG) and triacylglycerol (TG) with similar fatty acid compositions on the development of obesity in C57BL/6J mice. We also analyzed the expression of genes involved in lipid metabolism at an early stage of obesity development in these mice. Compared with mice fed the high-TG diet, mice fed the high-DG diet accumulated significantly less body fat during the 8-month study period. Within the first 10 days, dietary DG stimulated beta-oxidation and lipid metabolism-related gene expression, including acyl-CoA oxidase, medium-chain acyl-CoA dehydrogenase, and uncoupling protein-2 in the small intestine but not in the liver, skeletal muscle, or brown adipose tissue, suggesting the predominant contribution of intestinal lipid metabolism to the effects of DG. Furthermore, analysis of digestion products of [(14)C]DG and those of [(14)C]TG revealed that the radioactivity levels detected in fatty acid, 1-monoacylglycerol, and 1,3-DG in intestinal mucosa were significantly higher after intrajejunal injection of DG rather than TG. Thus, dietary DG reduces body weight gain that accompanies the stimulation of intestinal lipid metabolism, and these effects may be related to the characteristic metabolism of DG in the small intestine.

Animals↗

Effect of phytosterols in dietary diacylglycerol on atherosclerosis in cholesterol-fed rabbits.

OBJECTIVE: The present study investigated the effects of phytosterols (PS) in combination with diacylglycerol (DAG) versus PS in combination with triacylglycerol (TAG) on serum lipids and atherosclerosis in cholesterol-fed rabbits. METHODS: Cholesterol-fed (0.3%) New Zealand white rabbits were treated with a control diet, a 0.3% PS and 7% TAG diet, or a 0.3% PS and 7% DAG diet for 14 wk. RESULTS: Serum total cholesterol level in the PS/DAG group was statistically lower than that in the control and PS/TAG groups, whereas serum high-density lipoprotein cholesterol and triacylglycerol levels were not statistically different between these two groups. The ratio of the atherosclerotic lesion area and the mean thickness of the intima in the aortas of the PS/DAG group were statistically lower than those of the control group, whereas there was no statistical difference between the PS/TAG and control groups. In particular, the ratio of the lesion area in the abdominal aorta and the mean thickness of the intima in the thoracic and total aortas of the PS/DAG group were statistically lower than those of the PS/TAG group. The ratio of the atherosclerotic lesion area and the mean thickness of the intima in the aortas correlated positively with total cholesterol exposure level. CONCLUSIONS: These findings suggested that PS in combination with DAG as opposed to TAG prevents the development of atherosclerosis via a decrease in total cholesterol exposure level and might be useful as a dietary oil for the prevention of atherosclerosis.

Animals↗