Effects of benfluorex on in vivo patterns of insulin resistance induced by diets rich in fat or fructose.
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Animals↗
Biomedical subjects
D A Pan
Publications and source records attributed to D A Pan.
Dietary lipid profile is a determinant of tissue phospholipid fatty acid composition and rate of weight gain in rats.
Modifications in membrane fatty acid composition and insulin action are possible through dietary intervention. We examined the metabolic fate of (n-3) fatty acids in male Wistar rats, using three isocaloric, high fat diets. The ET-L, OL-L and SAF-L diets contained edible tallow, olive oil and safflower oil, respectively, with identical amounts of (n-3) fatty acids as linseed oil. Despite isocaloric feeding, weight gain was lower (P < 0.001) in rats fed the more highly saturated ET-L diet (69 +/- 8 g) than in those fed either the high (n-9) fatty acid OL-L diet (93 +/- 2 g) or the high (n-6) fatty acid SAF-L diet (108 +/- 4 g). Analysis of red quadricep fatty acid composition revealed phospholipid (n-3) fatty acid levels in the ET-L-fed group (21.6 +/- 0.8 g/100 g fatty acids) to be significantly higher than in either the OL-L-fed (17.7 +/- 0.6 g/100 g fatty acids, P < 0.05) or SAF-L-fed (15.3 +/- 0.7 g/100 g fatty acids, P < 0.05) group. A similar pattern was observed in other muscles and white adipose tissue. A follow-up study using 14C-labeled (n-3) fatty acids in the diet showed greater (n-3) fatty acid incorporation in the ET-L-fed group relative to the other two groups and conversely lower 14CO2 production than in the SAF-L-fed group. These results demonstrate that metabolic fate of dietary fatty acids is strongly influenced by the overall fatty acid profile of the diet.(ABSTRACT TRUNCATED AT 250 WORDS)
Adipose Tissue↗
Syndromes of insulin resistance in the rat. Inducement by diet and amelioration with benfluorex.
Insulin resistance, mainly in skeletal muscle, is linked to a cluster of prevalent diseases including NIDDM, dyslipidemias, hypertension, and cardiovascular disease. To determine if an oversupply of lipid is associated with the development of skeletal muscle insulin resistance, we examined the effect of the hypolipidemic agent benfluorex in dietary models of insulin resistance. Adult, male Wistar rats were divided into six groups and maintained for 4 wk on diets high in complex carbohydrate, fructose or fat, with or without 50 mg.kg-1.day-1 of benfluorex, given orally. Insulin action was assessed using a hyperinsulinemic (approximately 100 mU/L) euglycemic clamp, with 2-deoxyglucose tracer for individual tissue evaluation, in chronically cannulated conscious animals. Compared with starch feeding, fructose and fat feeding significantly impaired insulin action at the whole-body level (-46% and -41%, respectively, both P < 0.001), as well as in individual skeletal muscles. Fructose feeding increased circulating TGs (by 80%, P < 0.01) but not skeletal muscle TGs; whereas, fat feeding increased skeletal muscle TGs (by 59%, P < 0.01) but not circulating TGs. With benfluorex, however, diet had no effect on circulating and storage TGs; and development of skeletal muscle insulin resistance in the two diet groups was prevented. Feeding fructose but not fat significantly increased mean arterial BP (by 13%, P < 0.05), an effect prevented by benfluorex. These effects support the hypothesis that the development of muscle insulin resistance in these models is linked to local or systemic oversupply of lipid. These diet models--and the parallel effect of benfluorex on insulin resistance, lipids, and hypertension--may prove useful in the search for the mechanisms that underlie the human disorders associated with insulin resistance.
Analysis of Variance↗
Membrane fatty acid changes during the cell cycle of CV-1 cells.
Monolayers of CV-1 cells were synchronized at the G1/S boundary of the cell cycle by a 24-h 2 mM thymidine blockade. Uptake of tritiated thymidine indicated that the peak DNA synthesis occurred 6-8 h after release from the block and that cell cycle time was 18-20 h. The fatty acid composition of phospholipids extracted from cells at 0, 7, and 18 h postblockade was measured by gas chromatography. The results indicate cyclic changes in membrane fatty acids with a significant increase in long-chain polyunsaturated fatty acids during the DNA synthesis phase (S phase) of the cell cycle.
Animals↗