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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets.

BACKGROUND: Hypertriglyceridemia is associated with increased risk of cardiovascular disease. Until recently, the importance of hepatic de novo lipogenesis ( DNL) in contributing to hypertriglyceridemia was difficult to assess because of methodologic limitations. OBJECTIVE: We evaluated the extent of the contribution by DNL to different conditions associated with hypertriglyceridemia. DESIGN: After 5 d of an isoenergetic high-fat, low-carbohydrate diet, fasting DNL was measured in normoinsulinemic (<or= 85 pmol/L) lean (n = 9) and obese (n = 6) and hyperinsulinemic (>or= 115 pmol/L) obese (n = 8) subjects. Fasting DNL was measured after a low-fat, high-carbohydrate diet in normoinsulinemic lean (n = 5) and hyperinsulinemic obese (n = 5) subjects. Mass isotopomer distribution analysis was used to measure the fraction of newly synthesized fatty acids in VLDL-triacylglycerol. RESULTS: With the high-fat, low-carbohydrate diet, hyperinsulinemic obese subjects had a 3.7-5.3-fold higher fractional DNL (8.5 +/- 0.7%) than did normoinsulinemic lean (1.6 +/- 0.5%) or obese (2.3 +/- 0.3%) subjects. With the low-fat, high-carbohydrate diet, normoinsulinemic lean and hyperinsulinemic obese subjects had similarly high fractional DNL (13 +/- 5.1% and 12.8 +/- 1.4%, respectively). Compared with baseline, consumption of the high-fat, low-carbohydrate diet did not affect triacylglycerol concentrations. However, after the low-fat, high-carbohydrate diet, triacylglycerols increased significantly and DNL was 5-6-fold higher than in normoinsulinemic subjects consuming a high-fat diet. The increase in triacylglycerol after the low-fat, high-carbohydrate diet was correlated with fractional DNL (P < 0.01), indicating that subjects with high DNL had the greatest increase in triacylglycerols. CONCLUSIONS: These results support the concept that both hyperinsulinemia and a low-fat diet increase DNL, and that DNL contributes to hypertriglyceridemia.[1]

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