High-fat/low-carbohydrate diets regulate glucose metabolism via a long-term transcriptional loop

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• 作者：Lauren M. Sparks ; Hui Xie ; Robert A. Koza ; R ; all Mynatt ; George A. Bray ; Steven R. Smith
• 关键词：peanut ; Δ ; ¹² fatty acid desaturase ; prokaryotical expression ; function identification
• 刊名：Metabolism
• 出版年：2006
• 出版时间：November 2006
• 年：2006
• 卷：55
• 期：11
• 页码：1457-1463
• 全文大小：204 K

文摘

Insulin sensitivity is characterized by insulin-stimulated glucose metabolism in skeletal muscle. We hypothesized that carbohydrate metabolism and storage might be under transcriptional control. To test this hypothesis, we fed insulin-sensitive males (glucose disposal rate, 14.7 ± 4.1 mg/kg fat-free mass [FFM] per minute) an isoenergetic high-fat/low-carbohydrate diet (HF/LCD) for 3 days with muscle biopsies before and after intervention. Oligonucleotide microarrays revealed a total of 369 genes of 18 861 genes on the arrays were differentially regulated in response to diet (Bonferonni adjusted P < .01). A similar experiment was conducted in mice with a 3-week intervention using a control group and an HF/LCD group to offset the lack of a control group within the human cohort. As part of an analysis of results previously published from this data set, 7 genes in the carbohydrate metabolism pathway changed in response to the HF/LCD, and 3 genes were confirmed by quantitative reverse transcriptase–polymerase chain reaction: fructose-2,6-biphosphatase 3 (PFKFB3), pyruvate dehydrogenase kinase, isoenzyme 4 (PDK4), and glycogen synthase 1 (muscle). In a separate experiment, we fed C57Bl/6J mice an HF/LCD for 3 weeks and found that the same glucose metabolism genes were changed by ~70 % on average. Fructose-2,6-biphosphatase 3 and pyruvate dehydrogenase kinase, isoenzyme 4 increased and glycogen synthase 1 (muscle) decreased. Combined, these results suggest a mechanism whereby HF/LCD regulates the genes necessary for glucose utilization and storage vis-á-vis transcriptional control.