High-fat/low-carbohydrate diets regulate glucose metabolism via a long-term transcriptional loop.
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 18861 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 approximately 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.
Sparks
Lauren M
LM
Department of Biological Sciences, Louisiana State University and Agricultural and Mechanical College, Baton Rouge, LA, USA.
Xie
Hui
H
Koza
Robert A
RA
Mynatt
Randall
R
Bray
George A
GA
Smith
Steven R
SR
D000328:Adult; D000818:Animals; D002153:Calorimetry, Indirect; D015331:Cohort Studies; D004040:Dietary Carbohydrates / Q000008:administration & dosage* / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006006:Glycogen Synthase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D025481:Phosphofructokinase-2 / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D006006:Glycogen Synthase; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4; D025481:Phosphofructokinase-2; D005947:Glucose