Replacing dietary glucose with fructose increases ChREBP activity and SREBP-1 protein in rat liver nucleus.
Diets high in fructose cause hypertriglyceridemia and insulin resistance in part due to simultaneous induction of gluconeogenic and lipogenic genes in liver. We investigated the mechanism underlying the unique pattern of gene induction by dietary fructose. Male Sprague-Dawley rats (n=6 per group) were meal-fed (4h/d) either 63% (w/w) glucose or 63% fructose diet. After two weeks, animals were killed at the end of the last meal. Nuclear SREBP-1 was 2.2 times higher in fructose-fed rats than glucose-fed rats. Nuclear FoxO1 was elevated 1.7 times in fructose group, but did not reach significance (P=0.08). Unexpectedly, no difference was observed in nuclear ChREBP between two groups. However, ChREBP DNA binding was 3.9x higher in fructose-fed animals without an increase in xylulose-5-phospate, a proposed ChREBP activator. In conclusion, the gene induction by dietary fructose is likely to be mediated in part by simultaneously increased ChREBP activity, SREBP-1 and possibly FoxO1 protein in nucleus.
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Hyun-Young
HY
Koo
Michio
M
Miyashita
B H Simon
BH
Cho
Manabu T
MT
Nakamura
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004032:Diet; D004040:Dietary Carbohydrates / Q000008:administration & dosage* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005632:Fructose / Q000008:administration & dosage* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D050155:Lipogenesis / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010428:Pentosephosphates / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*; D000071161:Forkhead Box Protein O1
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004247:DNA; D004040:Dietary Carbohydrates; D051858:Forkhead Transcription Factors; D005632:Fructose; D005947:Glucose; D009419:Nerve Tissue Proteins; D010428:Pentosephosphates; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; C442825:Mlxipl protein, rat; C497389:Srebf1 protein, rat; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1; C031625:xylulose-5-phosphate