title: Tissue Specific Effects of Dietary Carbohydrates and Obesity on ChREBPα and ChREBPβ Expression.
abstract: Carbohydrate response element binding protein (ChREBP) regulates insulin-independent de novo lipogenesis. Recently, a novel ChREBPβ isoform was identified. The purpose of the current study was to define the effect of dietary carbohydrates (CHO) and obesity on the transcriptional activity of ChREBP isoforms and their respective target genes. Mice were subjected to fasting-refeeding of high-CHO diets. In all three CHO-refeeding groups, mice failed to induce ChREBPα, yet ChREBPβ increased 10- to 20-fold. High-fat fed mice increased hepatic ChREBPβ mRNA expression compared to chow-fed along with increased protein expression. To better assess the independent effect of fructose on ChREBPα/β activity, HepG2 cells were treated with fructose ± a fructose-1,6-bisphosphatase inhibitor to suppress gluconeogenesis. Fructose treatment in the absence of gluconeogenesis resulted in increased ChREBP activity. To confirm the existence of ChREBPβ in human tissue, primary hepatocytes were incubated with high-glucose and the expression of ChREBPα and -β was determined. As with the animal models, glucose induced ChREBPβ expression while ChREBPα was decreased. Taken together, ChREBPβ is more responsive to changes in dietary CHO availability than the -α isoform. Diet-induced obesity increases basal expression of ChREBPβ, which may increase the risk of developing hepatic steatosis, and fructose-induced activation is independent of gluconeogenesis.
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, TX, 79409, USA.
authors.forename: Alexis D
authors.initials: AD
authors.lastname: Stamatikos
authors.affiliation: Department of Agricultural, Food and Nutritional Sciences, Alberta Diabetes Institute, University of Alberta, Edmonton, AB, T6G 2S2, Canada.
authors.forename: Robin P
authors.initials: RP
authors.lastname: da Silva
authors.affiliation: Department of Surgery, Surgical-Medical Research Institute, University of Alberta, Edmonton, AB, T6G 2S2, Canada.
authors.forename: Jamie T
authors.initials: JT
authors.lastname: Lewis
authors.affiliation: Department of Surgery, Surgical-Medical Research Institute, University of Alberta, Edmonton, AB, T6G 2S2, Canada.
authors.forename: Donna N
authors.initials: DN
authors.lastname: Douglas
authors.affiliation: Department of Surgery, Surgical-Medical Research Institute, University of Alberta, Edmonton, AB, T6G 2S2, Canada.
authors.forename: Norman M
authors.initials: NM
authors.lastname: Kneteman
authors.affiliation: Department of Agricultural, Food and Nutritional Sciences, Alberta Diabetes Institute, University of Alberta, Edmonton, AB, T6G 2S2, Canada.
authors.forename: René L
authors.initials: RL
authors.lastname: Jacobs
authors.affiliation: Department of Food Science & Technology, University of Georgia, 100 Cedar St., Athens, GA, 30602, USA. cpaton@uga.edu.|Department of Foods & Nutrition, University of Georgia, Athens, GA, USA. cpaton@uga.edu.
authors.forename: Chad M
authors.initials: CM
authors.lastname: Paton
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D004032:Diet; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000009:adverse effects*; D005632:Fructose / Q000494:pharmacology; D020869:Gene Expression Profiling; D005943:Gluconeogenesis / Q000187:drug effects; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism*; D009928:Organ Specificity / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004040:Dietary Carbohydrates; C116385:MLXIPL protein, human; C506001:Mlxipl protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D005632:Fructose
keywords: De novo lipogenesis; Fasting-refeeding; Fatty liver; Fructose; Gluconeogenesis; Obesity