Tissue specific induction of ChREBP isoforms in carbohydrate refed mice and their impact on lipogenesis (642.8)

Background: Carbohydrate response element binding protein alpha (ChREBPα) is a transcription factor involved in carbohydrate (CHO) induced de novo lipogenesis. Recently, a novel isoform (ChREBPβ) has been discovered and the purpose of this study was to determine the effect of 1) obesity, and 2) different CHO on ChREBPβ induction and transcriptional activity. Methods: For the effect of obesity, mice were fed a high‐fat diet for 12 weeks after which liver mRNA and protein expression of ChREBPα and –β were assessed. To determine the effect of dietary CHO on ChREBPα and –β, mice were fasted for 24 hours and refed a high glucose, sucrose, or fructose diet for 12 hours. Tissues were collected to assess changes in lipogenic induction as well as ChREBPα and ChREBPβ. HEK293 cells were transfected with either ChREBPα or ‐β and treated with either 25mM glucose or fructose for 24 hours and differences in lipogenic activity. Results: ChREBPα mRNA was not affected by obesity, however ChREBPβ mRNA was 3.8±0.6 fold higher than chow‐fed mice. Unexpectedly, ChREBPα decreased after all three CHO diets whereas ChREBPβ increased in all tissues assessed except muscle. In liver, sucrose refeeding caused the largest increase in ChREBPβ expression followed by fructose, then glucose (24.4±11.1, 17.8±9.5, and 10.1±3.2). In HEK cells, ChREBPβ expression was also associated with glucose‐induced lipogenic gene expression and not ChREBPα. Conclusions: ChREBPα and ChREBPb can be detected separately and their induction is detectible in the liver and other peripheral tissues of carbohydrate re‐fed mice. ChREBPβ expression appears to be responsible for carbohydrate‐induced lipogenic gene induction whereas ChREBPα is likely responsible for inducing ChREBPβ. Grant Funding Source : Supported by Aniara Research Grant