ESSENTIAL ROLE IN VIVO OF UPSTREAM STIMULATORY FACTORS FOR A NORMAL DIETARY RESPONSE OF THE FATTY ACID SYNTHASE GENE IN THE LIVER

摘要: In the liver, transcription of several genes encoding lipogenic and glycolytic enzymes, in particular gene for fatty acid synthase (FAS), is known to be stimulated by dietary carbohydrates. The molecular dissection FAS promoter pointed out critical role an E box motif, located at position −65 with respect start site transcription, mediating glucose- insulin-dependent regulation gene. Upstream stimulatory factors (USF1 USF2) sterol response element binding protein 1 (SREBP1) were shown able interact vitro this box. However, date, relative contributions USFs SREBP1 ex vivo remain controversial. To gain insight into specific roles these factorsin vivo, we have analyzed glucose responsiveness hepatic expression USF1 USF2 knock-out mice. both types mouse lines, defective either or USF2, induction refeeding a carbohydrate-rich diet was severely delayed, whereas almost normal insulin unchanged. Therefore, USF transactivators, especially USF1/USF2 heterodimers, seem essential sustain liver.