Insulin-independent induction of sterol regulatory element-binding protein-1c expression in the livers of streptozotocin-treated mice.
Insulin and glucose together have been previously shown to regulate hepatic sterol regulatory element-binding protein (SREBP)-1c expression. We sought to explore the nutritional regulation of lipogenesis through SREBP-1c induction in a setting where effects of sugars versus insulin could be distinguished. To do so, mice were insulin depleted by streptozotocin (STZ) administration and subjected to a fasting-refeeding protocol with glucose, fructose, or sucrose. Unexpectedly, the insulin-depleted mice exhibited a marked induction of SREBP-1c on all sugars, and this increase in SREBP-1c was even more dramatic than in the non-STZ-administered controls. The time course of changes in SREBP-1 induction varied depending on the type of sugars in both control and STZ-administered mice. Glucose refeeding gave a peak of SREBP-1c induction, whereas fructose refeeding caused slow and gradual increments, and sucrose refeeding fell between these two responses. Expression of various lipogenic enzymes were also gradually increased over time, irrespective of the types of sugars, with greater intensities in STZ-administered than in nontreated mice. In contrast, induction of hepatic glucokinase and suppression of phoshoenolpyruvate carboxykinase were insulin dependent in an early refed state. These data clearly demonstrate that nutritional regulation of SREBP-1c and lipogenic genes may be completely independent of insulin as long as sufficient carbohydrates are available.
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Takashi
T
Matsuzaka
Hitoshi
H
Shimano
Naoya
N
Yahagi
Michiyo
M
Amemiya-Kudo
Hiroaki
H
Okazaki
Yoshiaki
Y
Tamura
Yoko
Y
Iizuka
Ken
K
Ohashi
Sachiko
S
Tomita
Motohiro
M
Sekiya
Alyssa
A
Hasty
Yoshimi
Y
Nakagawa
Hirohito
H
Sone
Hideo
H
Toyoshima
Shun
S
Ishibashi
Jun-Ichi
J
Osuga
Nobuhiro
N
Yamada
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics*; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005786:Gene Expression Regulation / Q000235:genetics; D005941:Glucokinase / Q000235:genetics; D005905:Glyburide / Q000494:pharmacology; D007700:Kinetics; D020738:Leptin / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D005230:Fatty Acids, Nonesterified; D020738:Leptin; D012333:RNA, Messenger; C497388:Srebf1 protein, mouse; C497391:Srebf2 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors; D014280:Triglycerides; D002784:Cholesterol; D005941:Glucokinase; D005905:Glyburide