Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/8306
Title: Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1.
Author: Kim, Jae Bum
Sarraf, Pasha
Wright, Margaret
Yao, Kwok M.
Mueller, Elisabetta
Solanes Garcia, Gemma
Lowell, Bradford B.
Spiegelman, Bruce M.
Keywords: Àcids grassos
Leptina
Insulina
Metabolisme energètic
Expressió genètica
ADD1/SREBP1
Fatty acid synthetase
Leptin
Nutritional changes
Insulin
Issue Date: 1998
Publisher: American Society for Clinical Investigation
Abstract: The ability to regulate specific genes of energy metabolism in response to fasting and feeding is an important adaptation allowing survival of intermittent food supplies. However, little is known about transcription factors involved in such responses in higher organisms. We show here that gene expression in adipose tissue for adipocyte determination differentiation dependent factor (ADD) 1/sterol regulatory element binding protein (SREBP) 1, a basic-helix-loop-helix protein that has a dual DNA-binding specificity, is reduced dramatically upon fasting and elevated upon refeeding; this parallels closely the regulation of two adipose cell genes that are crucial in energy homeostasis, fatty acid synthetase (FAS) and leptin. This elevation of ADD1/SREBP1, leptin, and FAS that is induced by feeding in vivo is mimicked by exposure of cultured adipocytes to insulin, the classic hormone of the fed state. We also show that the promoters for both leptin and FAS are transactivated by ADD1/SREBP1. A mutation in the basic domain of ADD1/SREBP1 that allows E-box binding but destroys sterol regulatory element-1 binding prevents leptin gene transactivation but has no effect on the increase in FAS promoter function. Molecular dissection of the FAS promoter shows that most if not all of this action of ADD1/SREBP1 is through an E-box motif at -64 to -59, contained with a sequence identified previously as the major insulin response element of this gene. These results indicate that ADD1/SREBP1 is a key transcription factor linking changes in nutritional status and insulin levels to the expression of certain genes that regulate systemic energy metabolism.
Note: Reproducció del document publicat a http://dx.doi.org/10.1172/JCI1411
It is part of: Journal of Clinical Investigation, 1998, vol. 101, núm. 1, p. 1-9.
URI: http://hdl.handle.net/2445/8306
ISSN: 0021-9738
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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