Involvement of a Unique Carbohydrate-responsive Factor in the Glucose Regulation of Rat Liver Fatty-acid Synthase Gene Transcription

Caterina Rufo, Margarita Teran-Garcia, Manabu T. Nakamura, Seung-Hoi Koo, Howard C. Towle, Steven D. Clarke

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Refeeding carbohydrate to fasted rats induces the transcription of genes encoding enzymes of fatty acid biosynthesis, e.g. fatty-acid synthase (FAS). Part of this transcriptional induction is mediated by insulin. An insulin response element has been described for the fatty-acid synthase gene region of -600 to +65, but the 2-3-fold increase in fatty-acid synthase promoter activity attributable to this region is small compared with the 20-30-fold induction in fatty-acid synthase gene transcription observed in fasted rats refed carbohydrate. We have previously reported that the fatty-acid synthase gene region between -7382 and -6970 was essential for achieving high in vivo rates of gene transcription. The studies of the current report demonstrate that the region of -7382 to -6970 of the fatty-acid synthase gene contains a carbohydrate response element (CHO-REFAS) with a palindrome sequence (CATGTGn5GGCGTG) that is nearly identical to the CHO-RE of the L-type pyruvate kinase and S14 genes. The glucose responsiveness imparted by CHO-REFAS was independent of insulin. Moreover, CHO-REFAS conferred glucose responsiveness to a heterologous promoter (i.e. L-type pyruvate kinase). Electrophoretic mobility shift assays demonstrated that CHO-REFAS readily bound a unique hepatic ChoRF and that CHO-REFAS competed with the CHO-RE of the L-type pyruvate kinase and S14 genes for ChoRF binding. In vivo footprinting revealed that fasting reduced and refeeding increased ChoRF binding to CHO-REFAS. Thus, carbohydrate responsiveness of rat liver fatty-acid synthase appears to require both insulin and glucose signaling pathways. More importantly, a unique hepatic ChoRF has now been shown to recognize glucose responsive sequences that are common to three different genes: fatty-acid synthase, L-type pyruvate kinase, and S14.

Original languageEnglish
Pages (from-to)21969-21975
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number24
DOIs
Publication statusPublished - 2001 Jun 15
Externally publishedYes

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Fatty Acid Synthases
Transcription
Liver
Rats
Genes
Carbohydrates
Glucose
Pyruvate Kinase
Insulin
Response Elements
Inverted Repeat Sequences
Electrophoretic mobility
Gene encoding
Biosynthesis
Electrophoretic Mobility Shift Assay
Assays
Fatty Acids
Fasting
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Involvement of a Unique Carbohydrate-responsive Factor in the Glucose Regulation of Rat Liver Fatty-acid Synthase Gene Transcription. / Rufo, Caterina; Teran-Garcia, Margarita; Nakamura, Manabu T.; Koo, Seung-Hoi; Towle, Howard C.; Clarke, Steven D.

In: Journal of Biological Chemistry, Vol. 276, No. 24, 15.06.2001, p. 21969-21975.

Research output: Contribution to journalArticle

Rufo, Caterina ; Teran-Garcia, Margarita ; Nakamura, Manabu T. ; Koo, Seung-Hoi ; Towle, Howard C. ; Clarke, Steven D. / Involvement of a Unique Carbohydrate-responsive Factor in the Glucose Regulation of Rat Liver Fatty-acid Synthase Gene Transcription. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 24. pp. 21969-21975.
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