ArticleMolecular and cellular biology1999
ADD1/SREBP-1c is required in the activation of hepatic lipogenic gene expression by glucose.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers.
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151 citing papers in PubMed, 546 citations in OpenAlex.
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- Insulin-Responsive Transcription Factors.Biomolecules · 2021Review
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- The Interplay between Insulin Resistance, Inflammation, Oxidative Stress, Base Excision Repair and Metabolic Syndrome in Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2021Review
- Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis.Cell metabolism · 2021Article
- A potential probiotic bacterium for antipsychotic-induced metabolic syndrome: mechanisms underpinning how Akkermansia muciniphila subtype improves olanzapine-induced glucose homeostasis in mice.Psychopharmacology · 2021Article
- Hepatic transcriptional responses to fasting and feeding.Genes & development · 2021Review
91 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcription of genes encoding proteins involved in the hepatic synthesis of lipids from glucose is strongly stimulated by carbohydrate feeding. It is now well established that in the liver, glucose is the main activator of the expression of this group of genes, with insulin having only a permissive role. While ADD1/SREBP-1 has been implicated in lipogenic gene expression through temporal association with food intake and ectopic gain-of-function experiments, no genetic evidence for a requirement for this factor in glucose-mediated gene expression has been established. We show here that the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP, establishing a link between this transcription factor and carbohydrate availability. Using adenovirus-mediated transfection of a powerful dominant negative form of ADD1/SREBP-1c in rat hepatocytes, we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression. These results demonstrate that ADD1/SREBP-1c plays a crucial role in mediating the expression of lipogenic genes induced by glucose and insulin.
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