Research
Hormonal
Insulin signaling promotes lipid synthesis and glucose storage by upregulating SREBP-1c and ChREBP, while simultaneously repressing gluconeogenic genes via the inhibition of FOXO transcription factors.
Insulin acts as a master switch for energy storage. When insulin is high (after eating), it turns on genes that store fat and glucose, and turns off genes that produce new glucose. This is why high-insulin states favor fat storage.
StrongSupportsVERY_HIGH confidence
SREBP-1c acts as an important mediator of insulin action... Overexpression of a dominant negative form of SREBP-1c counteracts insulin-mediated induction of the expression of liver pyruvate kinase (L-PK), spot 14 (S14), and fatty acid synthase (FAS)... Insulin also negatively regulates transcription, particularly that of genes involved in hepatic glucose production... FOXOs... are phosphorylated by Akt-1 upon insulin-mediated activation of the PI3K pathway... Phosphorylated FOXO has a high affinity for protein 14-3-3, which relocates FOXO from the nucleus to the cytosol.
Why this rating
High-quality review of molecular mechanisms with specific examples of gene regulation.
Source
Transcriptional Regulation of Metabolism
Béatrice Desvergne et al. · Physiological Reviews · 2006
DOI 10.1152/physrev.00025.2005
narrative_reviewCited 897×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Transcriptional regulation by nuclear receptors (specifically PPARs, LXRs, and SREBPs) and transcription factors (ChREBP, FOXOs) serves as the primary long-term mechanism for maintaining metabolic homeostasis by coordinating glucose, lipid, and amino acid metabolism in response to fasting and feeding cycles.Strong
- High glucose levels independently regulate gene expression through the transcription factor ChREBP, which is activated by glucose metabolites (xylulose 5-phosphate) to promote lipogenesis and glycolysis, even in the absence of insulin.Good
- Fasting and low glucose levels trigger transcriptional changes that promote gluconeogenesis and fatty acid oxidation via the activation of transcription factors like CREB, PGC1, and PPARs, counteracting insulin's effects.Good
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