The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Open accessAbstract
Lipid homeostasis in vertebrate cells is regulated by a family of membrane-bound transcription factors designated sterol regulatory element-binding proteins (SREBPs).SREBPs directly activate the expression of more than 30 genes dedicated to the synthesis and uptake of cholesterol, fatty acids, triglycerides, and phospholipids, as well as the NADPH cofactor required to synthesize these molecules (1-4).In the liver, three SREBPs regulate the production of lipids for export into the plasma as lipoproteins and into the bile as micelles.The complex, interdigitated roles of these three SREBPs have been dissected through the study of ten different lines of gene-manipulated mice.These studies form the subject of this review.
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“By contrast, Srebp-1c is transcribed at extremely high levels in response to insulin (6, 28)”
From miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling (2011) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“As SREBPs contain an SRE in their promoter region, they induce their own expression in a positive feedback mechanism4,18.”
From Haploid genetic screens identify SPRING/C12ORF49 as a determinant of SREBP signaling and cholesterol metabolism (2020) · cites this paper as [4]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“An additional level of regulation of the genes involved in cholesterol uptake and synthesis is provided by SREBP signaling, in which low cellular sterol levels lead to the SCAP-mediated trafficking of SREBP proteins from the ER to the Golgi, where they are cleaved by resident proteases (encoded by MBTPS1 and MBTPS2) to release and activate their transcription factor domains[7,8].”
From Genome-scale CRISPR screening for modifiers of cellular LDL uptake (2021) · cites this paper as [7]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“likely due to overlapping functions allowing one gene to compensate for loss of the other[7]”
From Genome-scale CRISPR screening for modifiers of cellular LDL uptake (2021) · cites this paper as [7]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Two transcription factor families with opposing actions – the liver-X receptors (LXRs) and the sterol regulatory element-binding proteins (SREBPs) – are the main orchestrators of this balance (Hong and Tontonoz, 2014; Horton et al., 2002).”
From Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP (2017) · cites this paper as Horton et al., 2002
Experimental — accuracy not yet measured
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In the citing paper
“In the liver, SREBP1c is the prominent SREBP1 isoform and primarily controls fatty acid synthesis and mobilization, while SREBP2 controls cholesterol biosynthesis and lipoprotein uptake [12,13].”
From Loss of the E3 ubiquitin ligase MARCHF6 alters hepatic lipid metabolism and drives spontaneous hepatosteatosis (2026) · cites this paper as [12]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The intracellular cholesterol economy is largely regulated by the sterol response element binding protein (SREBPs), a group of transcription factors that regulate genes involved in the biosynthesis of cholesterol and fatty acids (13).”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [13]
The cited source says what the claim attributes to it.
In the citing paper
“SREBP1a and SREBP1c are responsible for fatty acid metabolism and SREBP2 primarily for cholesterol synthesis through increasing the expression of HMG-CoA reductase (HMGCR) [32].”
From HIV-TAT dysregulates microglial lipid metabolism through SREBP2/miR-124 axis: Implication of lipid droplet accumulation microglia in NeuroHIV (2025) · cites this paper as [32]
The cited source says what the claim attributes to it.
In the citing paper
“However, SREBPs not only activate cholesterol synthesis but also fatty acid and phospholipid synthesis (2).”
From Expression of miR-33 from an SREBP2 Intron Inhibits Cholesterol Export and Fatty Acid Oxidation* (2010) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“Genes involved in its synthesis are coordinately up-regulated by the action of SREBP transcription factors (2).”
From Expression of miR-33 from an SREBP2 Intron Inhibits Cholesterol Export and Fatty Acid Oxidation* (2010) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“SREBP-1c regulates the transcription of genes involved in fatty acid metabolism, such as fatty acid synthase (FASN) (5–7).”
From miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling (2011) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“SREBP-2 regulates the transcription of cholesterol-related genes, such as 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR), which catalyzes a rate-limiting step in cholesterol biosynthesis, and the low-density lipoprotein receptor (LDLr), which imports cholesterol from the blood (5–7).”
From miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling (2011) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“The sterol-regulatory element binding proteins (SREBP) are central transcriptional regulators of lipid metabolism.”
From Haploid genetic screens identify SPRING/C12ORF49 as a determinant of SREBP signaling and cholesterol metabolism (2020) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“The SREBP pathway is activated when cellular cholesterol levels decline as a means to increase cholesterol synthesis and uptake (4).”
From A MARCH6 and IDOL E3 Ubiquitin Ligase Circuit Uncouples Cholesterol Synthesis from Lipoprotein Uptake in Hepatocytes (2016) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“The released N-terminal SREBP-1 and −2 transcriptional domains translocate to the nucleus to activate transcriptional programs that promote fatty acid and cholesterol biosynthesis, respectively8.”
From Hepatic SREBP signaling requires SPRING to govern systemic lipid metabolism in mice and humans (2023) · cites this paper as [8]
In the citing paper
“The cellular signal driving this increased hepatic de novo lipogenesis can most likely be attributed to hyperinsulinemia promoting increased expression of the sterol regulatory element binding protein-1c in the liver, which coordinately regulates transcription of all of the key enzymes involved in lipogenesis (24).”
From The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome (2007) · cites this paper as [24]
In the citing paper
“Recently, 2 additional transcription factors, X-box binding protein 1 (XBP1) and CHO response element-binding protein (ChREBP), have been identified as inducers of hepatic lipogenesis in response to ingested CHOs (eg, fructose and glucose) that is independent of insulin.431,432”
From Triglycerides and Cardiovascular Disease: A Scientific Statement From the American Heart Association (2011) · cites this paper as [431]
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Metadata
- Authors
- Horton, J. D., Goldstein, J. L., & Brown, M. S.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Horton, Jay D.
- Venue
- Journal of Clinical Investigation
- Published
- 2002-05-01
- Volume
- 109
- Issue
- 9
- Pages
- 1125-1131
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W4252021281
- Cited by
- 4,092
- References
- 47
- Citations by year
- 2026: 149 · 2025: 178 · 2024: 191 · 2023: 215 · 2022: 211 · 2021: 210 · 2020: 263 · 2019: 217 · 2018: 212 · 2017: 206 · 2016: 199 · 2015: 180 · 2014: 184 · 2013: 180 · 2012: 142
- FWCI
- 104.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Funders
- W. M. Keck Foundation
- American Heart Association
- National Institutes of Health (HL20948)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- SREBP, cholesterol biosynthesis, fatty acid synthesis, lipid homeostasis, liver, transcription factors, NADPH, triglyceride synthesis, phospholipid synthesis, bile micelles, knockout mice
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