GO:0045723 positive regulation of fatty acid biosynthetic process: Regulation, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0045723 describes any process that activates or increases the frequency, rate or extent of fatty acid biosynthesis, a central anabolic pathway in cellular metabolism.
• Key transcription factors such as SREBP1 and PPARγ, and enzymes including ACSL4 and SDHC, are experimentally validated regulators of fatty acid biosynthetic flux.
• Dysregulation of positive regulation of fatty acid biosynthesis contributes to steatohepatitis, hepatocellular carcinoma, colorectal cancer, and triple-negative breast cancer.
• Signaling inputs including IL-18/cGAMP, SIRT1/PGC-1α/PPARα, and USP22-mediated PPARγ stabilization directly modulate this process.
• CRISPR knockout, point mutation, knock-in, and overexpression models enable causal testing of candidate regulators of GO:0045723.
• Combining lipidomics, RNA-seq, and CRISPR screening provides a systems-level view of how positive regulators shape fatty acid biosynthetic output.
Description
Fatty acid biosynthesis is a fundamental anabolic process that supplies acyl chains for membrane lipids, energy storage, and signaling molecules. GO:0045723, positive regulation of fatty acid biosynthetic process, captures the upstream and intracellular events that increase the rate or extent of this pathway. Understanding this term is essential because shifts in fatty acid synthesis underpin metabolic disease, cancer progression, and immune cell function. Researchers studying metabolism, oncology, and immunology increasingly need to identify which genes causally enhance fatty acid biosynthesis and how those genes are themselves regulated. This article integrates the QuickGO definition of GO:0045723 with verified PubMed literature to provide a research-grade overview of the mechanisms, key genes, disease links, and experimental models relevant to this GO term.
positive regulation of fatty acid biosynthetic process At A Glance
| GO ID | GO:0045723 |
|---|---|
| GO term | positive regulation of fatty acid biosynthetic process |
| Ontology | biological_process |
| Synonym | activation of fatty acid biosynthetic process; positive regulation of fatty acid anabolism; positive regulation of fatty acid biosynthesis; positive regulation of fatty acid formation; positive regulation of fatty acid synthesis; stimulation of fatty acid biosynthetic process; up regulation of fatty acid biosynthetic process; up-regulation of fatty acid biosynthetic process; upregulation of fatty acid biosynthetic process |
| Major function | Increases the frequency, rate or extent of fatty acid formation |
| Biological context | Anabolic metabolism, membrane biogenesis, energy storage, cancer and immune cell reprogramming |
| Representative regulators | SREBP1, PPARγ, ACSL4, SDHC, USP22, SIRT1/PGC-1α/PPARα axis |
| Disease relevance | Steatohepatitis, hepatocellular carcinoma, colorectal cancer, triple-negative breast cancer |
What Is GO:0045723?
GO:0045723 is a biological process term defined as any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of fatty acids. In practical terms, it encompasses the molecular events that positively regulate the enzymatic steps converting acetyl-CoA and malonyl-CoA into fatty acyl chains, including transcriptional activation of biosynthetic enzymes, stabilization of rate-limiting enzymes, and signaling cascades that elevate flux through the pathway.
Why Is positive regulation of fatty acid biosynthetic process Important in Cell Biology?
Positive regulation of fatty acid biosynthesis is a metabolic control point that determines how much lipid a cell can produce. In normal physiology, this process supports membrane synthesis and energy storage, but in disease it is frequently hijacked. For example, ACSL4 reprograms fatty acid metabolism in hepatocellular carcinoma via the c-Myc/SREBP1 pathway, and SDHC deficiency promotes metastasis by reprogramming fatty acid metabolism in colorectal cancer. USP22 stabilizes PPARγ to drive lipidome accumulation in hepatocellular carcinoma, while ACSL4-mediated histone hyperacetylation upregulates SNAIL to drive triple-negative breast cancer metastasis. In steatohepatitis, TXNIP/VDUP1 attenuates disease via autophagy and fatty acid oxidation, and formononetin promotes fatty acid β-oxidation through SIRT1/PGC-1α/PPARα. These examples show that GO:0045723 is not a passive housekeeping term but a dynamic, disease-relevant regulatory node.
• Controls the supply of fatty acids for membrane phospholipids and energy storage.
• Is reprogrammed in hepatocellular carcinoma to support tumor growth and survival.
• Promotes metastasis in colorectal cancer when SDHC is deficient.
• Drives triple-negative breast cancer aggressiveness via ACSL4-mediated epigenetic changes.
• Modulates intestinal tolerance through IL-18 and cGAMP signaling.
• Is attenuated by TXNIP/VDUP1 in steatohepatitis, linking autophagy to fatty acid oxidation.
• Can be targeted by natural compounds such as formononetin via SIRT1/PGC-1α/PPARα.
• Represents a therapeutic entry point for metabolic dysfunction-associated steatotic liver disease and cancers.
• Provides a mechanistic explanation for how trans fatty acids influence metabolic regulation.
• Serves as a testable hypothesis for CRISPR screens aimed at identifying novel lipid regulators.
What Happens During positive regulation of fatty acid biosynthetic process?
Transcriptional activation of fatty acid biosynthetic genes
In simple terms: The cell switches on the genes needed to build fatty acids.
A major mechanism of positive regulation is the transcriptional induction of enzymes in the fatty acid biosynthetic pathway. SREBP1 is a central transcription factor that activates lipogenic gene expression, and ACSL4 reprograms fatty acid metabolism in hepatocellular carcinoma via the c-Myc/SREBP1 pathway. This transcriptional arm ensures that the enzymatic machinery for fatty acid formation is available when demand increases.
Stabilization and activation of rate-limiting enzymes
In simple terms: The cell protects and boosts the enzymes that actually make fatty acids.
Beyond transcription, positive regulation can occur through post-translational stabilization of key enzymes. USP22 regulates lipidome accumulation by stabilizing PPARγ in hepatocellular carcinoma, illustrating how deubiquitinase activity can sustain a pro-lipogenic program. Such stabilization increases the effective concentration of regulators that drive fatty acid biosynthesis.
Signaling inputs that increase fatty acid synthesis
In simple terms: External and internal signals tell the cell to make more fat.
Signaling pathways converge on fatty acid biosynthesis to adjust its rate. A metabolic switch orchestrated by IL-18 and the cyclic dinucleotide cGAMP programs intestinal tolerance, demonstrating that immune-derived signals can reshape lipid metabolism. Similarly, formononetin promotes fatty acid β-oxidation to treat non-alcoholic steatohepatitis through the SIRT1/PGC-1α/PPARα pathway, showing that pharmacological modulation of signaling can shift the balance between synthesis and oxidation.
Metabolic reprogramming in cancer and immune cells
In simple terms: Diseased cells rewire fat production to support their behavior.
Positive regulation of fatty acid biosynthesis is frequently reprogrammed in cancer. Deficiency of SDHC promotes metastasis by reprogramming fatty acid metabolism in colorectal cancer, and ACSL4-mediated H3K9 and H3K27 hyperacetylation upregulates SNAIL to drive triple-negative breast cancer metastasis. These findings link GO:0045723 to epigenetic and metastatic programs, underscoring its importance beyond basic metabolism.
Autophagy and fatty acid oxidation crosstalk
In simple terms: The cell's recycling system can influence how much fat it makes or burns.
Autophagy and fatty acid oxidation are interconnected with biosynthetic regulation. TXNIP/VDUP1 attenuates steatohepatitis via autophagy and fatty acid oxidation, indicating that positive regulation of fatty acid biosynthesis must be considered alongside catabolic pathways. The balance between synthesis and oxidation determines net lipid accumulation and cellular stress responses.
Key Genes Involved in GO:0045723 positive regulation of fatty acid biosynthetic process
The following genes and proteins have been experimentally linked to positive regulation of fatty acid biosynthetic process or its dysregulation in disease.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SREBP1 | Transcription factor activating lipogenic genes | Central regulator of fatty acid biosynthesis; target of ACSL4/c-Myc signaling |
| ACSL4 | Long-chain acyl-CoA synthetase; reprograms fatty acid metabolism | Drives hepatocellular carcinoma and TNBC metastasis via SREBP1 and epigenetic changes |
| PPARγ | Nuclear receptor promoting lipid accumulation | Stabilized by USP22 in hepatocellular carcinoma |
| USP22 | Deubiquitinase stabilizing PPARγ | Regulates lipidome accumulation in liver cancer |
| SDHC | Succinate dehydrogenase subunit; metabolic reprogramming | Deficiency promotes metastasis via fatty acid metabolism in colorectal cancer |
| TXNIP/VDUP1 | Redox regulator linked to autophagy and fatty acid oxidation | Attenuates steatohepatitis |
| SIRT1 | NAD+-dependent deacetylase | Part of SIRT1/PGC-1α/PPARα axis modulating fatty acid oxidation |
| PGC-1α | Transcriptional coactivator | Coordinates mitochondrial and lipid metabolism with SIRT1/PPARα |
| PPARα | Nuclear receptor promoting fatty acid oxidation | Mediates formononetin effects in NASH |
| IL-18 | Cytokine involved in intestinal tolerance | Orchestrates metabolic switch with cGAMP |
| cGAMP | Cyclic dinucleotide second messenger | Programs intestinal tolerance via metabolic switch |
| SNAIL | Epithelial-mesenchymal transition transcription factor | Upregulated by ACSL4-mediated histone acetylation in TNBC |
| c-Myc | Oncogenic transcription factor | Upstream regulator of SREBP1 in HCC |
| H3K9ac | Histone acetylation mark | Hyperacetylation linked to ACSL4-driven TNBC metastasis |
| H3K27ac | Histone acetylation mark | Hyperacetylation linked to ACSL4-driven TNBC metastasis |
| trans fatty acids | Dietary fatty acid isomers | Modulate metabolic regulation and fatty acid handling |
How Is positive regulation of fatty acid biosynthetic process Regulated?
Positive regulation of fatty acid biosynthetic process is controlled at multiple levels. Transcriptionally, SREBP1 and PPARγ drive expression of lipogenic enzymes, with ACSL4 acting upstream via c-Myc/SREBP1 in hepatocellular carcinoma and USP22 stabilizing PPARγ. Signaling inputs such as IL-18 and cGAMP can reprogram lipid metabolism in immune contexts, while the SIRT1/PGC-1α/PPARα axis modulates the balance between fatty acid oxidation and synthesis. Dietary factors, including trans fatty acids, also influence metabolic regulation. These layers allow cells to fine-tune fatty acid production in response to nutrients, hormones, and stress.
positive regulation of fatty acid biosynthetic process and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ACSL4 | Hepatocellular carcinoma; TNBC metastasis | Knockout and overexpression in HCC and TNBC cell lines |
| USP22 | Hepatocellular carcinoma lipid accumulation | Knockout and point mutation in liver cancer cells |
| SDHC | Colorectal cancer metastasis | Knockout in colorectal cancer cells |
| TXNIP/VDUP1 | Steatohepatitis | Overexpression and knockout in hepatocytes |
| SIRT1/PGC-1α/PPARα | Non-alcoholic steatohepatitis | Knockout and knock-in in liver models |
Hepatocellular carcinoma and steatohepatitis
In hepatocellular carcinoma, ACSL4 reprograms fatty acid metabolism via the c-Myc/SREBP1 pathway, supporting tumor growth. USP22 stabilizes PPARγ to promote lipidome accumulation in liver cancer. In steatohepatitis, TXNIP/VDUP1 attenuates disease through autophagy and fatty acid oxidation, while formononetin promotes fatty acid β-oxidation via SIRT1/PGC-1α/PPARα to treat non-alcoholic steatohepatitis. These studies show that positive regulation of fatty acid biosynthesis is a double-edged sword in liver disease.
Colorectal cancer metastasis
Deficiency of SDHC promotes metastasis by reprogramming fatty acid metabolism in colorectal cancer. This finding links mitochondrial dysfunction to enhanced fatty acid biosynthetic programs that support metastatic spread, highlighting GO:0045723 as a potential therapeutic target in colorectal cancer.
Triple-negative breast cancer
ACSL4-mediated H3K9 and H3K27 hyperacetylation upregulates SNAIL to drive triple-negative breast cancer metastasis. This epigenetic mechanism connects fatty acid metabolism to epithelial-mesenchymal transition, demonstrating that positive regulation of fatty acid biosynthesis can directly influence metastatic gene programs.
Intestinal immunity and tolerance
A metabolic switch orchestrated by IL-18 and the cyclic dinucleotide cGAMP programs intestinal tolerance. This illustrates that positive regulation of fatty acid biosynthesis is not limited to cancer and metabolic disease but also shapes immune cell function and tissue homeostasis.
From positive regulation of fatty acid biosynthetic process-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of a candidate gene reduce fatty acid biosynthesis? | CRISPR knockout cell line |
| Does a specific mutation alter enzymatic activity? | Point mutation knock-in |
| Does a disease-associated variant affect regulation? | Knock-in of variant allele |
| Where does a regulator localize in the cell? | Tagged knock-in (e.g., GFP) |
| Does overexpression increase lipid accumulation? | Overexpression cell line |
| Which genes regulate fatty acid biosynthesis genome-wide? | CRISPR library screening |
How to Study the positive regulation of fatty acid biosynthetic process Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Lipidomics (LC-MS) | Fatty acid species and abundance | Quantify biosynthetic output after gene perturbation |
| 13C metabolic flux analysis | Rate of fatty acid synthesis | Measure flux through biosynthetic pathway |
| RNA-seq | Gene expression changes | Identify lipogenic transcriptional programs |
| CRISPR knockout screen | Genes required for fatty acid biosynthesis | Discover novel regulators |
| CRISPR activation screen | Genes that increase fatty acid biosynthesis | Identify positive regulators |
| Co-immunoprecipitation | Protein-protein interactions | Study PPARγ, USP22, SREBP1 complexes |
| Fluorescence microscopy | Subcellular localization | Validate tagged knock-in lines |
Lipidomics and metabolic flux analysis
Mass spectrometry-based lipidomics quantifies fatty acid species and can reveal changes in biosynthetic output. Metabolic flux analysis using labeled precursors such as 13C-acetate or 13C-glucose measures the rate of fatty acid synthesis. These methods are essential for validating whether a genetic perturbation affects GO:0045723.
Transcriptomics and RNA-seq
RNA-seq measures expression of lipogenic genes such as SREBP1 targets and PPARγ-responsive genes. In hepatocellular carcinoma, ACSL4 reprograms fatty acid metabolism via c-Myc/SREBP1, and transcriptomic profiling can identify such regulatory networks. Combining RNA-seq with pathway enrichment helps map positive regulators of fatty acid biosynthesis.
CRISPR screening and functional genomics
Genome-wide CRISPR knockout or activation screens can identify genes whose loss or gain alters fatty acid biosynthesis. These screens are particularly useful for discovering novel regulators beyond known candidates like ACSL4, USP22, and SDHC. Hits can be validated with targeted lipidomics and phenotypic assays.
Imaging and protein interaction assays
Fluorescence microscopy with tagged knock-in lines can visualize localization of enzymes and regulators. Co-immunoprecipitation and proximity labeling can reveal protein complexes involving PPARγ, USP22, or SREBP1. These approaches link molecular interactions to functional changes in fatty acid biosynthesis.
How CRISPR Can Be Used to Study GO:0045723 positive regulation of fatty acid biosynthetic process
Knockout
CRISPR knockout of candidate genes such as ACSL4, USP22, or SDHC can test whether they are required for positive regulation of fatty acid biosynthesis. For example, SDHC deficiency promotes metastasis by reprogramming fatty acid metabolism, and knockout models can reveal loss-of-function phenotypes in lipid accumulation and cancer cell behavior.
Point Mutation
Point mutation knock-in can model disease-associated variants or catalytically dead enzymes. For instance, mutating the deubiquitinase domain of USP22 would test whether its stabilization of PPARγ is enzymatic-activity dependent. Such models provide mechanistic insight beyond simple knockout.
Knock-in
Knock-in of tagged alleles (e.g., GFP or HA) allows visualization and immunoprecipitation of endogenous regulators like SREBP1 or PPARγ. This approach preserves native regulation and can reveal dynamic localization changes during metabolic reprogramming.
Overexpression
Overexpression of genes such as ACSL4 or SREBP1 can drive fatty acid biosynthesis and lipid accumulation, mimicking disease states. In hepatocellular carcinoma, ACSL4 reprograms fatty acid metabolism via c-Myc/SREBP1, and overexpression models can validate sufficiency of a candidate regulator.
How EDITGENE Supports positive regulation of fatty acid biosynthetic process Research
Researchers studying positive regulation of fatty acid biosynthetic process-related genes often need to determine whether a candidate gene is causally involved in lipid metabolic reprogramming. EDITGENE provides a comprehensive suite of CRISPR-based services to enable such causal experiments, from knockout to knock-in and library screening.
Contact EDITGENE today to design your custom CRISPR model for positive regulation of fatty acid biosynthetic process research.
Frequently Asked Questions About positive regulation of fatty acid biosynthetic process
What is GO:0045723?
GO:0045723 is the Gene Ontology term for positive regulation of fatty acid biosynthetic process, defined as any process that activates or increases the frequency, rate or extent of fatty acid formation.
What genes are involved in positive regulation of fatty acid biosynthetic process?
Key genes include SREBP1, ACSL4, PPARγ, USP22, SDHC, TXNIP/VDUP1, SIRT1, PGC-1α, and PPARα, as shown in cancer and steatohepatitis studies.
How is fatty acid biosynthesis positively regulated?
It is regulated transcriptionally by SREBP1 and PPARγ, post-translationally by stabilizing enzymes like USP22, and through signaling pathways such as IL-18/cGAMP and SIRT1/PGC-1α/PPARα.
Why is positive regulation of fatty acid biosynthesis important in cancer?
In cancers such as hepatocellular carcinoma, colorectal cancer, and triple-negative breast cancer, increased fatty acid biosynthesis supports tumor growth and metastasis.
What diseases are linked to GO:0045723?
Diseases include steatohepatitis, hepatocellular carcinoma, colorectal cancer, and triple-negative breast cancer.
How can I study positive regulation of fatty acid biosynthetic process?
Researchers use lipidomics, metabolic flux analysis, RNA-seq, CRISPR screens, and imaging to measure changes in fatty acid biosynthesis and identify regulators.
What is the role of ACSL4 in fatty acid metabolism?
ACSL4 reprograms fatty acid metabolism in hepatocellular carcinoma via c-Myc/SREBP1 and drives TNBC metastasis through histone hyperacetylation.
How does USP22 regulate lipid accumulation?
USP22 stabilizes PPARγ, leading to lipidome accumulation in hepatocellular carcinoma.
What is the connection between SDHC and fatty acid metabolism?
SDHC deficiency promotes metastasis by reprogramming fatty acid metabolism in colorectal cancer.
Can CRISPR be used to study fatty acid biosynthesis?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models enable causal testing of genes involved in positive regulation of fatty acid biosynthesis.
Conclusion
GO:0045723, positive regulation of fatty acid biosynthetic process, is a critical metabolic control point with broad implications for cancer, liver disease, and immune function. The literature highlights SREBP1, ACSL4, PPARγ, USP22, and SDHC as key regulators that reprogram fatty acid metabolism in disease. Understanding these mechanisms requires integrated approaches including CRISPR models, lipidomics, and transcriptomics. EDITGENE provides the tools to dissect this pathway and accelerate therapeutic discovery.
References
- 1. Park HS et al.. 2021. TXNIP/VDUP1 attenuates steatohepatitis via autophagy and fatty acid oxidation.. Autophagy 17(9):2549-2564 PMID: 33190588
- 2. Oteng AB et al.. 2020. Mechanisms of Action of trans Fatty Acids.. Adv Nutr 11(3):697-708 PMID: 31782488
- 3. Liao J et al.. 2024. Formononetin promotes fatty acid β-oxidation to treat non-alcoholic steatohepatitis through SIRT1/PGC-1α/PPARα pathway.. Phytomedicine 124:155285 PMID: 38185065
- 4. Ding Z et al.. 2024. Deficiency of SDHC promotes metastasis by reprogramming fatty acid metabolism in colorectal cancer.. J Transl Med 22(1):544 PMID: 38844980
- 5. Chen J et al.. 2021. ACSL4 reprograms fatty acid metabolism in hepatocellular carcinoma via c-Myc/SREBP1 pathway.. Cancer Lett 502:154-165 PMID: 33340617
- 6. Ning Z et al.. 2022. USP22 regulates lipidome accumulation by stabilizing PPARγ in hepatocellular carcinoma.. Nat Commun 13(1):2187 PMID: 35449157
- 7. Mertens RT et al.. 2024. A metabolic switch orchestrated by IL-18 and the cyclic dinucleotide cGAMP programs intestinal tolerance.. Immunity 57(9):2077-2094.e12 PMID: 38906145
- 8. Sinha A et al.. 2024. ACSL4-mediated H3K9 and H3K27 hyperacetylation upregulates SNAIL to drive TNBC metastasis.. Proc Natl Acad Sci U S A 121(52):e2408049121 PMID: 39700137
