GO:0002023 reduction of food intake in response to dietary excess: Satiety Signaling, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0002023 describes the biological process in which detection of a dietary excess leads to a decrease in nutrient intake, i.e. the physiological brake on eating when calories or specific nutrients are in surplus.
• The process is not a single molecule but an integrated homeostatic circuit: nutrient sensors, gut hormones, adipose-derived signals and hypothalamic and hindbrain neurons converge to suppress feeding.
• Intermittent fasting and continuous energy restriction both engage this process, and the magnitude of the feeding response depends on the macronutrient composition of the excess.
• Hepatic and adipose-derived endocrine factors such as GDF15 and FGF21 are experimentally tractable entry points for manipulating the process in mice.
• Diet composition, including carbohydrate and potassium content, modulates the strength of the compensatory reduction in intake and downstream cardiometabolic outcomes.
• CRISPR knockout, point-mutation, knock-in and overexpression models allow causal testing of candidate genes in this process, and pooled library screening can nominate new regulators.
Description
GO:0002023, reduction of food intake in response to dietary excess, is the Gene Ontology biological process that captures the body's ability to detect a surplus of nutrients and respond by eating less. It is the physiological counterpart of overconsumption: when energy or specific macronutrients exceed requirement, afferent signals from the gut, liver, adipose tissue and circulation act on central feeding circuits to reduce subsequent intake. This process is central to energy balance because a failure to reduce intake in the face of dietary excess is a direct route to obesity, hepatic steatosis and cardiometabolic disease. For researchers, GO:0002023 provides a formal annotation target for experiments that manipulate diet and measure feeding behaviour. Studies of intermittent fasting show that alternating periods of dietary excess and restriction engage adaptive responses that reduce food intake and improve metabolic health. Low-carbohydrate diets illustrate that the macronutrient composition of the excess determines whether the compensatory reduction in intake is sustained or transient. Dietary potassium and sodium studies show that mineral intake also feeds into the same homeostatic logic, linking feeding behaviour to blood-pressure regulation. Because the process is polygenic and environmentally modulated, causal inference requires perturbation. Hepatocyte-specific overexpression of GDF15 improves high-fat-diet-induced obesity and hepatic steatosis in mice via hepatic FGF21 induction, demonstrating that a single engineered genetic change can strengthen the reduction of food intake in response to dietary excess. Randomized trials in metabolic dysfunction-associated steatotic liver disease (MASLD) further show that dietary patterns such as Mediterranean and low-fat diets can resolve steatosis independently of PNPLA3 genotype, indicating that the behavioural output of GO:0002023 is modifiable. This article maps the ontology, mechanism, genes, disease links and experimental methods for GO:0002023.
reduction of food intake in response to dietary excess At A Glance
| GO ID | GO:0002023 |
|---|---|
| GO term | reduction of food intake in response to dietary excess |
| Ontology | biological_process |
| Synonym | none listed in QuickGO |
| Major function | Decrease nutrient intake after detection of a dietary surplus, contributing to energy balance |
| Input signal | Detection of dietary excess, including excess energy or specific macronutrients |
| Output | Reduced food and nutrient intake |
| Key tissues | Hypothalamus and hindbrain feeding circuits, gut, liver and adipose tissue |
| Representative experimental trigger | High-fat or high-carbohydrate feeding followed by intake measurement |
| Disease relevance | Obesity, MASLD, hypertension and gout-related metabolic dysregulation |
What Is GO:0002023?
In plain terms, GO:0002023 is the process by which an organism notices that it has taken in more nutrients than it needs and consequently eats less. The QuickGO definition states that it is an eating behavior process whereby detection of a dietary excess results in a decrease in intake of nutrients. It is therefore an output process: the input is a sensed nutrient surplus, and the measurable output is reduced food or nutrient intake. It should not be confused with satiety after a single meal or with starvation responses; it specifically requires a dietary excess as the trigger.
Why Is reduction of food intake in response to dietary excess Important in Cell Biology?
GO:0002023 matters because the ability to reduce intake when nutrients are in excess is a protective homeostatic response, and its failure is a proximal cause of positive energy balance. Intermittent fasting and energy-restriction paradigms show that engaging this process improves multiple health and disease parameters. Conversely, when the process is blunted, dietary excess is not compensated, favouring obesity, hepatic steatosis and cardiometabolic risk. Because the process integrates diet composition, endocrine signals and central neural circuits, it is a high-value target for mechanistic studies and for therapeutic strategies in metabolic disease.
• Defines the physiological brake that prevents unchecked weight gain during dietary excess.
• Provides a measurable behavioural endpoint for energy-balance research.
• Links macronutrient composition of the diet to subsequent intake and metabolic outcomes.
• Connects feeding behaviour to blood-pressure regulation through mineral intake, notably potassium and sodium.
• Is causally modifiable by single-gene manipulation, as shown for hepatocyte-specific GDF15 overexpression.
• Is relevant to MASLD resolution, where dietary intervention can reverse steatosis regardless of PNPLA3 genotype.
• Intersects with epigenetic and inflammatory mechanisms in gout and related metabolic disease.
• Offers a tractable process for CRISPR knockout, knock-in and overexpression screens in metabolic research.
What Happens During reduction of food intake in response to dietary excess?
Detection of dietary excess
In simple terms: The body first has to notice that too much food or too much of a specific nutrient has been consumed.
The process begins with sensing a nutrient surplus. Dietary excess can be quantitative, as in overfeeding, or qualitative, as in a high-carbohydrate or high-fat load. Nutrient sensors in the gut, liver and adipose tissue respond to the incoming energy and to stored fuel availability, generating afferent signals that report a positive energy state. Intermittent fasting studies show that the timing and duration of the excess period strongly influence the subsequent adaptive response.
Endocrine and neural signal integration
In simple terms: Hormones and nerves carry the 'too much food' message to the brain, where it is integrated.
Once a surplus is detected, circulating factors and vagal afferents converge on hypothalamic and hindbrain circuits that control meal size and frequency. Hepatic endocrine signals are part of this integration: hepatocyte-specific GDF15 overexpression improves high-fat-diet-induced obesity and hepatic steatosis in mice via hepatic FGF21 induction, indicating that liver-derived factors can amplify the response to dietary excess. The integration step determines whether the output is a small adjustment or a sustained reduction in intake.
Suppression of feeding drive
In simple terms: The integrated signal turns down the drive to eat, so the next meal is smaller or delayed.
The behavioural output of GO:0002023 is a decrease in nutrient intake. This is expressed as reduced meal size, reduced meal frequency, or both, depending on the species and the nature of the excess. Low-carbohydrate diets illustrate that the magnitude and durability of this suppression depend on macronutrient composition, with short-term metabolic efficacy sometimes giving way to longer-term limitations. The suppression is not permanent; it persists while the excess signal is present and wanes as energy balance is restored.
Metabolic and epigenetic feedback
In simple terms: Longer-term changes in gene regulation and metabolism tune how strongly the body responds next time.
Repeated or chronic dietary excess engages epigenetic and inflammatory feedback that can modify the strength of the intake reduction. In gout and related metabolic disease, the interaction between epigenetics and food intake influences disease development and severity, showing that the process is embedded in a broader regulatory network. Dietary mineral intake also participates: potassium intake is dose-dependently associated with lower blood pressure in randomized trials, linking the feeding-response system to cardiovascular regulation.
Resolution and clinical translation
In simple terms: If the response works, the excess is corrected and metabolic health improves; if not, disease develops.
Successful engagement of GO:0002023 restores energy balance and can reverse early metabolic pathology. Randomized controlled trials show that Mediterranean and low-fat diets are equally effective in MASLD resolution at 12 weeks regardless of PNPLA3 genotype, demonstrating that behavioural reduction of dietary excess translates into clinical benefit. Non-pharmacological treatment of MASLD similarly relies on sustained reductions in energy intake. These findings position GO:0002023 as a translational endpoint for dietary and genetic interventions.
Key Genes Involved in GO:0002023 reduction of food intake in response to dietary excess
The genes and proteins below are experimentally linked to the detection of dietary excess, the endocrine integration of that signal, or the behavioural reduction of food intake that defines GO:0002023.
| Gene | Major Role | Research Relevance |
|---|---|---|
| GDF15 | Stress and metabolic cytokine that suppresses appetite | Hepatocyte-specific overexpression improves high-fat-diet obesity and steatosis in mice |
| FGF21 | Hepatic hormone that regulates energy balance and feeding | Induced downstream of GDF15 overexpression in liver |
| PNPLA3 | Lipid droplet protein influencing hepatic fat handling | Genotype tested as a modifier of diet-induced MASLD resolution |
| INS | Insulin, a key nutrient-status hormone | Central to postprandial nutrient sensing and energy storage |
| LEP | Leptin, adipose-derived satiety signal | Reports stored energy status to feeding circuits |
| GHRL | Ghrelin, orexigenic gut hormone | Opposes the reduction of intake during dietary excess |
| POMC | Hypothalamic pro-opiomelanocortin precursor | Anorexigenic neuron population in feeding circuits |
| AGRP | Agouti-related peptide, orexigenic neuron marker | Counter-regulates anorexigenic signalling |
| NPY | Neuropeptide Y, orexigenic signal | Modulates feeding drive during energy surplus |
| MC4R | Melanocortin 4 receptor | Central melanocortin pathway controlling meal size |
| GCG | Glucagon and GLP-1 precursor | Gut and pancreatic signal in nutrient handling |
| SLC12A3 | Thiazide-sensitive sodium-chloride cotransporter | Mineral handling relevant to salt-intake reduction strategies |
| CYP27B1 | Vitamin D activation enzyme | Nutrient-responsive metabolic gene in dietary interventions |
| NR1H4 | Farnesoid X receptor, bile acid sensor | Links nutrient excess to hepatic gene regulation |
| PPARA | Peroxisome proliferator-activated receptor alpha | Fatty acid sensor in liver during dietary excess |
| PPARG | Peroxisome proliferator-activated receptor gamma | Adipocyte differentiation and insulin sensitivity |
| ADIPOQ | Adiponectin, insulin-sensitizing adipokine | Adipose-derived signal in energy balance |
| IL1B | Interleukin 1 beta, inflammatory cytokine | Inflammatory link between diet, epigenetics and metabolic disease |
How Is reduction of food intake in response to dietary excess Regulated?
GO:0002023 is regulated at multiple levels. Nutrient-sensing pathways in liver and adipose tissue translate dietary excess into endocrine output, as shown by hepatic GDF15 overexpression inducing FGF21 and improving high-fat-diet-induced obesity and steatosis. Macronutrient composition regulates the strength and durability of the intake reduction, with low-carbohydrate diets showing short-term efficacy but longer-term limitations. Mineral intake provides an additional regulatory layer: potassium intake is dose-dependently associated with lower blood pressure in randomized trials, and salt-intake reduction strategies in hypertensive adults depend on behavioural and environmental enablers. Epigenetic mechanisms interact with food intake to shape the development and severity of metabolic disease such as gout. Finally, dietary intervention trials in MASLD show that the process can be regulated clinically and that host genotype, including PNPLA3, does not abolish the response.
reduction of food intake in response to dietary excess and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| GDF15 | Obesity and hepatic steatosis | Hepatocyte-specific overexpression in high-fat-diet mice |
| FGF21 | Energy balance and steatosis | Knockout and knock-in models in diet-induced obesity |
| PNPLA3 | MASLD and lipid handling | Point-mutation knock-in of risk variant with dietary challenge |
| IL1B | Gout and diet-related inflammation | Knockout in dietary-excess and inflammation models |
| SLC12A3 | Hypertension and salt handling | Knockout and point-mutation models with dietary sodium challenge |
Obesity and hepatic steatosis
Failure to reduce food intake in response to dietary excess promotes positive energy balance, obesity and hepatic steatosis. In mice, hepatocyte-specific GDF15 overexpression improves high-fat-diet-induced obesity and hepatic steatosis via hepatic FGF21 induction, directly linking a genetic manipulation of this process to disease improvement. Intermittent fasting paradigms that repeatedly engage the process improve multiple health and disease parameters.
MASLD and metabolic liver disease
Metabolic dysfunction-associated steatotic liver disease is strongly influenced by dietary excess and by the compensatory reduction in intake. A randomized controlled trial showed that Mediterranean and low-fat diets are equally effective in MASLD resolution at 12 weeks regardless of PNPLA3 genotype. Non-pharmacological treatment of MASLD relies on sustained behavioural reduction of energy intake, reinforcing the clinical importance of GO:0002023.
Hypertension and mineral-related metabolic disease
The feeding-response system also governs mineral intake, which has cardiovascular consequences. Potassium intake is dose-dependently associated with lower blood pressure in a meta-analysis of randomized controlled trials. Barriers and enablers to salt-intake reduction in adults with high blood pressure show that behavioural factors determine whether the reduction in intake is achieved. These findings connect GO:0002023 to hypertension management.
Gout and inflammation
Dietary excess interacts with epigenetic regulation in the development and severity of gout. The interaction between epigenetics and food intake shapes inflammatory and metabolic pathways relevant to gout and offers therapeutic perspectives. This illustrates that GO:0002023 is not only a metabolic process but also a modifier of inflammatory disease.
From reduction of food intake in response to dietary excess-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is a candidate gene required for the reduction of intake after dietary excess? | CRISPR knockout in mice or cell models with feeding or nutrient-sensing readouts |
| Does a specific human variant alter the response to dietary excess? | Point-mutation knock-in of the variant followed by dietary challenge |
| Can a protective allele enhance the reduction of intake? | Knock-in of the protective allele with metabolic phenotyping |
| Where and when is the gene product expressed during dietary excess? | Tagged knock-in with imaging and biochemical tracing |
| Does increasing gene dosage strengthen the response? | Overexpression, for example hepatocyte-specific GDF15 overexpression |
| Which new genes regulate the process? | Pooled CRISPR library screening under dietary-excess conditions |
How to Study the reduction of food intake in response to dietary excess Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Food intake monitoring | Amount and timing of nutrient intake | Quantifying the reduction of intake after dietary excess |
| Metabolic cage phenotyping | Energy expenditure, intake and substrate use | Integrated energy-balance assessment |
| Hormone immunoassays | Circulating GDF15, FGF21, leptin, insulin | Linking endocrine signals to feeding behaviour |
| RNA sequencing | Transcriptional changes in liver and brain | Nominating regulators of the response |
| Epigenetic profiling | DNA methylation and chromatin state | Diet-gene interaction in metabolic disease |
| Randomized dietary trial | Clinical resolution of metabolic disease | Testing dietary strategies in MASLD |
| Blood-pressure monitoring | Cardiovascular response to mineral intake | Potassium and sodium intervention studies |
| CRISPR library screening | Fitness of gene knockouts under dietary excess | Discovery of new regulators |
Feeding behaviour and intake measurement
The defining output of GO:0002023 is reduced nutrient intake, so direct measurement of food intake, meal size and meal frequency is the primary assay. Intermittent fasting and energy-restriction protocols provide standardized dietary-excess and restriction phases for quantifying the response. Macronutrient-controlled diets allow separation of energy excess from specific nutrient excess.
Endocrine and metabolic profiling
Circulating hormones and metabolites report the internal state that drives the behavioural output. Hepatic GDF15 and FGF21 can be measured in overexpression and knockout models to link molecular changes to intake reduction. Insulin, leptin and related analytes provide context for energy-balance interpretation.
Transcriptomic and epigenetic analysis
RNA sequencing and epigenetic assays identify the gene-regulatory changes that accompany or cause the response. Epigenetic mechanisms interact with food intake in metabolic disease such as gout, making chromatin and methylation profiling informative. Transcriptional profiling of liver and hypothalamus after dietary excess reveals candidate regulators for functional follow-up.
Clinical and dietary intervention studies
Randomized controlled trials test whether dietary strategies that engage GO:0002023 produce clinical benefit. Mediterranean and low-fat diets were compared for MASLD resolution at 12 weeks with genotype stratification. Non-pharmacological MASLD treatment and salt-reduction studies provide templates for behavioural and cardiovascular endpoints.
How CRISPR Can Be Used to Study GO:0002023 reduction of food intake in response to dietary excess
Knockout
CRISPR knockout is used to test whether a candidate gene is required for the reduction of food intake in response to dietary excess. Deleting a gene such as Gdf15 or Fgf21 in mice or in metabolically relevant cell models, followed by dietary challenge and intake measurement, can establish necessity. Knockout screens in pooled format extend this to hundreds of genes simultaneously.
Point Mutation
Point-mutation models introduce specific human variants to test whether a single nucleotide change alters the response to dietary excess. This is particularly relevant for genes such as PNPLA3, where genotype was examined as a modifier of diet-induced MASLD resolution. Precise base editing or homology-directed repair allows isogenic comparison of variant and wild-type alleles.
Knock-in
Knock-in models place a reporter, tag or protective allele at an endogenous locus to study expression and function during dietary excess. Tagged knock-in enables imaging and biochemical tracing of the gene product in liver or brain. Knock-in of protective alleles can test whether enhancing the process improves metabolic outcomes.
Overexpression
Overexpression tests sufficiency: does increasing gene dosage strengthen the reduction of food intake after dietary excess? Hepatocyte-specific GDF15 overexpression improves high-fat-diet-induced obesity and hepatic steatosis in mice via hepatic FGF21 induction, providing a direct example of this strategy. Tissue-specific promoters allow the contribution of liver, adipose tissue or brain to be dissected.
How EDITGENE Supports reduction of food intake in response to dietary excess Research
Researchers studying reduction of food intake in response to dietary excess-related genes often need to determine whether a candidate gene is causally involved in sensing nutrient surplus, integrating endocrine signals, or suppressing feeding drive. Observational associations and transcriptomic correlations cannot establish causality, so engineered cell and animal models are required. EDITGENE provides the full pipeline from guide design to validated clonal lines and pooled screens, enabling rigorous testing of GO:0002023-related hypotheses.
Contact EDITGENE today to design your custom CRISPR model for reduction of food intake in response to dietary excess research.
Frequently Asked Questions About reduction of food intake in response to dietary excess
What is GO:0002023 reduction of food intake in response to dietary excess?
It is a Gene Ontology biological process in which detection of a dietary excess results in a decrease in nutrient intake, acting as a homeostatic brake on overconsumption.
What genes are involved in reduction of food intake in response to dietary excess?
Key genes include GDF15 and FGF21 in liver endocrine signalling, PNPLA3 in hepatic lipid handling, and central feeding genes such as POMC, AGRP, NPY and MC4R.
How is reduction of food intake in response to dietary excess measured?
It is measured by monitoring food intake, meal size and meal frequency during and after a controlled dietary-excess period, often combined with hormone and metabolic profiling.
Why is reduction of food intake in response to dietary excess important for obesity research?
Because failure of this process allows dietary excess to go uncompensated, promoting positive energy balance, obesity and hepatic steatosis.
Does intermittent fasting engage reduction of food intake in response to dietary excess?
Yes, intermittent fasting alternates dietary excess and restriction phases and engages adaptive responses that reduce intake and improve health parameters.
Does diet composition affect reduction of food intake in response to dietary excess?
Yes, macronutrient composition matters; low-carbohydrate diets show short-term metabolic efficacy but longer-term limitations, indicating that the response is diet-dependent.
Can CRISPR models be used to study reduction of food intake in response to dietary excess?
Yes, knockout, point-mutation, knock-in and overexpression models allow causal testing, as illustrated by hepatocyte-specific GDF15 overexpression in mice.
Is reduction of food intake in response to dietary excess linked to MASLD?
Yes, dietary interventions that reduce energy intake can resolve MASLD, and Mediterranean and low-fat diets were equally effective at 12 weeks regardless of PNPLA3 genotype.
How does mineral intake relate to reduction of food intake in response to dietary excess?
Mineral intake is part of the feeding response; potassium intake is dose-dependently associated with lower blood pressure, and salt-reduction strategies depend on behavioural enablers.
What experimental models are best for studying reduction of food intake in response to dietary excess?
Diet-induced obesity mouse models with genetic perturbation, isogenic cell lines for variant testing, and randomized dietary trials for clinical translation are commonly used.
Conclusion
GO:0002023, reduction of food intake in response to dietary excess, is a central homeostatic process that converts nutrient surplus detection into reduced eating. Its molecular logic spans gut, liver, adipose and central feeding circuits, with GDF15 and FGF21 providing experimentally validated entry points. Dietary composition and mineral intake modulate the strength of the response, and clinical trials show that engaging the process can resolve metabolic disease such as MASLD. Because the process is polygenic and environmentally sensitive, causal inference depends on precise genetic perturbation. CRISPR knockout, point-mutation, knock-in, overexpression and pooled library screening provide the toolkit needed to identify and validate regulators of GO:0002023, and EDITGENE offers end-to-end support for these studies.
References
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- 2. Barber TM et al.. 2021. The Low-Carbohydrate Diet: Short-Term Metabolic Efficacy Versus Longer-Term Limitations.. Nutrients 13(4) PMID: 33916669
- 3. Filippini T et al.. 2020. Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials.. J Am Heart Assoc 9(12):e015719 PMID: 32500831
- 4. Takeuchi K et al.. 2024. Hepatocyte-specific GDF15 overexpression improves high-fat diet-induced obesity and hepatic steatosis in mice via hepatic FGF21 induction.. Sci Rep 14(1):23993 PMID: 39402176
- 5. Dogay Us G et al.. 2025. Mediterranean and low-fat diets are equally effective in MASLD resolution at 12 weeks regardless of PNPLA3 genotype: A randomized controlled trial.. Hepatol Commun 9(12) PMID: 41284948
- 6. Georgel PT et al.. 2021. Where Epigenetics Meets Food Intake: Their Interaction in the Development/Severity of Gout and Therapeutic Perspectives.. Front Immunol 12:752359 PMID: 34603340
- 7. Khalesi S et al.. 2024. Barriers and enablers to salt intake reduction in Australian adults with high blood pressure.. Br J Nutr 132(6):815-822 PMID: 39376125
- 8. Dufour JF et al.. 2026. Non-pharmacological treatment of MASLD.. Diabetologia PMID: 42502137
