Energy Intake

Energy intake refers to the total amount of energy consumed through food and beverages, typically measured in calories or joules. It is a fundamental physiological process vital for sustaining life, providing the necessary fuel for all bodily functions, growth, and physical activity. Maintaining a balance between energy intake and energy expenditure is crucial for overall health and weight management.

Biological Basis

The regulation of energy intake is a complex biological process controlled by an intricate network of hormones, neurotransmitters, and neural circuits that govern hunger, satiety, and food-seeking behaviors. Key brain regions, such as the hypothalamus, integrate signals from the gastrointestinal tract, adipose tissue, and other organs to maintain energy homeostasis. Genetic factors are known to influence individual differences in appetite, food preferences, and metabolic responses, thereby contributing to variations in energy intake. For instance, studies have identified specific genetic variants associated with aspects of energy intake. An intronic variant inTMEM229Bon chromosome 14 has been associated with ad libitum energy intake at dinner.^[1] Furthermore, a coding variant (rs8040868 ) in acetylcholine receptors, which activate proopiomelanocortin neurons and melanocortin-4 receptors, has been suggested to play a role in the regulation of energy intake and expenditure.^[1]

Clinical Relevance

Imbalances in energy intake relative to energy expenditure are a primary driver of weight changes. Chronic excess energy intake can lead to an energy surplus, resulting in overweight and obesity. These conditions are associated with a wide range of health problems, including type 2 diabetes, cardiovascular diseases, certain cancers, and musculoskeletal disorders. Conversely, insufficient energy intake can lead to malnutrition, unintended weight loss, and impaired physiological function. Understanding the factors that influence energy intake is critical for developing effective strategies to prevent and manage these significant public health challenges.

Social Importance

Energy intake also carries significant social implications, influencing public health policies, food systems, and individual lifestyle choices. Societal factors such as food availability, cultural eating practices, socioeconomic status, and marketing strategies all interact with biological predispositions to shape dietary patterns and overall energy consumption. Addressing issues related to energy intake requires a multifaceted approach that considers individual biological variations, environmental influences, and broader societal contexts.

Methodological and Statistical Constraints

Genome-wide association studies (GWAS) encounter significant methodological and statistical hurdles that can affect the reliability and interpretation of their findings. A primary concern is the statistical power, which is often inadequate to detect genetic variants with small effect sizes, especially when rigorous genome-wide significance thresholds (e.g., p < 5.0 × 10^-8) are employed to adjust for the extensive multiple testing across the genome.^[2] Consequently, numerous true associations, particularly involving less-frequent variants, may remain undiscovered without the use of exceptionally large sample sizes, often exceeding 35,000 individuals.^[3] Moreover, the effect sizes reported in initial discovery studies are susceptible to inflation due to the “winner’s curse” phenomenon, which can lead to overestimations of a variant’s true impact and subsequently misguide power calculations for replication efforts.^[2] The challenge of distinguishing genuine genetic signals from random statistical noise is compounded by the immense number of comparisons performed in GWAS. While strategies such as Bonferroni correction or weighted p-value procedures are designed to manage the false positive rate, the specific weighting function chosen can alter the ranking of hypotheses and the ultimate number of significant associations identified.^[2] This inherent complexity underscores the critical need for robust replication across independent cohorts to validate initial findings and mitigate the risk of reporting spurious associations. The observation of replication gaps, where nominally significant SNPs fail to reach genome-wide significance in subsequent studies, highlights the persistent difficulty in consistently identifying true positive genetic effects amidst high-throughput data.^[2]

Phenotype and Environmental Confounding

The accuracy and consistency of phenotype are crucial, yet various methods can introduce variability and bias into genetic association studies. For instance, relying on self-reported data can be influenced by demographic characteristics such as age and sex, or by daily responsibilities like childcare, potentially leading to skewed estimates of the trait.^[4] Furthermore, disparate approaches across different study cohorts, such as calculating a trait from multiple self-reported components versus direct reporting in broad categories, can produce correlated but distinct estimates, thereby impacting the transferability and comparability of genetic findings across studies.^[4] Environmental factors and population substructure further complicate the precise identification of genetic associations. Factors like irregular work schedules or shared household and block units can introduce environmental correlations that confound genetic signals if not adequately addressed in statistical models.^[4] Population stratification, where systematic differences in allele frequencies align with phenotypic differences due to distinct ancestral backgrounds, can result in spurious associations if not meticulously controlled through methods such as incorporating quantitative ancestry indices as covariates.^[5] Although advanced quality control measures and adjustments for population structure are routinely implemented, their efficacy can vary, and residual confounding may still persist.^[6]

Generalizability and Remaining Knowledge Gaps

The ability to generalize genetic findings is often constrained by the specific demographic and ancestral characteristics of the study cohorts. Variations in age, sex distribution, and lifestyle factors, such as the prevalence of shift work among participants, can influence the observed genetic effects and limit their broader applicability.^[4] Furthermore, if studies primarily focus on populations of European ancestry, the identified genetic variants may not fully represent the genetic architecture of traits in other ancestral groups, underscoring the necessity for more diverse cohorts to enhance the global relevance of findings.^[6] Despite substantial advances, a considerable proportion of the heritability for complex traits frequently remains unexplained by the common genetic variants currently identified, a phenomenon often referred to as “missing heritability.” This persistent gap suggests that a significant number of genetic influences may stem from rare variants, structural variations, intricate gene-gene interactions, or complex gene-environment interactions that are not comprehensively captured by current GWAS methodologies.^[4] Acknowledging these outstanding knowledge gaps is essential for directing future research towards more comprehensive genomic analyses and fostering a deeper understanding of the intricate interplay between genetic and environmental factors in shaping human traits.

Variants

Genetic variations play a crucial role in shaping an individual’s energy intake, metabolism, and susceptibility to various metabolic conditions. Among these, variants in genes likeFGF21 and IZUMO1 have been specifically linked to dietary preferences. FGF21(Fibroblast Growth Factor 21) is a hormone that acts as a key regulator of energy metabolism, influencing glucose and lipid homeostasis, and is known to modulate appetite and sweet taste perception. The A allele ofrs838133 within FGF21 has been associated with a higher intake of total sugars, highlighting its impact on dietary choices.^[7] Similarly, the G allele of rs838145 , located near the IZUMO1 gene, also shows an association with increased total sugar intake, suggesting that this genomic region influences food preferences.^[7] While IZUMO1 is primarily recognized for its role in fertilization, related variants like rs838147 may indirectly impact metabolic pathways or neural circuits that control food intake.

Other significant genetic factors influencing energy balance include variants in FTO and ALDH2. The FTOgene, or Fat Mass and Obesity-associated protein, is a prominent genetic determinant of body weight and composition, largely by modulating appetite and satiety signals within the brain.^[8] The rs1421085 variant in FTOis a well-established risk factor for obesity, linked to increased food intake and altered responses to hunger cues, likely by influencingFTO expression in relevant brain regions.^[8] In contrast, ALDH2 (Aldehyde Dehydrogenase 2) is crucial for detoxifying acetaldehyde, a byproduct of alcohol metabolism. The rs671 variant in ALDH2 significantly reduces the enzyme’s activity, leading to acetaldehyde accumulation that causes unpleasant physical reactions, thereby influencing alcohol consumption and, consequently, caloric intake derived from alcohol.^[7] Beyond these, genes such as RARB, NAA25, and TRAFD1also contribute to the complex interplay of genetics and energy intake. TheRARBgene encodes Retinoic Acid Receptor Beta, a nuclear receptor vital for cell growth, differentiation, and metabolic regulation, mediating the effects of vitamin A derivatives.^[8] Variants like rs7619139 in RARBmay subtly influence lipid and glucose metabolism, impacting how the body processes nutrients and maintains energy balance.^[8] The NAA25 gene, encoding N-alpha-acetyltransferase 25, is involved in N-terminal acetylation, a fundamental protein modification that affects protein stability and function across numerous cellular and metabolic processes, with rs11066132 potentially altering these functions. Furthermore, TRAFD1 (TRAF-type zinc finger domain containing 1) is implicated in immune and inflammatory responses, and given the link between chronic low-grade inflammation and metabolic dysfunction, a variant like rs12231737 could influence energy homeostasis and body weight.^[7] Non-coding RNAs and genes involved in neural development also play roles in energy regulation. The intergenic region containing the RN7SL423P pseudogene and TANK-AS1, a long non-coding RNA (lncRNA), includes the variant rs197273 . These non-coding elements can regulate the expression of nearby genes involved in immune responses and metabolism, thereby affecting overall energy expenditure and nutrient sensing.^[8] Similarly, LINC02775, another lncRNA, with its variant rs1440620 , may exert regulatory control over metabolic pathways, although its precise mechanisms related to energy intake are still under investigation.^[7] Lastly, TENM2 (Teneurin Transmembrane Protein 2), a gene essential for neuronal development and synapse formation, has the variant rs1549309 that may influence neural circuits governing appetite, satiety, and food preferences, thus impacting an individual’s total energy intake.

Key Variants

RS ID	Gene	Related Traits
rs671	ALDH2	body mass index erythrocyte volume mean corpuscular hemoglobin concentration mean corpuscular hemoglobin coronary artery disease
rs11066132	NAA25	body weight epilepsy fish consumption angina pectoris colorectal cancer
rs12231737	TRAFD1	cups of coffee per day hypertension blood urea nitrogen amount carbohydrate intake coffee consumption
rs838133	FGF21	homocysteine energy intake cathepsin D triglyceride taste liking
rs7619139	RARB	body mass index physical activity , body mass index sodium energy intake taste liking
rs1421085	FTO	body mass index obesity energy intake pulse pressure lean body mass
rs838145 rs838147	IZUMO1	energy intake alcohol consumption quality taste liking erythrocyte volume total cholesterol
rs197273	RN7SL423P - TANK-AS1	alcohol consumption quality energy intake Alzheimer disease, polygenic risk score
rs1440620	LINC02775	energy intake
rs1549309	TENM2	energy intake

Definition and Core Concepts of Energy Intake

Energy intake refers to the total caloric content derived from all food and beverages consumed by an individual. It serves as a primary input in the body’s energy balance equation, which dictates whether an individual gains, loses, or maintains weight when compared against energy expenditure. The conceptual framework often positions the “central control of energy balance” as a complex, heritable system whose dysregulation can contribute to conditions like obesity.^[9]A sustained “energy imbalance,” where energy intake consistently exceeds the body’s energy expenditure, is a fundamental mechanism underlying the development of weight gain and, specifically, childhood obesity.^[10]Related terminology includes “total dietary energy intake,” which is a precise term used in research to quantify daily caloric consumption.^[11] The behavioral aspect of consumption is captured by concepts such as “hyperphagic eating behavior,” which describes an excessive drive to eat and is associated with appetite-related hormones.^[12]Furthermore, the “consumption of sweet substances” represents a specific component of overall energy intake that can be studied for its perceptual and genetic influences.^[13]

and Operationalization

The operational definition of energy intake involves the quantitative assessment of caloric value from dietary sources, typically expressed in kilocalories per day (kcal/day).^[11] In research, various approaches are employed to estimate this value, with the “multiple-pass 24-hour recall” being a common method for obtaining detailed dietary information.^[14]The accuracy of these self-reported intake estimates is a critical consideration, and they are often compared against objective measures of total energy expenditure, such as those determined by the “doubly labeled water method,” to assess their validity and reliability.^[14]For statistical analysis, raw energy intake data may require transformations, such as “log transformation,” to ensure compliance with model assumptions.^[11]These criteria are essential for establishing the relationship between dietary patterns and various health markers. For instance, studies frequently investigate the association between measured “diet composition” and “body mass index” (BMI) in different populations.^[15]Precise and reliable of energy intake is thus foundational for both clinical assessments and large-scale genetic and environmental studies investigating metabolic health.^[16]

Classification and Clinical Significance

While “energy intake” itself is a physiological process, its quantitative state—whether in deficit, balance, or surplus—is directly classified in relation to metabolic health outcomes. A chronic positive “energy imbalance,” characterized by energy intake exceeding expenditure, is the fundamental pathophysiological mechanism leading to the development of overweight and obesity.^[10]These conditions are formally classified based on severity using metrics such as Body Mass Index (BMI).^[17]highlighting the clinical significance of intake levels. Research endeavors aim to identify “pathways that control energy intake and expenditure in obesity”.^[18] suggesting that disruptions in these regulatory systems can be sub-classified based on their genetic or physiological underpinnings.

Understanding the dynamics of energy intake is paramount in elucidating the “pathophysiology of childhood obesity”.^[1] where early life dietary patterns and behaviors significantly influence long-term health. The study of “hyperphagic eating behavior”.^[12]for example, offers insights into specific behavioral subtypes related to excessive intake. Ultimately, detailed classification and of energy intake are crucial for developing targeted interventions and for advancing the understanding of metabolic disorders.

Systemic Regulation of Energy Homeostasis

Energy intake is tightly controlled by complex physiological systems that maintain energy homeostasis within the human body. This balance is achieved through intricate interactions between humoral (hormonal) and neural mechanisms that regulate glucose absorption, production, and utilization.^[19] For instance, the brain plays a critical role in perceiving and integrating signals related to energy balance.^[20] Specific neural pathways, such as the activation of Pro-Opiomelanocortin (POMC) neurons by compounds like nicotine, can influence food intake, demonstrating the direct neural control over energy intake behaviors.^[21]Hormonal signals, often referred to as humoral mechanisms, are essential for communicating energy status across different organ systems. Hormones like insulin are crucial for regulating glucose utilization by various insulin-sensitive and insulin-insensitive tissues, thereby influencing systemic energy availability.^[19]Furthermore, biomolecules such as 1,25-dihydroxyvitamin D3 exert broad regulatory effects, targeting cells in diverse organs including the intestinal tract, stomach, kidney, skin, pituitary, and parathyroid, suggesting a widespread influence on metabolic processes that can indirectly affect energy intake and utilization.^[22]

Cellular Metabolism and Bioenergetic Pathways

At the cellular level, energy intake culminates in intricate metabolic processes that convert nutrients into usable energy. Glucose stands as the primary energy source for human cells, and its levels are meticulously controlled through a balance of absorption from the gut, production predominantly by the liver, and utilization by various tissues.^[19]Key enzymes, such as glucokinase, are central to glucose metabolism, acting as a crucial regulator in glucose phosphorylation within cells and thus impacting the overall cellular energy landscape.^[23] Cellular energy status is also sensed and regulated by critical proteins like AMP-activated protein kinase (AMPK). Mutations in subunits like the gamma.^[24] subunit of AMPKcan lead to severe pathophysiological conditions, such as familial hypertrophic cardiomyopathy, by causing an energy compromise within the affected cells.^[25] This highlights AMPK’s vital role in maintaining cellular energy balance and preventing disease. The precise molecular mechanisms involving glucokinase andAMPK underscore the intricate regulatory networks governing cellular energy metabolism, ensuring that energy supply meets demand.

Genetic and Epigenetic Regulation of Energy Traits

Genetic mechanisms play a fundamental role in shaping an individual’s energy intake and overall energy balance. Genetic approaches are essential for understanding the perception and integration of energy signals within the body.^[20] Gene expression patterns in specific tissues, such as global gene expression profiling in pancreatic islets, reveal the molecular responses to metabolic challenges and the potential for therapeutic interventions like Glp-1 gene therapy to influence energy metabolism.^[26] Beyond direct gene function, epigenetic modifications also contribute significantly to the regulation of energy traits. The BORIS and CTCF gene family, for example, is uniquely involved in the epigenetics of normal biology, suggesting that modifications to gene expression without altering the underlying DNA sequence can impact metabolic regulation.^[27]Such epigenetic factors, alongside specific genetic predispositions, are implicated in conditions like Prader-Willi syndrome, which is characterized by severe disruptions in appetite and energy intake.^[28]Furthermore, regulatory elements within genes, like the vitamin D response element of theinvolucrin gene, demonstrate how specific biomolecules such as 1,25-dihydroxyvitamin D3 can mediate gene regulation, highlighting a complex interplay between genetic programming and environmental signals.^[24]

Organ System Interactions and Pathophysiology of Energy Dysregulation

The regulation of energy intake is a systemic process involving integrated functions across multiple organs and tissues. The gastrointestinal tract is responsible for nutrient absorption, while the liver plays a primary role in glucose production, and various insulin-sensitive and insulin-insensitive tissues are critical for glucose utilization.^[19]Disruptions in these organ-specific functions can lead to systemic homeostatic imbalances; for instance, damage to pancreatic beta-cells, which are responsible for insulin production, can profoundly impact glucose metabolism and overall energy regulation.^[26]Pathophysiological processes arise when these finely tuned systems are disrupted, leading to conditions that profoundly affect energy intake and balance. Genetic disorders like Prader-Willi syndrome exemplify severe homeostatic disruption, characterized by an insatiable appetite and subsequent obesity due to central nervous system dysfunction affecting satiety.^[28] Similarly, compromised energy metabolism at the cellular level, such as that caused by mutations in the AMPK gamma.^[24]subunit, can lead to severe organ-specific diseases like familial hypertrophic cardiomyopathy, underscoring the critical link between cellular bioenergetics and systemic health.^[25] These examples illustrate how failures in molecular pathways and tissue interactions contribute to chronic diseases related to energy dysregulation.

Neurohumoral Regulation of Energy Intake

The regulation of energy intake is a complex process orchestrated by intricate neurohumoral signaling pathways that integrate peripheral metabolic cues with central nervous system responses. Receptors in various tissues detect circulating hormones and nutrients, triggering intracellular signaling cascades that modulate neuronal activity and gene expression. For instance, pro-opiomelanocortin (POMC) neurons in the hypothalamus play a critical role in satiety, with their activation leading to decreased food intake.^[21]This perception and integration of energy balance signals involve extensive network interactions and feedback loops, ensuring a tightly controlled balance between nutrient availability and energy expenditure.

This sophisticated system relies on both humoral mechanisms, involving hormones like insulin and leptin, and neural mechanisms, including projections from the pontomesencephalic tegmentum to various brain regions involved in appetite and reward.^[21]These pathways engage in significant crosstalk, where signals from one pathway can influence or modify the activity of another, contributing to a robust hierarchical regulation of energy intake. The functional significance of this integrated control is to maintain metabolic homeostasis, adapting to varying energy demands and nutrient availability to prevent conditions of energy deficit or excess.

Metabolic Orchestration of Nutrient Utilization

Energy intake is intrinsically linked to metabolic pathways that govern the absorption, production, and utilization of major energy sources. Glucose, as a primary energy currency, is absorbed via the gut, produced predominantly by the liver through gluconeogenesis and glycogenolysis, and utilized by both insulin-sensitive and insulin-insensitive tissues. Enzymes like glucokinase (GCK) are central to glucose phosphorylation, acting as a crucial regulator of glucose metabolism in the liver and pancreatic beta cells.^[23]The activity and regulation of such enzymes are critical for controlling metabolic flux, ensuring that glucose levels are maintained within a narrow homeostatic range.

Beyond glucose, other macromolecules like fats and proteins are also processed through catabolic pathways to generate ATP or directed into anabolic pathways for biosynthesis and storage. Metabolic regulation is achieved through various mechanisms, including allosteric control of key enzymes, covalent modifications like phosphorylation, and transcriptional regulation of metabolic enzyme genes. These regulatory mechanisms allow cells to rapidly adjust their metabolic output in response to changes in energy status or nutrient availability, dynamically balancing energy production and consumption.

Genetic and Epigenetic Influences on Energy Balance

Genetic and epigenetic mechanisms fundamentally underpin the efficiency and responsiveness of energy balance systems, influencing individual predispositions to variations in energy intake and metabolic phenotypes. Gene regulation, including transcriptional control and post-translational modifications, dictates the expression and activity of proteins involved in nutrient sensing, metabolism, and signaling. Genetic approaches have been instrumental in studying energy balance, revealing that variations in specific genomic regions can be associated with metabolic traits.^[20] For example, variations within the G6PC2/ABCB11genomic region have been linked to fasting glucose levels, highlighting the genetic basis of glucose homeostasis.

Beyond stable genetic variations, epigenetic modifications such as DNA methylation and histone acetylation can alter gene expression without changing the underlying DNA sequence, providing another layer of regulatory control over energy intake pathways. These modifications can be influenced by environmental factors, including diet, and can lead to long-term changes in metabolic programming. The intricate interplay between genetic predispositions and epigenetic adaptations contributes to the diverse individual responses to dietary intake and the overall regulation of energy balance.

Pathophysiological Mechanisms and Therapeutic Insights

Dysregulation within the complex pathways governing energy intake and metabolism can lead to significant health consequences, including obesity, type 2 diabetes, and other metabolic disorders. When feedback loops fail or signaling cascades are disrupted, the delicate balance between energy intake and expenditure is compromised. For instance, mutations in the gamma.^[24] subunit of AMPK(AMP-activated protein kinase) can cause familial hypertrophic cardiomyopathy, providing evidence for the central role of energy compromise in disease pathogenesis.^[25]Such pathway dysregulation can trigger compensatory mechanisms, but these are often insufficient to restore full homeostasis in the long term, leading to chronic disease states.

Understanding these disease-relevant mechanisms is crucial for identifying potential therapeutic targets. By pinpointing specific components within signaling pathways, metabolic enzymes, or regulatory genes that are perturbed in disease, researchers can develop interventions aimed at restoring proper function. Modulating receptor activation, inhibiting or activating specific enzymes, or correcting gene expression through genetic or pharmacological approaches represent avenues for therapeutic development. The insights gained from studying these pathways offer promising strategies for managing and treating conditions related to aberrant energy intake.

Clinical Relevance

The concept of energy intake holds significant clinical relevance, influencing a wide spectrum of physiological processes, disease risk, and patient management strategies. Understanding an individual’s energy consumption patterns is crucial for assessing health status, predicting disease trajectories, and tailoring therapeutic interventions.

Prognostic and Risk Stratification for Cardiometabolic Disease

Energy intake, particularly its macronutrient composition, profoundly influences an individual’s susceptibility to and progression of cardiometabolic diseases. Studies have demonstrated clear associations between dietary macronutrient intake and plasma lipid profiles, providing valuable insights for assessing cardiovascular risk.^[29] For instance, specific fatty acid compositions in plasma and erythrocyte membranes, which reflect dietary intake, have been linked to the risk of new-onset type 2 diabetes (T2D).^[30]Furthermore, alcohol intake, a significant source of dietary energy, is associated with the risk of coronary heart disease (CHD) across various adult age groups.^[31] These findings enable clinicians to stratify patient risk more effectively, identifying individuals at higher risk for T2D and CHD, and guiding personalized preventive and management strategies to improve long-term outcomes.

Energy Intake and Body Weight Regulation

Energy intake is a primary determinant of body weight and body mass index (BMI), which are critical prognostic factors for numerous chronic health conditions. Variations in total energy consumption, alongside the overall composition of the diet, are strongly associated with BMI.^[15]Research has identified protein-altering genetic variants linked to BMI that implicate pathways controlling both energy intake and expenditure, underscoring a genetic component to individual differences in obesity risk.^[18]Understanding these interactions is essential for identifying high-risk individuals and developing personalized interventions for weight management, considering both lifestyle and genetic predispositions.

Clinical Assessment and Monitoring Strategies

Accurate and monitoring of energy intake are foundational clinical applications for diagnostic evaluation and ongoing patient care. Validated methodologies, such as food frequency questionnaires (FFQs), are widely utilized to quantify dietary intake, exhibiting good reproducibility and accuracy across diverse patient populations.^[32] These tools are indispensable for tracking population-level trends in energy and macronutrient consumption, which have shown dynamic changes over recent decades.^[33] Additionally, objective measures such as the fatty acid composition of adipose tissue and blood serve as valuable biomarkers of dietary intake, complementing self-reported data to enhance the precision of nutritional assessments and guide tailored therapeutic interventions.^[34]

Frequently Asked Questions About Energy Intake

These questions address the most important and specific aspects of energy intake based on current genetic research.

---

1. Why can’t I lose weight even when my friend eats more than me?

Your body’s energy intake is influenced by a complex interplay of genetic factors that affect your appetite, food preferences, and how your metabolism responds to food. Even if you eat the same amount, individual genetic differences can mean your body processes and stores energy differently. For example, variants in genes likeTMEM229B or those related to acetylcholine receptors can subtly influence how much you feel like eating and how your body uses that energy.

2. My sibling is thin but I’m not - why the difference?

Even among siblings, there are unique genetic variations that influence how each person’s body regulates energy intake and expenditure. While you share many genes, specific genetic variants can lead to different appetites, metabolic rates, and responses to food. For instance, differences in genes affecting satiety signals or fat storage can mean one sibling naturally consumes less or burns more energy than another.

3. Why do some people never gain weight no matter what they eat?

Some individuals have genetic predispositions that give them a more efficient metabolism or stronger satiety signals, making it harder for them to accumulate excess energy. Their bodies might naturally burn more calories at rest or have genetic variants that influence how much food they crave or how quickly they feel full. This can involve genes that regulate hormones and neurotransmitters controlling hunger and satiety.

4. Does my ancestry affect my weight?

Yes, your ancestral background can play a role because genetic variations linked to energy intake and weight often differ across populations. For example, specific genetic variants identified in one ethnic group, like those studied in the Hispanic population, might not be as prevalent or have the same effect in others. This highlights the importance of diverse research to understand how genetics influence weight across different ancestries.

5. Can I really overcome my family’s tendency to gain weight?

While genetics certainly influence your predisposition to weight gain, they are not your sole destiny. Lifestyle choices like diet and exercise interact significantly with your genetic makeup. Even if you have genetic variants that increase your risk, consistent healthy habits can often mitigate these effects and help you manage your weight effectively.

6. Does what I eat for dinner matter more than other meals for my weight?

Interestingly, some research suggests that genetic factors can specifically influence energy intake at certain meals. For example, an intronic variant in theTMEM229B gene has been associated with how much energy a person consumes at dinner. This means your genetic makeup might make you more prone to overeating during your evening meal, potentially impacting overall energy balance.

7. Why do I always feel hungry, even after a big meal?

Your feelings of hunger and fullness are regulated by a complex network of hormones and neurotransmitters, which are influenced by your genetics. If you have certain genetic variations, these signals might not be as strong or effective, leading to a persistent feeling of hunger even when your body has consumed enough energy. A coding variant (rs8040868 ) in acetylcholine receptors, which activate proopiomelanocortin neurons and melanocortin-4 receptors, is one example of how genetics can play a role.

8. Is a DNA test actually worth it for weight problems?

Currently, DNA tests can identify some genetic variants associated with weight, but they only explain a small portion of the overall picture. Many factors, including rare variants, complex gene interactions, and environmental influences, also contribute to weight. While a test might offer some insights into your predispositions, it won’t provide a complete roadmap for weight management due to the complexity and “missing heritability” of these traits.

9. Do my hormones make it harder for me to control my eating?

Yes, absolutely. Your hormones and neurotransmitters play a central role in controlling your hunger, satiety, and food cravings. Genetic factors influence the production, sensitivity, and signaling of these crucial biological messengers. This means that individual genetic differences can make it genuinely harder for some people to regulate their food intake compared to others.

10. Why do some diets work for others but not for me?

The effectiveness of a diet can be highly individual due to your unique genetic makeup, which influences your metabolism, appetite, and how your body processes different nutrients. What works well for one person might not be optimal for another because their underlying genetic predispositions for energy intake and expenditure differ. This is why personalized approaches to nutrition are gaining interest.

---

This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.

Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.

References

[1] Comuzzie AG. “Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.”PLoS One, 2012.

[2] Liu, JZ. “Genome-wide association study of height and body mass index in Australian twin families.”Twin Res Hum Genet, 2008.

[3] Xing, C. “A weighted false discovery rate control procedure reveals alleles at FOXA2that influence fasting glucose levels.”Am J Hum Genet, 2010.

[4] Scammell, BH. “Multi-ancestry genome-wide analysis identifies shared genetic effects and common genetic variants for self-reported sleep duration.” Hum Mol Genet, 2023.

[5] Carrasquillo, MM. “Genetic variation in PCDH11Xis associated with susceptibility to late-onset Alzheimer’s disease.”Nat Genet, 2009.

[6] Huang, J. “Cross-disorder genomewide analysis of schizophrenia, bipolar disorder, and depression.”Am J Psychiatry, 2010.

[7] Hwang LD et al. “New insight into human sweet taste: a genome-wide association study of the perception and intake of sweet substances.” Am J Clin Nutr. PMID: 31005972.

[8] Comuzzie AG et al. “Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.” PLoS One. PMID: 23251661.

[9] O’Rahilly, S., & Farooqi, I. S. “Human obesity as a heritable disorder of the central control of energy balance.”Int J Obes (Lond), vol. 32, suppl 7, 2008, pp. S55-S61.

[10] Butte, N. F., Christiansen, E., & Sorensen, T. I. “Energy imbalance underlying the development of childhood obesity.”Obesity, vol. 15, 2007, pp. 3056–3066.

[11] Velez Edwards, D. R., et al. “Gene-environment interactions and obesity traits among postmenopausal African-American and Hispanic women in the Women’s Health Initiative SHARe Study.”Hum Genet, vol. 132, no. 4, 2013, pp. 435–448.

[12] Fisher, J. O., Cai, G., Jaramillo, S., Cole, S. A., Comuzzie, A. G., et al. “Heritability of hyperphagic eating behavior and appetite-related hormones among Hispanic children.” Obesity, vol. 15, 2007, pp. 1484–1495.

[13] Hwang, L. D. “New insight into human sweet taste: a genome-wide association study of the perception and intake of sweet substances.” Am J Clin Nutr, vol. 109, no. 5, 2019, pp. 1324–1334.

[14] Johnson, R. K., Driscoll, P., & Goran, M. I. “Comparison of multiple-pass 24-hour recall estimates of energy intake with total energy expenditure determined by the doubly labeled water method in young children.”J Am Diet Assn, vol. 96, 1996, pp. 1140–1144.

[15] Ortega, R. M., Requejo, A. M., Andrés, P., López-Sobaler, A. M., Redondo, R., & González-Fernández, M. “Relationship between diet composition and body mass index in a group of Spanish adolescents.”Br J Nutr, vol. 74, no. 6, 1995, pp. 765–773.

[16] Butte, N. F., Cai, G., Cole, S. A., & Comuzzie, A. G. “VIVA LA FAMILIA Study: genetic and environmental contributions to childhood obesity and its comorbidities in the Hispanic population.”Am J Clin Nutr, vol. 84, 2006, pp. 646–654.

[17] Speliotes, E. K., Willer, C. J., Berndt, S. I., Monda, K. L., Thorleifsson, G., et al. “Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.”Nat Genet, vol. 42, 2010, pp. 937–948.

[18] Turcot, V, et al. “Protein-Altering Variants Associated with Body Mass Index Implicate Pathways That Control Energy Intake and Expenditure in Obesity.”Nature Genetics, vol. 50, no. 1, 2018, pp. 26–41.

[19] Chen, W. M., et al. “Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels.”J Clin Invest, vol. 118, no. 7, 2008, pp. 2623-34.

[20] Barsh, G. S., and M. W. Schwartz. “Genetic approaches to studying energy balance: perception and integration.” Nat Rev Genet, vol. 3, no. 8, 2002, pp. 589-600.

[21] Mineur, Y. S., et al. “Nicotine decreases food intake through activation of POMC neurons.” Science, vol. 332, no. 6035, 2011, pp. 1330-2.

[22] Stumpf, W. E., et al. “Target cells for 1,25-dihydroxyvitamin D3 in intestinal tract, stomach, kidney, skin, pituitary, and parathyroid.” Science, vol. 206, no. 4423, 1979, pp. 1188-90.

[23] Iynedjian, P. B. “Molecular physiology of mammalian glucokinase.”Cell Mol Life Sci, vol. 66, no. 1, 2009, pp. 27-42.

[24] Bikle, D. D., et al. “The vitamin D response element of the involucrin gene mediates its regulation by 1, 25-dihydroxyvitamin D3.”J Invest Dermatol, vol. 119, no. 5, 2002, pp. 1109-13.

[25] Blair, E., et al. “Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis.”Hum Mol Genet, vol. 10, no. 12, 2001, pp. 1215-20.

[26] Tonne, J. M., et al. “Global gene expression profiling of pancreatic islets in mice during streptozotocin-induced beta-cell damage and pancreatic Glp-1 gene therapy.” Dis Model Mech, vol. 6, no. 5, 2013, pp. 1236-45.

[27] Klenova, E. M., et al. “The novel BORIS+CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer.”Semin Cancer Biol, vol. 12, no. 5, 2002, pp. 399-414.

[28] Torrado, M., et al. “Clinical-etiologic correlation in children with Prader-Willi syndrome (PWS): an interdisciplinary study.” Am J Med Genet A, vol. 143, no. 5, 2007, pp. 460-8.

[29] Nettleton, JA, et al. “Associations Between Dietary Macronutrient Intake and Plasma Lipids Demonstrate Criterion Performance of the Multi-Ethnic Study of Atherosclerosis (MESA) Food-Frequency Questionnaire.”British Journal of Nutrition, vol. 102, 2009, pp. 1220–7.

[30] Patel, PS, et al. “Fatty Acids Measured in Plasma and Erythrocyte-Membrane Phospholipids and Derived by Food-Frequency Questionnaire and the Risk of New-Onset Type 2 Diabetes: A Pilot Study in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Cohort.”American Journal of Clinical Nutrition, vol. 92, 2010, pp. 1214–22.

[31] Hvidtfeldt, UA, et al. “Alcohol Intake and Risk of Coronary Heart Disease in Younger, Middle-Aged, and Older Adults.”Circulation, vol. 121, 2010, pp. 1589–1597.

[32] Mayer-Davis, EJ, et al. “Validity and Reproducibility of a Food Frequency Interview in a Multi-Cultural Epidemiology Study.” Annals of Epidemiology, vol. 9, 1999, pp. 314–24.

[33] Wright, JD, and CY Wang. “Trends in Intake of Energy and Macronutrients in Adults from 1999-2000 through 2007-2008.” NCHS Data Brief, National Center for Health Statistics, 2010.

[34] Hodson, L, et al. “Fatty Acid Composition of Adipose Tissue and Blood in Humans and Its Use as a Biomarker of Dietary Intake.” Progress in Lipid Research, vol. 47, 2008, pp. 348–380.