Leptin Receptor
Background
Section titled “Background”Leptin is a hormone primarily produced by adipose (fat) tissue, playing a critical role in regulating energy balance, appetite, and fat storage.[1]Its physiological effects are mediated through its specific binding to the leptin receptor, which is encoded by theLEPRgene. The identification and cloning of the leptin receptor, also known as OB-R, in the mid-1990s represented a pivotal moment in understanding the molecular mechanisms underlying metabolic regulation.[2]
Biological Basis
Section titled “Biological Basis”The leptin receptor (LEPR) is a transmembrane protein belonging to the class I cytokine receptor family. Upon binding with leptin, the receptor activates intracellular signaling pathways, most notably the JAK-STAT pathway. This activation transmits signals that influence various physiological processes, including appetite suppression, energy expenditure, and neuroendocrine function. Genetic variations within theLEPRgene can affect the receptor’s structure, function, or expression, thereby modulating the efficiency of leptin signaling and the body’s metabolic response. Beyond its direct role in energy homeostasis, the leptin receptor system is also intricately linked to inflammatory processes. For example, C-reactive protein (CRP), a well-known marker of inflammation, has been shown to interact directly with leptin, potentially leading to leptin resistance.[3] Furthermore, genetic variability at the LEPRlocus has been found to be a determinant of plasma levels of inflammatory markers such as fibrinogen and C-reactive protein.[4]
Clinical Relevance
Section titled “Clinical Relevance”Dysregulation of the leptin-leptin receptor pathway has significant clinical implications. Alterations in leptin signaling are often associated with conditions such as obesity and type 2 diabetes.[5] Genetic variations in LEPRare linked to circulating levels of C-reactive protein and fibrinogen, both of which are established risk factors for cardiovascular disease.[4] Research has identified specific genetic loci, including those involving LEPR, within metabolic-syndrome pathways that are associated with plasma C-reactive protein levels.[6]Elevated plasma leptin levels themselves have been correlated with an increased risk of cardiovascular disease.[7]Additionally, studies indicate an interrelationship between serum leptin concentrations and the expression of serum amyloid A (SAA) in adipose tissue, highlighting its broader involvement in acute-phase inflammatory responses.[1]Understanding these connections is crucial for comprehending the complex interplay between metabolism, inflammation, and cardiovascular health.
Social Importance
Section titled “Social Importance”The global prevalence of obesity, metabolic syndrome, and cardiovascular diseases underscores the substantial social importance of research into the leptin receptor. By elucidating the genetic and biological factors that govern energy balance and inflammatory responses, studies on theLEPR gene contribute to a deeper understanding of individual susceptibility to these widespread health challenges. This knowledge can facilitate the development of personalized diagnostic tools, risk assessment strategies, and targeted therapeutic interventions for metabolic and inflammatory conditions, ultimately aiming to improve public health outcomes and enhance the quality of life for affected individuals.
Methodological and Statistical Constraints
Section titled “Methodological and Statistical Constraints”The genetic study of complex traits like leptin receptor is subject to several methodological and statistical limitations that can impact the reliability and interpretation of findings. Many genetic variants associated with such traits often exert only small individual effects, necessitating extremely large sample sizes to achieve sufficient statistical power for detection. Smaller studies risk missing genuine associations or reporting inflated effect sizes that may not consistently replicate in independent cohorts, underscoring the critical role of replication studies in validating initial discoveries.[8] Furthermore, the extensive number of genetic markers analyzed in genome-wide association studies (GWAS) mandates stringent corrections for multiple testing, such as the Bonferroni method, which, while reducing false positives, can be overly conservative and potentially increase the rate of false negatives.[8]Careful adjustment for potential confounders is essential to prevent spurious associations. Variables such as age, sex, body composition, lifestyle factors (e.g., smoking status, medication use), and especially population stratification, must be meticulously controlled. While advanced statistical methods like EIGENSTRAT and the calculation of genomic inflation factors (lambda) are employed to account for population substructure, inadequate control can still lead to misleading results.[8] The quality of genotyping data, including call rates and adherence to Hardy-Weinberg equilibrium, also directly influences the integrity of the association analyses.[9]
Population Specificity and Phenotypic Complexity
Section titled “Population Specificity and Phenotypic Complexity”A significant limitation in understanding the genetic basis of traits like leptin receptor is the challenge of generalizability across diverse populations. Historically, many large-scale genetic studies have predominantly included individuals of European ancestry, meaning that findings may not directly translate to other ethnic groups where genetic architectures, allele frequencies, and linkage disequilibrium patterns can differ substantially.[8] This lack of ancestral diversity limits the comprehensive understanding of genetic influences globally and highlights the need for more inclusive research to identify population-specific and universally relevant genetic variants.
The precise definition and consistent of the phenotype itself are also critical. For a complex trait like leptin receptor , variations in how the trait is assessed, the assays used, and the clinical or laboratory protocols applied across different studies can introduce considerable heterogeneity. Such inconsistencies can obscure true genetic signals and complicate the meta-analysis of data from multiple cohorts. Even minor discrepancies in data collection or quality control procedures can impact the robustness and comparability of results, emphasizing the importance of standardized and high-quality phenotyping.[9]
The Role of Environmental Factors and Unexplained Heritability
Section titled “The Role of Environmental Factors and Unexplained Heritability”The genetic landscape of complex traits is rarely straightforward, often involving intricate interactions between an individual’s genetic makeup and their environment. While research endeavors to control for known environmental covariates, such as diet, physical activity, and socioeconomic indicators, fully characterizing and modeling complex gene-environment (GxE) interactions remains a considerable challenge.[10] Unaccounted or poorly measured environmental factors can confound genetic associations, leading to an incomplete picture of a variant’s true effect or masking its influence entirely, thereby limiting the predictive power of genetic models.
Despite the identification of numerous genetic loci through GWAS, these variants typically explain only a modest fraction of the total heritable variation for complex traits, a phenomenon commonly referred to as “missing heritability.” This suggests that a substantial portion of the genetic influence on traits like leptin receptor arises from many more common variants with individually minute effects, rarer variants not adequately captured by current genotyping platforms, or more complex genetic architectures involving gene-gene interactions that are difficult to detect with current methodologies.[11] A complete understanding of the genetic underpinnings requires further exploration into these polygenic effects and the potential synergistic actions of multiple genes.
Variants
Section titled “Variants”The LEPRgene provides instructions for making the leptin receptor, a protein essential for binding leptin, a hormone that signals satiety and regulates energy balance. Genetic variations withinLEPR, such as rs12077336 , rs2376018 , and rs79035087 , can influence how effectively leptin signals to the brain, impacting appetite control and metabolic rate. These variants may alter the structure or abundance of the leptin receptor, thereby affecting an individual’s sensitivity to leptin and their predisposition to conditions like obesity. Similarly, variants in theLEPR - RN7SL854P locus, including rs183790625 , rs11805970 , and rs111313184 , could affect the broader regulatory landscape of leptin signaling, potentially influencing circulating leptin receptor levels and overall metabolic health.[12]Such genetic differences are important for understanding the variability in leptin receptor levels and their implications for metabolic health.[13]Several other genes contribute to metabolic processes that can indirectly influence leptin signaling and overall energy homeostasis. TheGCKRgene encodes glucokinase regulatory protein, which controls the activity of glucokinase, a key enzyme in glucose metabolism; thers1260326 variant in GCKRis associated with altered glucose and triglyceride levels, suggesting a role in nutrient sensing and storage.APOH codes for apolipoprotein H, involved in lipid metabolism and coagulation; the rs1801689 variant in APOHmay affect lipid profiles, which are often dysregulated in conditions of leptin resistance.SERPINA1 produces alpha-1 antitrypsin, a proteinase inhibitor with anti-inflammatory properties, and its rs28929474 variant could impact inflammatory responses known to contribute to metabolic dysfunction and leptin resistance. Furthermore, theRPL31P23 - PCCB locus, including rs1154988 , involves the PCCBgene, which is critical for the metabolism of certain amino acids and fatty acids, linking it to broader energy metabolism and potentially influencing the metabolic environment in which leptin receptor signaling operates.[13]These genetic variations highlight the complex interplay of genes in maintaining metabolic balance and impacting leptin receptor function.[14]Beyond direct metabolic regulators, genes involved in development and cellular function can also impact traits overlapping with leptin receptor biology. TheTRPS1 gene, with its rs2049865 variant, is a transcription factor important for skeletal development and hair follicle formation, and disruptions can lead to broader metabolic implications. The RPL7AP64 - ASGR1 region, including rs186021206 , involves ASGR1(asialoglycoprotein receptor 1), which plays a role in glycoprotein metabolism and liver function, potentially influencing systemic metabolic cues.HNF1A-AS1 is a long non-coding RNA that can regulate the HNF1Agene, a master regulator of pancreatic beta-cell function and glucose homeostasis; thers2464190 variant might thus indirectly affect glucose metabolism and insulin sensitivity, which are intertwined with leptin action. Lastly, theBCL7B - TBL2 region, with variant rs111269058 , involves genes with roles in cell growth and signaling, whose subtle variations could contribute to the complex interplay of factors influencing body composition and metabolic health, thereby indirectly impacting leptin receptor function.[12]These diverse genetic influences underscore the multifaceted nature of metabolic regulation and its connection to leptin signaling and its receptor.[14]
Key Variants
Section titled “Key Variants”Defining the Leptin Receptor and its Nomenclature
Section titled “Defining the Leptin Receptor and its Nomenclature”The leptin receptor, commonly referred to asOB-R, is a crucial transmembrane protein that serves as the primary mediator for the biological actions of leptin. Leptin itself is a hormone predominantly secreted by adipose tissue, playing a vital role in the regulation of energy homeostasis and various metabolic processes.[2] The gene encoding this receptor is officially designated as LEPR. The initial identification and expression cloning of the OB-Rin 1995 represented a significant milestone, providing the molecular basis for understanding how leptin exerts its systemic effects.[2]Precise terminology and a clear understanding of the leptin receptor’s definition are essential to differentiate it from the leptin hormone and other components of the complex signaling pathways it influences.
Genetic Classification and Functional Implications
Section titled “Genetic Classification and Functional Implications”The primary system for classifying the leptin receptor, particularly in human studies, centers on the genetic variability found within theLEPR gene locus. Research consistently demonstrates that specific genetic variants at the LEPRlocus are significant determinants of various physiological parameters, including circulating levels of plasma fibrinogen and C-reactive protein (CRP).[4]These genetic differences can lead to diverse functional impacts on leptin signaling efficiency and sensitivity, thereby influencing an individual’s metabolic profile and their predisposition to conditions such as chronic inflammation and cardiovascular disease.[4]This genotypic classification offers a categorical framework for assessing inherent variations in leptin receptor function among individuals, moving beyond a simple presence or absence to consider the specific qualitative and quantitative effects of distinct genetic alleles.
Approaches to Leptin Receptor Assessment and Clinical Significance
Section titled “Approaches to Leptin Receptor Assessment and Clinical Significance”of the leptin receptor, or its functional status, primarily involves assessing genetic variations within theLEPR locus and correlating these with relevant clinical biomarkers. Studies have established that genetic variability at the LEPRlocus acts as a critical determinant of plasma fibrinogen and C-reactive protein (CRP) levels.[4]These biomarkers, especially CRP, are widely recognized as indicators of systemic inflammation and are predictive of cardiovascular disease risk.[15] Consequently, while direct protein quantification of all LEPRisoforms can be complex, the operational definition of leptin receptor assessment often includes genotyping specificLEPR variants and linking them to these clinically significant circulating markers, recognizing their involvement in metabolic syndrome pathways.[6]The functional integrity of the leptin receptor holds substantial clinical significance, as its dysregulation can result in conditions like leptin resistance, which has been shown to arise from a direct interaction with C-reactive protein.[3]
Leptin and its Receptor: Core Regulatory Mechanisms
Section titled “Leptin and its Receptor: Core Regulatory Mechanisms”Leptin, a crucial hormone primarily synthesized by adipose tissue, plays a fundamental role in regulating energy balance, appetite, and overall body weight. Its physiological actions are mediated through its interaction with the leptin receptor, known asLEPR or OB-R, which was first identified and cloned in 1995.[2]This receptor acts as the primary transducer for leptin’s signals, initiating complex intracellular pathways that govern various metabolic processes throughout the body.[16]The binding of leptin toLEPR triggers a cascade of molecular events essential for maintaining energy homeostasis and coordinating metabolic responses across different tissues.
Genetic Influences on Leptin Receptor and Metabolic Health
Section titled “Genetic Influences on Leptin Receptor and Metabolic Health”Genetic variations within the LEPR gene locus significantly contribute to an individual’s metabolic profile and susceptibility to metabolic disturbances. Studies have demonstrated that genetic variability at the LEPRlocus acts as a determinant for circulating levels of plasma fibrinogen and C-reactive protein, both of which are key biomarkers associated with inflammation and cardiovascular risk.[4] These genetic mechanisms highlight how inherited differences in the LEPR gene can influence the intricate regulatory networks that govern systemic metabolic and inflammatory responses, potentially predisposing individuals to certain health outcomes.[6] The precise genetic makeup at this locus therefore plays a role in shaping a person’s metabolic health.
Leptin Receptor, Inflammation, and Metabolic Interplay
Section titled “Leptin Receptor, Inflammation, and Metabolic Interplay”The leptin receptor system is not solely involved in energy balance but also intricately connected with inflammatory processes, illustrating a significant interplay between metabolic and immune functions. C-reactive protein (CRP), a prominent acute-phase protein and a widely recognized marker of systemic inflammation, can directly interact with leptin, thereby inducing a state of leptin resistance within the body.[3]This interaction represents a critical molecular mechanism through which inflammation can disrupt the normal responsiveness to leptin, potentially contributing to metabolic dysregulation. Furthermore, serum concentrations and expressions of leptin and serum amyloid A (SAA), another acute-phase protein, are interrelated, particularly within adipose tissue, suggesting a local and systemic cross-talk between adipocyte function, leptin signaling, and broader inflammatory responses.[1] This complex network also involves other inflammatory mediators, such as interleukin-6 (IL-6), whose receptor (IL6R) is associated with metabolic-syndrome pathways and plasma CRP levels, further emphasizing the interconnectedness of these systems.[6]
Pathophysiological Relevance in Cardiometabolic Diseases
Section titled “Pathophysiological Relevance in Cardiometabolic Diseases”Dysregulation of leptin receptor signaling and its associated molecular pathways is a central factor in the pathophysiology of numerous chronic conditions, particularly those within the cardiometabolic disease spectrum. Leptin resistance, often exacerbated by inflammatory mediators like CRP, contributes significantly to the homeostatic imbalances characteristic of metabolic syndrome and type 2 diabetes mellitus.[3] Genetic loci, including LEPR, along with HNF1A, IL6R, and GCKR, which are implicated in metabolic-syndrome pathways, have been consistently linked to elevated plasma C-reactive protein levels and an increased risk of coronary heart disease.[6]These associations underscore the profound systemic consequences of altered leptin signaling and chronic inflammation on overall cardiovascular health, highlighting the leptin receptor system as a crucial component in understanding and addressing these widespread diseases.[7]
Leptin Receptor Signaling and Metabolic Control
Section titled “Leptin Receptor Signaling and Metabolic Control”The leptin receptor, identified asOB-R or LEPR, acts as a crucial transducer of signals from the adipokine leptin, a hormone central to energy homeostasis.[2]Upon leptin binding,LEPRinitiates intracellular signaling cascades, although the specific components are not detailed in these studies, these pathways are known to regulate various aspects of energy metabolism, including appetite suppression and energy expenditure. This receptor activation influences metabolic regulation across tissues, impacting processes like biosynthesis and catabolism to maintain energy balance.
The functional significance of LEPR extends to broader metabolic pathways, as genetic variability at the LEPR locus is associated with pathways involved in metabolic syndrome.[6]Leptin, through its receptor, plays a role in the intricate flux control of nutrients and energy substrates, influencing body weight and fat mass. The interrelation between serum concentrations and expressions of serum amyloid A and leptin in adipose tissue further highlights the leptin receptor’s involvement in integrated metabolic responses.[1]
Genetic and Post-Translational Regulation
Section titled “Genetic and Post-Translational Regulation”The expression and function of the leptin receptor are subject to tight regulatory mechanisms, including genetic variability at theLEPRlocus itself. Such genetic variations are significant determinants of circulating levels of inflammatory markers like plasma fibrinogen and C-reactive protein.[4]These genetic predispositions can influence the overall signaling efficiency and downstream effects of leptin, thereby modulating an individual’s metabolic and inflammatory profiles.
Beyond genetic regulation, post-translational modifications of the leptin receptor and its interacting proteins can further fine-tune its activity and the intracellular signaling cascades. Such mechanisms are common for cytokine receptors likeLEPRand are critical for controlling receptor sensitivity, signal strength, and feedback loops that prevent overstimulation or desensitization. These regulatory layers collectively contribute to the precise control of leptin’s biological actions.
Pathway Crosstalk and Inflammatory Interactions
Section titled “Pathway Crosstalk and Inflammatory Interactions”The leptin receptor pathways do not operate in isolation but are intricately integrated within a broader network of physiological signaling, particularly with inflammatory pathways. A key example of this systems-level integration is the direct interaction between C-reactive protein (CRP) and leptin, which can induce leptin resistance.[3]This crosstalk represents a significant mechanism where inflammation directly modulates metabolic signaling, impairing leptin’s ability to exert its homeostatic effects.
Furthermore, the LEPR locus, along with other genes like HNF1A, IL6R, and GCKR, are associated with plasma C-reactive protein levels, indicating a shared regulatory landscape between metabolic and inflammatory processes.[6]Interleukin-6 (IL-6), another inflammatory cytokine, and its soluble receptor are known to be elevated in metabolic conditions like type 2 diabetes mellitus, suggesting a broader inflammatory milieu that can interact with and influence leptin signaling and receptor function.[5] These complex network interactions highlight the hierarchical regulation where inflammatory signals can exert emergent properties on metabolic control.
Disease-Relevant Mechanisms and Therapeutic Implications
Section titled “Disease-Relevant Mechanisms and Therapeutic Implications”Dysregulation of the leptin receptor pathway is a central mechanism in the pathogenesis of several metabolic and cardiovascular diseases. Genetic variability at theLEPRlocus is a known determinant of plasma fibrinogen and C-reactive protein levels, both of which are established markers and risk factors for cardiovascular disease.[4]The direct link between plasma leptin levels and the risk of cardiovascular disease further underscores the clinical relevance of this pathway.[7]The induction of leptin resistance by inflammatory mediators like CRP represents a compensatory mechanism that, while potentially protective in acute settings, contributes to chronic metabolic dysfunction.[3]Understanding these pathway dysregulations provides insights into potential therapeutic targets for conditions such as metabolic syndrome and coronary heart disease. Modulating leptin receptor sensitivity or interrupting the inflammatory crosstalk could offer novel strategies to restore metabolic balance and mitigate disease progression.
Role in Metabolic and Cardiovascular Risk Stratification
Section titled “Role in Metabolic and Cardiovascular Risk Stratification”Genetic variability at the LEPRlocus is a determinant of plasma fibrinogen and C-reactive protein (CRP) levels, both of which are established markers associated with cardiovascular disease risk.[4] Specific genetic loci within metabolic-syndrome pathways, including LEPR, further associate with plasma CRP levels.[6] These associations suggest that analyzing LEPRvariants could serve as a valuable tool for identifying individuals at an increased risk for metabolic syndrome components and subsequent cardiovascular complications, allowing for earlier intervention and personalized preventive strategies.[17] The integration of LEPRgenetic information into clinical assessments offers prognostic insights into long-term cardiovascular health outcomes. By stratifying individuals based on theirLEPRstatus, clinicians may enhance risk prediction beyond traditional factors, identifying high-risk individuals who could benefit from intensive lifestyle modifications or targeted pharmacological interventions. This approach supports personalized medicine by tailoring prevention strategies to an individual’s genetic predisposition to inflammation and metabolic dysregulation, potentially mitigating disease progression and improving overall patient care.
Leptin Receptor and Inflammatory Pathways
Section titled “Leptin Receptor and Inflammatory Pathways”The leptin receptor plays a critical role in inflammatory processes, with genetic variability at theLEPRlocus influencing circulating levels of key inflammatory markers such as C-reactive protein and fibrinogen.[4]A notable interaction involves C-reactive protein directly inducing leptin resistance, establishing a complex feedback loop that can perpetuate chronic inflammation and contribute to the progression of various diseases.[3]This mechanism highlights the central position of the leptin signaling pathway in the body’s inflammatory response.
Furthermore, studies indicate an interrelationship between serum concentrations and expressions of serum amyloid A and leptin in adipose tissue, suggestingLEPR’s broader involvement in inflammatory and metabolic responses.[1]This includes conditions like type 2 diabetes mellitus, where alterations in interleukin-6 pathways are observed and contribute to systemic inflammation.[5] Understanding these intricate interactions provides a foundation for the diagnostic utility of LEPRanalysis in identifying patients with dysregulated inflammatory responses linked to compromised leptin signaling, facilitating more precise clinical assessments of inflammatory comorbidities.
Clinical Implications for Disease Management
Section titled “Clinical Implications for Disease Management”The clinical relevance of LEPR extends to guiding personalized medicine approaches, where the identification of specific LEPR genetic variants could inform treatment selection and monitoring strategies for conditions characterized by chronic inflammation and metabolic dysfunction.[6]This allows for a more targeted therapeutic approach, moving beyond a one-size-fits-all model. For instance, in patients identified as being at high risk for coronary heart disease due to theirLEPR profile, monitoring of CRP levels, which are influenced by LEPRloci, could guide adjustments in therapeutic interventions aimed at reducing cardiovascular risk.[17]By providing insights into an individual’s predisposition to inflammation and leptin resistance,LEPRanalysis can support the development of more effective and tailored interventions. This could lead to improved patient outcomes by preventing severe long-term complications associated with metabolic and cardiovascular disorders.[3] Such personalized strategies can optimize the management of complex conditions, enhancing the efficacy of treatment and improving the quality of life for affected individuals.
Frequently Asked Questions About Leptin Receptor
Section titled “Frequently Asked Questions About Leptin Receptor”These questions address the most important and specific aspects of leptin receptor based on current genetic research.
1. Why can’t I lose weight even when my friend eats less?
Section titled “1. Why can’t I lose weight even when my friend eats less?”Your body’s response to food can be influenced by genetic variations in your leptin receptor. These variations can affect how efficiently your body signals satiety and regulates energy, making weight management different for everyone, even if you eat less.
2. Why do some people never gain weight no matter what they eat?
Section titled “2. Why do some people never gain weight no matter what they eat?”Just like some people struggle, others have genetic variations in their leptin receptor that make their body very efficient at regulating appetite and energy expenditure. This can lead to a naturally leaner physique, even with varied eating habits.
3. Does my body sometimes ignore signals to stop eating?
Section titled “3. Does my body sometimes ignore signals to stop eating?”Yes, it’s possible. Sometimes, inflammatory markers like C-reactive protein can interfere with leptin’s ability to bind to its receptor, potentially leading to leptin resistance. This means your brain might not effectively receive the “full” signal.
4. My sibling is thin but I’m not – why the difference?
Section titled “4. My sibling is thin but I’m not – why the difference?”Even within families, individual genetic variations in the leptin receptor gene can differ, leading to distinct metabolic responses. These subtle genetic differences can significantly influence how each person’s body handles energy and fat storage.
5. Will my kids inherit my struggles with weight?
Section titled “5. Will my kids inherit my struggles with weight?”There’s a genetic component to how your body regulates weight, partly due to the leptin receptor gene (LEPR). While your children might inherit some predispositions, lifestyle and environmental factors also play a significant role in their overall health outcomes.
6. Could my chronic inflammation be linked to my weight?
Section titled “6. Could my chronic inflammation be linked to my weight?”Absolutely. Genetic variations in your leptin receptor are linked to plasma levels of inflammatory markers like C-reactive protein and fibrinogen. This highlights a strong interplay between your metabolism and inflammatory responses.
7. Am I at higher heart risk because of my weight?
Section titled “7. Am I at higher heart risk because of my weight?”Elevated plasma leptin levels themselves have been correlated with an increased risk of cardiovascular disease. Additionally, genetic variations in your leptin receptor are linked to established risk factors for heart disease, such as high C-reactive protein and fibrinogen.
8. I’m from a different background – does that affect my weight risk?
Section titled “8. I’m from a different background – does that affect my weight risk?”Yes, it can. Many large genetic studies have predominantly focused on individuals of European ancestry, meaning findings might not directly translate to other ethnic groups where genetic patterns can differ substantially. More inclusive research is needed for a full understanding.
9. Is a DNA test actually worth it for weight problems?
Section titled “9. Is a DNA test actually worth it for weight problems?”Understanding your genetic profile, including variations in your leptin receptor (LEPR), can be valuable. This knowledge can contribute to personalized diagnostic tools and risk assessments, potentially guiding more targeted strategies for managing your weight and metabolic health.
10. Can exercise really overcome bad family history?
Section titled “10. Can exercise really overcome bad family history?”While genetics, including variations in your leptin receptor, play a role in your predisposition to weight-related issues, lifestyle factors like exercise are incredibly important. Consistent healthy habits can significantly influence how your genes are expressed and impact your overall metabolic health.
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
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[2] Tartaglia, L. A., et al. “Identification and expression cloning of a leptin receptor, OB-R.”Cell, vol. 83, 1995, pp. 1263–1271.
[3] Chen, K., et al. “Induction of leptin resistance through direct interac- tion of C-reactive protein with leptin.”Nat. Med., vol. 12, 2006, pp. 425–432.
[4] Zhang, Y. Y., et al. “Genetic variability at the leptin receptor (LEPR) locus is a determinant of plasma fibrinogen and C-reactive protein levels.”Atherosclerosis, vol. 191, 2007, pp. 121–127.
[5] Kado, S., et al. “Circulating levels of interleukin-6, its soluble receptor and interleukin-6/inter-leukin-6 receptor complexes in patients with type 2 diabetes mellitus.”Acta Diabetol., vol. 36, 1999, pp. 67–72.
[6] Ridker, P. M., et al. “Loci related to metabolic-syndrome pathways including LEPR, HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women’s Genome Health Study.”Am J Hum Genet, 2008.
[7] Wallace, A. M., et al. “Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS).”Circulation, vol. 104, 2001, pp. 3052–3056.
[8] Liu, X.G. et al. “Genome-wide association and replication studies identified TRHR as an important gene for lean body mass.”Am J Hum Genet, vol. 84, no. 3, 2009, pp. 417-422.
[9] Suchindran, S. et al. “Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study.” PLoS Genet, vol. 6, no. 5, 2010.
[10] Loya, H. et al. “A scalable variational inference approach for increased mixed-model association power.” Nat Genet, 2024.
[11] Liu, J.Z. et al. “Genome-wide association study of height and body mass index in Australian twin families.”Twin Res Hum Genet, vol. 13, no. 2, 2010, pp. 159-170.
[12] Fox CS et al. “Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project.”BMC Med Genet, 2007.
[13] Comuzzie AG et al. “Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.”PLoS One, 2012.
[14] Lowe JK et al. “Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae.” PLoS Genet, 2009.
[15] Ridker, P. M., et al. “C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women.”N Engl J Med, vol. 342, 2000, pp. 836–843.
[16] Tartaglia, L. A. “The leptin receptor.”J Biol Chem, vol. 272, 1997, pp. 6093–6096.
[17] Elliott, P, et al. “Genetic Loci associated with C-reactive protein levels and risk of coronary heart disease.”JAMA, vol. 302, 2009, pp. 37–48.