Advancements in informatics, genetics, and neuroscience have greatly expanded our understanding of how the central nervous system (CNS) regulates energy balance and metabolism. This chapter explores the key neural circuits within the hypothalamus and brainstem that integrate behavioral and physiological processes to maintain metabolic homeostasis. It also examines the dynamic interplay between the CNS and peripheral organs, mediated through hormonal and neuronal signals, which fine-tune appetite, energy expenditure, and body weight. Furthermore, we highlight groundbreaking research that unveils molecular and cellular pathways governing energy regulation, representing a new frontier in addressing obesity and metabolic disorders. Innovative approaches, such as neurogenetic and neuromodulation techniques, are explored as promising strategies for improving weight management and metabolic health. By providing a comprehensive perspective on the mechanisms underlying energy balance, this chapter underscores the transformative potential of emerging therapeutic innovations.

Colorectal cancer (CRC) represents the second leading cause of cancer incidence and the third leading cause of cancer deaths worldwide. There is currently a lack of understanding of the onset of CRC, hindering the development of effective prevention strategies, early detection methods and the selection of appropriate therapies. This article outlines the key aspects of host genetics currently known about the origin and development of CRC. The organisation of the colonic crypts is described. It discusses how the transformation of a normal cell to a cancer cell occurs and how that malignant cell can populate an entire colonic crypt, promoting colorectal carcinogenesis. Current knowledge about the cell of origin of CRC is discussed, and the two morphological pathways that can give rise to CRC, the classical and alternative pathways, are presented. Due to the molecular heterogeneity of CRC, each of these pathways has been associated with different molecular mechanisms, including chromosomal and microsatellite genetic instability, as well as the CpG island methylator phenotype. Finally, different CRC classification systems are described based on genetic, epigenetic and transcriptomic alterations, allowing diagnosis and treatment personalisation.

Food cravings, an intense desire to consume specific foods, are a complex interplay of cognitive, emotional, behavioral, physiological, and cultural factors. Although prevalent across genders, food cravings are more frequent and intense in women, with hormonal fluctuations-particularly during the menstrual cycle and pregnancy-playing a significant role. Pregnancy, marked by profound hormonal and physiological shifts, often heightens cravings, likely as a response to the increased metabolic needs of both mother and fetus. However, the tendency to crave high-calorie, palatable foods during this time can lead to excessive weight gain, presenting potential risks to both maternal and fetal health. This chapter examines the neural mechanisms underlying altered eating behaviors during pregnancy and their role in triggering food cravings. We discuss the health implications of disrupted eating patterns in pregnancy, emphasizing the need for further research to advance understanding of female-specific neurobiology and to develop targeted interventions that support healthy eating behaviors, ultimately improving maternal and offspring health outcomes.

Omics technologies are transforming our understanding of disease mechanisms and reshaping clinical practice. By enabling high-throughput, unbiased data collection at various molecular levels - including genes (genomics), mRNA (transcriptomics), proteins (proteomics), and metabolites (metabolomics) - omics approaches offer a comprehensive view of biological states in both health and disease. Among these, metabolomics has emerged as a pivotal tool, rapidly evolving beyond diagnostics to become a cutting-edge technique for pinpointing metabolites that regulate key physiological processes. This chapter reviews the advances in metabolomics, its integration with other omics approaches, and its applications, particularly emphasizing energy homeostasis. By incorporating metabolomic insights into physiology, we move closer to an integrative understanding of biological systems, laying the groundwork for novel therapies to combat obesity and related metabolic disorders.

Colorectal cancer (CRC) is the third leading cancer in incidence and the second leading cancer in mortality worldwide. There is growing scientific evidence to support the crucial role of the gut microbiota in the development of CRC. The gut microbiota is the complex community of microorganisms that inhabit the host gut in a symbiotic relationship. Diet plays a crucial role in modulating the risk of CRC, with a high intake of red and processed meat being a risk factor for the development of CRC. The production of metabolites derived from protein fermentation by the gut microbiota is considered a crucial element in the interaction between red and processed meat consumption and the development of CRC. This paper examines several metabolites derived from the bacterial fermentation of proteins associated with an increased risk of CRC. These metabolites include ammonia, polyamines, trimethylamine N-oxide (TMAO), N-nitroso compounds (NOC), hydrogen sulphide (HS), phenolic compounds (p-cresol) and indole compounds (indolimines). These compounds are depicted and reviewed for their association with CRC risk, possible mechanisms promoting carcinogenesis and their relationship with the gut microbiota. Additionally, this paper analyses the evidence related to the role of red and processed meat intake and CRC risk and the factors and pathways involved in bacterial proteolytic fermentation in the large intestine.

Coeliac disease (CD) is a chronic immune-mediated inflammatory disorder triggered by dietary gluten ingestion in genetically predisposed individuals. While gluten-specific T cells and HLA-DQ2/DQ8 alleles are critical to the disease onset, they account for less than half of the genetic heritability, underscoring the complexity of CD's genetic underpinnings. Genome-Wide Association Studies (GWAS) and next-generation sequencing have identified 42 non-HLA loci associated with CD risk, yet the molecular mechanisms underlying these associations remain largely unexplored. Notably, most disease-associated single nucleotide polymorphisms (SNPs) associated with CD are located in non-coding genomic regions, highlighting the regulatory potential of these variants. Emerging evidence demonstrates that non-coding RNAs (ncRNAs), particularly microRNAs and long non-coding RNAs, play crucial roles in gene regulation and disease development. Recent advances in transcriptomics have revealed new transcribed regions of the genome, shedding light on the functional significance of previously unannotated sequences. This review discusses the contribution of non-coding SNPs located in regulatory RNA regions to CD development, emphasizing the role of long non-coding RNAs and their potential as therapeutic targets.

Genetics is a significant risk factor for developing type 2 diabetes, with a family history conferring a 1.5-3-fold increased risk. Intriguingly, this heritable risk is higher when the affected parent is the mother, suggesting a potential role of mitochondrial genetics -maternally inherited DNA - in diabetes pathogenesis, a hypothesis this chapter will explore. While obesity mediates some of the genetic risk of type 2 diabetes, the chapter and will focus on genetic influences on diabetes independent of obesity. Mechanistically, genetic variants directly or indirectly contribute to insulin resistance across key tissues, including liver, muscle and adipose tissue. This insulin resistance prevents the liver from efficiently suppressing glucose production in response to insulin and impairs glucose uptake in muscle during postprandial states. Insulin resistance is driven by complex interactions between the genome and environmental, which can, in turn, influence gene expression and contribute to worsening of metabolic dysfunction. This chapter examines how tissue-specific genetic changes drive insulin resistance in individual organs and how these localized dysfunctions contribute to the broader, multi-organ metabolic dysfunction that characterize type 2 diabetes.

Colorectal cancer (CRC) is a heterogeneous disease with a complex aetiology influenced by a myriad of genetic and environmental factors. Despite advances in CRC research, it is a major burden of disease, with the second highest incidence and third leading cause of cancer deaths worldwide. To individualise diagnosis, prognosis, and treatment of CRC, developing new strategies combining precision medicine and bioinformatic procedures is promising. Precision medicine is based on omics technologies and aims to individualise the management of CRC based on patient host genetic characteristics and microbiota. Bioinformatics is central to the application of personalised medicine because it enables the analysis of large datasets generated by these technologies. At the level of host genetics, bioinformatics allows the identification of mutations, genes, molecular pathways, biomarkers and drugs relevant to colorectal carcinogenesis. At the microbiota level, bioinformatics is fundamental to analysing microbial communities' composition and functionality and developing biomarkers and personalised microbiota-based therapies. This paper explores the host and microbiota genetic data analysis in CRC research.

Complex traits, characterized by their reliance on multiple genetic variants and intricate environmental influences, present a unique challenge in the field of genetics. At the core of complex traits lies the interaction between numerous genetic variants-often polygenic in nature-and their regulation through epigenetic mechanisms. These mechanisms, which include DNA methylation, histone modification, and non-coding RNA activity, play a crucial role in gene expression and can significantly influence phenotypic outcomes. By examining how genetic and epigenetic elements interact, we can gain insight into the biological processes that underlie variation in complex traits. Ultimately, this chapter seeks to provide a comprehensive framework for understanding the multifaceted relationships between genetic and epigenetic factors in complex traits. By unraveling these interactions, we hope to pave the way for future research that can inform strategies for improving health outcomes and clinical practices.

Obesity is increasingly recognized not only for its systemic health impacts but also for its association with visual defects and eye diseases. This chapter explores the relationship between obesity and ocular health, highlighting the mechanisms by which metabolic dysregulation influences visual outcomes. Obesity exacerbates risk factors such as hypertension, dyslipidemia, and insulin resistance, which compromise retinal and optic nerve health. Conditions like diabetic retinopathy, age-related macular degeneration, and glaucoma are discussed in the context of obesity-related inflammation, oxidative stress, and altered vascular function, focusing on the retina as one of the body's most metabolically demanding tissues. Key pathways include adipose-derived cytokines that disrupt retinal homeostasis, and the effects of insulin resistance on retinal cells and vasculature. Furthermore, this chapter covers emerging evidence on the advances of genetic factors linking diabetic retinopathy to retinal impairments. By elucidating these interactions, we aim to provide insight into preventive and therapeutic strategies that could mitigate vision loss among individuals with obesity.

Throughout human history, pathogens have exerted great pressure on human genome that have defined susceptibility to both infectious and autoimmune diseases. This is possible because both type of conditions share susceptibility loci. The emergence of novel technologies that improves the genome analysis has greatly enhanced our ability to characterize in deeper the genetic architecture of human susceptibility to infectious diseases and autoimmune conditions. These genetic data sets identify outstanding informative overlaps that point to genetic modulation of immune function and inflammatory responses that affects both types of conditions. In this work, we revised single nucleotide polymorphisms and other genetic variations shared between these two categories of disease.

The post-genomic era has ushered in a transformative shift in biomedical research, driven by the integration of multi-omics technologies and advanced computational tools. While genome-wide association studies (GWAS) have identified thousands of variants linked to complex traits and diseases, the majority of these lie in non-coding regions, where their functional roles remain elusive. This chapter explores how fine-mapping, functional genomics, and systems biology are converging to bridge this gap, moving from statistical associations to mechanistic insights. Using celiac disease as a model, we illustrate how genomic, transcriptomic, epigenomic, and proteomic data can be harmonized to identify causal variants, prioritize candidate genes, and map regulatory networks that drive disease pathogenesis. We highlight the power of fine-mapping in refining GWAS signals and the importance of integrating chromatin accessibility, QTL colocalization, and single-cell omics to contextualize genetic risk within specific cellular environments. The chapter also discusses the promise of polygenic risk scores, the role of metabolomics in capturing functional phenotypes, and the emergence of single-cell and spatial technologies in revealing disease heterogeneity. Despite these advances, challenges remain-including data heterogeneity, computational complexity, and the underrepresentation of non-European populations in genomic studies. Addressing these issues will be critical for ensuring the equity and clinical utility of precision medicine. Ultimately, this chapter underscores the transformative potential of translational genomics. By connecting genetic variation to molecular function and clinical outcome, multi-omics approaches are paving the way for more predictive, preventive, and personalized healthcare-particularly in the context of autoimmune and other complex diseases.

The intestinal epithelium serves as a critical mechanical barrier against potentially pathogenic bacteria and their antigens while maintaining immune homeostasis and facilitating nutrient and water absorption. In the gut, T cells undergo a multitude of highly specialized differentiation processes which are influenced by the unique microenvironment. Several studies reveal that intestinal epithelial cells (IECs) not only provide signals that shape T cell responses but also express a variety of factors that modulate T cell activity, such as cytokines, chemokines, and antigen-presenting molecules. The crosstalk between T cells and intestinal epithelium is necessary to grant a delicate immune balance to prevent excessive inflammation while assuring tolerance towards commensal microbial communities. Disruption of this line of communication can be deleterious since it could lead to immune-inflammatory disorders such as inflammatory bowel disease (IBD) and other disorders such as colorectal cancer. In recent years, advanced genomic and transcriptomic technologies have partially untangled the regulatory networks underlying this interaction. Understanding how the mechanisms governing the regulation of the interaction between T cells and IECs offers potential therapeutic hints for enhancing mucosal immunity and treating related diseases affecting gastrointestinal health. This chapter explores the key cellular players of mucosal immunity and the importance of epithelial-T cell interactions for immune regulation and potential therapeutic applications.

Colorectal cancer (CRC) ranks second in incidence and third in cancer mortality worldwide. This situation, together with the understanding of the heterogeneity of the disease, has highlighted the need to develop a more individualised approach to its prevention, diagnosis and treatment through personalised medicine. This approach aims to stratify patients according to risk, predict disease progression and determine the most appropriate treatment. It is essential to identify patients who may respond adequately to treatment and those who may be resistant to treatment to avoid unnecessary therapies and minimise adverse side effects. Current research is focused on identifying biomarkers such as specific mutated genes, the type of mutations and molecular profiles critical for the individualisation of CRC diagnosis, prognosis and treatment guidance. In addition, the study of the intestinal microbiota as biomarkers is being incorporated due to the growing scientific evidence supporting its influence on this disease. This article comprehensively addresses the use of current and emerging diagnostic, prognostic and predictive biomarkers in precision medicine against CRC. The effects of host genetics and gut microbiota composition on new approaches to treating this disease are discussed. How the gut microbiota could mitigate the side effects of treatment is reviewed. In addition, strategies to modulate the gut microbiota, such as dietary interventions, antibiotics, and transplantation of faecal microbiota and phages, are discussed to improve CRC prevention and treatment. These findings provide a solid foundation for future research and improving the care of CRC patients.

Prader-Willi syndrome (PWS) is a complex genetic disorder arising from abnormalities on chromosome 15q11.2-q13, characterized by distinct physical, cognitive, and behavioral features that evolve across the lifespan. Early manifestations include severe hypotonia, feeding difficulties, and failure to thrive in infancy, progressing to hyperphagia, obesity, intellectual disabilities, and behavioral challenges in later stages. Additional features include growth hormone deficiency, short stature, delayed puberty, and other endocrine abnormalities. Genetic advances have illuminated the role of imprinted genes, such as SNORD116, in driving the syndrome's core features, offering insights into its variability and severity. Emerging research on targeted pathways, including oxytocin and ghrelin signaling, holds promise for innovative treatments addressing hyperphagia and behavioral symptoms. This chapter provides a comprehensive overview of PWS's clinical features, natural history, and molecular underpinnings, underscoring the importance of early diagnosis, multidisciplinary care, and precision medicine in optimizing outcomes and enhancing the quality of life for individuals with PWS.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death worldwide. In recent years, the impact of the gut microbiota on the development of CRC has become clear. The gut microbiota is the community of microorganisms living in the gut symbiotic relationship with the host. These microorganisms contribute to the development of CRC through various mechanisms that are not yet fully understood. Increasing scientific evidence suggests that metabolites produced by the gut microbiota may influence CRC development by exerting protective and deleterious effects. This article reviews the metabolites produced by the gut microbiota, which are derived from the intake of complex carbohydrates, proteins, dairy products, and phytochemicals from plant foods and are associated with a reduced risk of CRC. These metabolites include short-chain fatty acids (SCFAs), indole and its derivatives, conjugated linoleic acid (CLA) and polyphenols. Each metabolite, its association with CRC risk, the possible mechanisms by which they exert anti-tumour functions and their relationship with the gut microbiota are described. In addition, other gut microbiota-derived metabolites that are gaining importance for their role as CRC suppressors are included.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and nonmotor dysfunctions. Its pathological hallmark is the aggregation of ɑ-synuclein in the central nervous system (CNS), leading to widespread loss of dopaminergic neurons in the substantia nigra (SN). Interestingly, metabolic disorders localized in the periphery, such as diabetes mellitus, frequently co-occur with PD. Emerging evidence highlights a bidirectional relationship: metabolic diseases may accelerate PD progression, while PD can exacerbate metabolic dysfunction. Beyond these associations, a growing body of research suggests that dysfunction in the peripheral nervous system, the primary communication bridge between the brain and peripheral organs, plays a critical role in these comorbidities. Autonomic nerve perturbation may accelerate dopaminergic neuronal loss in the SN and exacerbate metabolic dysregulation. This chapter synthesizes current evidence linking autonomic dysfunction with the progression of PD and related metabolic disorders, and it explores innovative therapeutic strategies leveraging this bidirectional relationship to address PD progression.

Increasing scientific evidence demonstrates that gut microbiota plays an essential role in the onset and development of Colorectal cancer (CRC). However, the mechanisms by which these microorganisms contribute to cancer development are complex and far from completely clarified. Specifically, the impact of gut microbiota-derived metabolites on CRC is undeniable, exerting both protective and detrimental effects. This paper examines the effects and mechanisms by which important bacterial metabolites exert detrimental effects associated with increased risk of CRC. Metabolites considered include heterocyclic amines and polycyclic aromatic hydrocarbons, heme iron, secondary bile acids, ethanol, and aromatic amines. It is necessary to delve deeper into the mechanisms of action of these metabolites in CRC and identify the microbiota members involved in their production. Furthermore, since diet is the main factor capable of modifying the intestinal microbiota, conducting studies that include detailed descriptions of dietary interventions is crucial. All this knowledge is essential for developing precision nutrition strategies to optimise a protective intestinal microbiota against CRC.

Thermoregulation is a fundamental biological process that allows birds and mammals to maintain a stable internal temperature despite environmental fluctuations, a mechanism shaped by millions of years of evolution. Non-shivering thermogenesis (NST), primarily driven by brown adipose tissue (BAT), plays a central role in thermoregulation by not only helping maintain energy homeostasis but also influencing broader metabolic and physiological processes. Recent research has revealed that BAT thermogenesis is regulated by peripheral hormones and at a central level, with key hypothalamic energy-sensing pathways-such as AMP-activated protein kinase (AMPK) and endoplasmic reticulum (ER) stress-playing critical roles. Beyond its metabolic functions, BAT and NST have emerged as important contributors to tumor biology, offering novel therapeutic strategies for metabolic and oncological diseases. This review explores the intricate mechanisms underpinning NST, including UCP1-dependent thermogenesis and alternative pathways such as creatine cycling, calcium-dependent thermogenesis, and lipid cycling. Emerging evidence further highlights BAT's potential in to modulate tumor metabolism, with pharmacological and genetic approaches showing promise in reshaping the tumor microenvironment. This growing body of knowledge offers exciting prospects for targeting BAT thermogenesis in treating obesity and other metabolic diseases.

Despite recent advancements in colorectal cancer (CRC) treatment, particularly with the introduction of immunotherapy and checkpoint inhibitors, the efficacy of these therapies remains limited to a subset of patients. To address this challenge, our study aimed to develop a prognostic biomarker based on immune-related genes to predict better outcomes in CRC patients and aid in treatment decision-making. We comprehensively analysed immune gene expression signatures associated with CRC prognosis to construct an immune meta-signature with prognostic potential. Utilising data from The Cancer Genome Atlas (TCGA), we employed Cox regression to identify immune-related genes with prognostic significance from multiple studies. Subsequently, we compared the expression levels of immune genes, levels of immune cell infiltration, and various immune-related molecules between high-risk and low-risk patient groups. Functional analysis using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses provided insights into the biological pathways associated with the identified prognostic genes. Finally, we validated our findings using a separate CRC cohort from the Gene Expression Omnibus (GEO). Integration of the prognostic genes revealed significant disparities in survival outcomes. Differential expression analysis identified a set of immune-associated genes, which were further refined using LASSO penalisation and Cox regression. Univariate Cox regression analyses confirmed the autonomy of the gene signature as a prognostic indicator for CRC patient survival. Our risk prediction model effectively stratified CRC patients based on their prognosis, with the high-risk group showing enrichment in pro-oncogenic terms and pathways. Immune infiltration analysis revealed an augmented presence of certain immunosuppressive subsets in the high-risk group. Finally, we validated the performance of our prognostic model by applying the risk score equation to a different CRC patient dataset, confirming its prognostic potential in this new cohort. Overall, our study presents a novel immune-related gene signature with promising implications for predicting cancer progression and prognosis, thereby enabling more personalised management strategies for CRC patients.