Search Results (135)

Background/Objectives: Obesity, a major risk factor for cardiometabolic traits, is influenced by both genetic and environmental factors. Genetic studies have identified multiple single-nucleotide polymorphisms (SNPs) associated with obesity and related traits. This study aimed to examine the association between genetic risk score (GRS) and obesity-associated traits, while incorporating SNPs with established gene–diet interactions to explore their potential role in precision nutrition (PN) strategies. Methods: A total of 4279 participants were stratified into low- and intermediate-/high-GRS groups based on 18 SNPs linked to obesity and cardiometabolic traits. This study followed a case–control design, where cases included individuals with overweight/obesity, T2DM-positive (+), or CVD-positive (+) individuals and controls, which comprised individuals free of these traits. Logistic regression area under the curve (AUC) models were used to assess the predictive power of the GRS and traditional risk factors on BMI, T2DM and CVD. Results: Individuals in the intermediate-/high-GRS group had higher odds of being overweight or obese (OR = 1.23, CI: 1.03–1.48, p = 0.02), presenting as T2DM+ (OR = 1.56, CI: 1.03–2.49, p = 0.03) and exhibiting CVD-related traits (OR = 1.56, CI: 1.25–1.95, p < 0.0001), compared to the low-GRS group. The GRS was the second most predictive factor after age for BMI (AUC = 0.515; 95% CI: 0.462–0.538). The GRS also demonstrated a predictive power of 0.528 (95% CI: 0.508–0.564) for CVD and 0.548 (95% CI: 0.440–0.605) for T2DM. Conclusions: This study supports the potential utility of the GRS in assessing obesity and cardiometabolic risk, while emphasizing the potential of PN approaches in modulating genetic susceptibility. Incorporating gene–diet interactions provides actionable insights for personalized dietary strategies. Future research should integrate multiple gene–diet and gene–gene interactions to enhance risk prediction and targeted interventions. Full article

Background/Objectives: Obesity is associated with cardiovascular disease worldwide. An increased lipoprotein A (LpA) level is an independent risk factor for cardiovascular disease in children. Genetic polymorphisms of the LPA gene may play an important role in susceptibility to obesity. The aim of this study was to investigate the association of LPA rs10455872 polymorphism with the risk and clinical phenotypes of childhood obesity. Methods: This study included 103 children with obesity and 77 healthy controls. Genotyping of the LPA rs10455872 polymorphism was performed using real-time PCR. Results: The genotype distributions of the LPA rs10455872 polymorphism did not differ significantly between children with obesity and healthy children (p = 0.563). A marked difference in insulin levels was observed between children with obesity carrying the AG (16.90 IU/mL) and AA (25.57 IU/mL) genotypes. A marked difference was also observed in CRP levels between children with obesity with the AG (2.31 mg/L) and AA (4.25 mg/L) genotypes. After correcting for multiple comparisons using the false discovery rate (FDR), significant differences were found between AG and AA genotypes in vitamin B12 (adjusted p = 0.024). Serum iron showed a borderline association (adjusted p = 0.072). A statistically significant correlation was found between the metabolic syndrome index and body fat ratio among children with obesity with the AA genotype (p = 0.028). Conclusions: Although limited by the small number of children with obesity with the AG genotype, some differences were noted between the AG and AA genotypes. These exploratory findings require further investigation in adequately powered studies. In children with obesity with the AA genotype, the metabolic syndrome index increases as the body fat ratio increases. Full article

Gestational diabetes mellitus (GDM) occurs in approximately 9–25% of pregnancies and, if left undiagnosed or inadequately controlled, can lead to adverse outcomes for both the mother and the fetus, short and long term. GDM is characterized by glucose intolerance with onset or first recognition during pregnancy and is a multifactorial condition with a pathophysiology that remains incompletely understood. It is strongly associated with a chronic low-grade inflammatory state that contributes to insulin resistance, a hallmark of GDM pathogenesis. Among the fundamental pro-inflammatory cytokines implicated in this process, TNF-α and IL-6 play central roles. TNF-α is a cytokine primarily secreted by activated macrophages, as well as by adipocytes in the context of obesity. Many studies have shown that its levels are elevated in pregnant women with GDM compared to normoglycemic pregnant individuals. IL-6 is another pro-inflammatory cytokine secreted by immune cells, adipose tissue, and the placenta. It is found in higher concentrations in the maternal circulation during pregnancies complicated by GDM. Both TNF-α and IL-6 act synergistically to perpetuate a pro-inflammatory intrauterine environment. Their combined effects exacerbate insulin resistance and may impair pancreatic β-cell compensation during pregnancy, facilitating the onset of GDM in genetically or metabolically susceptible individuals. Recent research has identified various maternal serum biomarkers, such as TNF-α and IL-6, that may hold promise for the early detection of GDM. The aim of our study is to evaluate whether TNF-α and IL-6 can be used as diagnostic tools for the early diagnosis of GDM, allowing for timely intervention and reducing the risk of associated maternal and fetal complications. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD), the leading chronic liver condition globally, constitutes a major etiological contributor to hepatocellular carcinoma (HCC). Its transition from steatosis to non-alcoholic steatohepatitis (NASH) involves progressive fibrosis, ultimately predisposing to HCC. The pathogenesis involves multifactorial interactions among genetic susceptibility, environmental triggers, and obesity-associated metabolic dysregulation. Crucially, the gut–liver axis serves as a pivotal regulatory mechanism in MASLD development. Current therapeutic strategies prioritize lifestyle interventions for metabolic syndrome management, while pharmacological options remain limited, underscoring the need for new therapies. Emerging evidence highlights phenolic acids—bioactive phytochemicals from medicinal plants—as multi-target agents against MASLD. These compounds demonstrate therapeutic efficacy via antioxidative modulation of stress, anti-inflammatory activity, and gut–liver axis regulation. This review synthesizes recent advances in natural phenolic acids for MASLD intervention, emphasizing their potential as preventive and therapeutic candidates. Their multimodal mechanisms may inform innovative drug development paradigms targeting MASLD pathogenesis. Full article

Insulin resistance (IR) is a key mechanism underlying type 2 diabetes mellitus and is closely associated with obesity. Although numerous genome-wide association studies (GWASs) have identified variants that influence IR-related traits, it remains unclear whether the genetic architecture of IR differs according to obesity status. We conducted a stratified GWAS of the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) in 8906 Korean individuals from the Korean Genome and Epidemiology Study. Participants were categorized into a normal-weight group (Body Mass Index (BMI) ≤ 23 kg/m²) and an overweight or obese group (BMI > 23 kg/m²), and the GWAS was performed separately within each group. No significant genome-wide variants were identified in the normal-weight group; however, seven loci showed suggestive associations. In contrast, in the overweight and obese group, two loci, rs662799 in Apolipoprotein A5 (APOA5) and rs671 in Aldehyde Dehydrogenase 2 (ALDH2), showed genome-wide significance, with seven loci showing suggestive associations. The risk allele of rs662799 was associated with increased HOMA-IR values, with a stronger effect observed in the overweight and obese group. This finding aligns with the known role of APOA5 in triglyceride metabolism, suggesting that a higher BMI may exacerbate its effect on IR. These results highlight obesity-specific genetic susceptibility to IR and the need to consider obesity status in genetic studies of metabolic traits. Full article

Obesity is a global health challenge characterized by significant heterogeneity in causes and treatment responses, complicating sustainable management. This narrative review explores the genomic architecture of obesity and its implications for personalized interventions, focusing on how genetic variations influence key biological pathways and treatment outcomes. A comprehensive literature search, guided by the authors’ expertise, was conducted to identify key publications on the genomics of obesity and personalized approaches. The selection of articles prioritized those that provided direct insights into the genomic basis of obesity and its potential for informing tailored strategies. Genomic studies reveal both monogenic and polygenic influences on obesity, identifying numerous susceptibility loci. Genome-wide association studies (GWASs) have linked common variants in genes like FTO and MC4R to increased BMI and appetite dysregulation, respectively. Epigenetic research highlights the role of DNA methylation and other modifications in gene–environment interactions. Genetic and polygenic risk scores (GRSs and PRSs) show potential for refining risk stratification and predicting treatment response. The gut microbiome and metabolome also contribute to obesity pathogenesis, offering novel targets for intervention. Personalized medicine offers significant potential for improving obesity management through tailored interventions based on an individual’s genetic and ‘omics’ profile. Future research should focus on elucidating the functional consequences of identified variants, exploring gene–environment interactions, and developing strategies to overcome current limitations in clinical translation. With continued advancements, precision medicine can enhance treatment efficacy, increase sustainability, and help reduce the global burden of obesity-related diseases. Full article

Hirsutism, characterized by excessive terminal hair growth in androgen-sensitive areas, presents significant medical and psychosocial challenges in Gulf Cooperation Council (GCC) countries. This narrative review explores the epidemiology, endocrine factors, molecular basis of pathophysiology, cultural influences, and management approaches to hirsutism within the GCC. Regional factors such as consanguinity, rising obesity rates, and lifestyle habits contribute to a higher prevalence of hirsutism and related endocrine disorders, particularly polycystic ovary syndrome (PCOS). Cultural stigmas surrounding body hair further delay diagnosis and treatment, compounding psychological distress. The review examines the role of androgen excess, genetic susceptibility, and emerging molecular insights, including epigenetic dysregulations. Diagnostic limitations and the need for region-specific screening tools are discussed, alongside the current reliance on pharmacological, cosmetic, and traditional therapies. Public health initiatives targeting stigma reduction and early detection are emphasized. Future recommendations include culturally tailored research, enhanced public awareness, and the adoption of advanced diagnostic strategies to improve patient outcomes. This review aims to guide healthcare practices and inform policy development for the better management of hirsutism in the GCC context. Full article

Atrial fibrillation (AF) is the most prevalent sustained arrhythmia, associated with significant morbidity, mortality, and healthcare burdens. Despite therapeutic advances, recurrence rates remain high, particularly in persistent AF, underscoring the need for deeper mechanistic insight. Epigenetic regulation—comprising DNA methylation, histone modifications, chromatin remodeling, RNA methylation, and non-coding RNAs—has emerged as a key contributor to the structural, electrical, and inflammatory remodeling underlying AF. These mechanisms operate at the interface of genetic susceptibility and environmental exposure, offering a dynamic framework for understanding disease progression. Systemic stressors such as aging, obesity, diabetes, hypertension, hypoxia, and alcohol have been shown to induce epigenetic reprogramming in atrial tissue, further promoting atrial cardiomyopathy and arrhythmogenesis. Additionally, circulating epigenetic markers, particularly microRNAs, are being investigated for their potential in AF diagnosis, risk stratification, and therapeutic monitoring. Therapeutic strategies targeting epigenetic pathways—ranging from histone deacetylase inhibitors and miRNA-based therapeutics to CRISPR/dCas9-mediated epigenome editing—are under investigation. Additionally, sodium-glucose cotransporter 2 inhibitors may indirectly influence epigenetic programs and miRNA expression relevant to atrial remodeling. While promising, these approaches require further validation in terms of safety, delivery specificity, and long-term efficacy. High-resolution epigenomic mapping and integrative multi-omic approaches may enhance understanding of AF heterogeneity and enable personalized treatment strategies. This review provides an integrated appraisal of epigenetic mechanisms in AF and outlines their emerging diagnostic and therapeutic relevance. Full article

Background: Colonic diverticulosis is a common condition, particularly in the elderly population. While dietary habits, obesity, smoking, and physical inactivity contribute to its pathogenesis, emerging evidence highlights a genetic predisposition affecting extracellular matrix (ECM) remodeling, inflammation, and connective tissue integrity. The aim of this systematic review was to summarize genetic determinants of colonic diverticulosis. Methods: The PubMed^® database was searched for original studies in humans. The inclusion criteria were named genetic factor and confirmed diverticulosis. Patients with diverticulitis and diverticular diseases were excluded from this review. Results: Out of 137 publications, 10 articles met the inclusion criteria: six large association studies (GWAS) and four cross-sectional studies. The genes regulating ECM turnover, including TIMP1, MMP3, and MMP9, are involved in diverticulosis development. The TIMP1 (rs4898) T allele has been associated with increased susceptibility, potentially due to its role in ECM remodeling. Similarly, MMP3 (rs3025058) and MMP9 (rs3918242) polymorphisms contribute to altered collagen degradation. The COL3A1 (rs3134646) variant coding modified collagen type III may promote diverticular formation. Other genes, such as ARHGAP15 (rs4662344, rs6736741), affect cytoskeletal dynamics. Identified in GWAS studies, gene candidates may be grouped into blood group and immune system-related genes (ABO, HLA-DQA1, HLA-H, OAS1, TNFSF13, FADD), extracellular matrix and connective tissue genes (COL6A1, COLQ, EFEMP1, ELN, HAS2, TIMP2), signaling and cell communication (BMPR1B, WNT4, RHOU, PHGR1, PCSK5), nervous system and neurodevelopment (BDNF, CACNB2, GPR158, SIRT1, SCAPER, TRPS1), metabolism and transporters (SLC25A28, SLC35F3, RBKS, PPP1R14A, PPP1R16B), lipids and cholesterol (LDAH, LYPLAL1, STARD13), transcription and gene regulation (ZBTB4, UBTF, TNRC6B), apoptosis (FADD, PIAS1), and poorly characterized genes (C1TNF7, ENSG00000224849, ENSG00000251283, LINC01082, DISP2, SNX24, THEM4, UBL4B, UNC50, WDR70, SREK1IP1). Conclusions: There are a number of gene variants that probably predispose to colonic diverticulosis. Detailed characterization of the multigene background of diverticulosis will enable appropriate therapeutic or preventive interventions in the future. Full article

Background and Objectives: Despite their high prevalence, sarcopenia and sarcopenic obesity remain underdiagnosed worldwide, significantly impacting the health and quality of life of aging individuals. Due to their multifactorial nature, the current management strategies do not address their underlying pathogenesis. This systematic review aims to identify single-nucleotide polymorphisms (SNPs) associated with sarcopenia and/or sarcopenic obesity in humans. Materials and Methods. This systematic literature review followed the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)” guidelines and the protocol registered in PROSPERO. Extensive research was performed in six databases (PubMed, Web of Science, Cochrane Library, Scopus, ScienceDirect, and SpringerLink) using keywords such as “sarcopenia”, “sarcopenic obesity”, “single nucleotide polymorphisms”, “SNPs”, and “genetic variants”. The Q-Genie and ROBINS-E tools were utilized to assess the quality of the included studies. Results: The final analysis included 12 studies, which were classified as good-quality according to the Q-Genie assessment and indicated a low to moderate risk of bias according to the ROBINS-E evaluation, collectively identifying 43 SNPs significantly associated with sarcopenia or sarcopenic obesity. Specifically, 24 SNPs were linked to sarcopenia, while 19 were associated with sarcopenic obesity. Conclusions: Understanding the implications of SNPs provides valuable insights into individual susceptibility and the variability observed across populations, potentially leading to more targeted and effective diagnostic and treatment strategies. Advancing clinical practice requires ongoing research into the genetic aspects of sarcopenia and sarcopenic obesity. Full article

Nonalcoholic fatty liver disease (NAFLD) is a growing global health concern, impacting approximately 32.4% of the worldwide population. As a disease linked to metabolic dysfunction, NAFLD continues to rise alongside global increases in obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. There is considerable evidence indicating that NAFLD disproportionately affects racial, ethnic, and minority groups, although the exact reasons for these disparities remain elusive. Contributing factors to this disease may include socioeconomic status, cultural influences, stress, genetic factors, and lifestyle choices. Emerging evidence suggests that these causal factors could influence epigenetic mechanisms, particularly DNA methylation and histone modifications, as well as the composition and diversity of gut microbiota. Nevertheless, there is a scarcity of research that comprehensively examines the interplay between epigenetic changes and gut microbiome variations in relation to NAFLD disparities across different racial and ethnic populations globally. This paper intends to (i) explore the connections between NAFLD, ethnic disparities, gut microbiota composition, and epigenetic alterations, while reviewing pertinent studies that illustrate how these factors contribute to health inequities among various ethnic groups impacted by this disease; (ii) explore potential therapeutic targets and biomarkers to advance the management of NAFLD; and (iii) provide insights to enhance our understanding of the mechanisms associated with this disease, thereby promoting further research in this field. Advancements in this area are anticipated to enhance our understanding of disease susceptibilities in at-risk groups and to provide new therapeutic options for NAFLD and its associated complications. Full article

Current lifestyles bring about an increasing prevalence of unhealthy habits that can negatively affect male fertility. Cigarette smoking, alcohol intake, stress, inadequate physical activity, an unequilibrated diet leading to obesity, and use of mobile telephones and portable electronic devices can affect the male reproductive system through multiple mechanisms. Moreover, the modern man is often exposed to environmental factors independent of his will, such as air pollution, exposure to heat or toxicants in his workplace, or the presence of harmful chemicals in food, beverages, agricultural and industrial products, etc. The susceptibility to these factors depends on genetic and epigenetic predisposition, potentially present systemic disease and medication, and local affections of the genitourinary system. The multifaceted nature of both the causative factors and the susceptibility background makes the resulting fertility disturbance highly individual and variable among different men exposed to the same conditions. This paper critically reviews the current knowledge of different causative and susceptibility factors with a special attention to the molecular mechanisms of their action. Finally, strategies for the prevention of abnormalities due to lifestyle and environmental factors and available treatment modalities for already-present abnormalities are exposed. Full article

Obesity arises from a complex interplay of genetic and environmental factors. Even among individuals with the same genetic predisposition, diet-induced obesity (DIO) exhibits varying degrees of susceptibility, which are categorized as DIO and diet-induced obesity resistance (DR). The hypothalamus plays a pivotal role in regulating energy homeostasis. This study performed a comparative hypothalamic proteomic analysis in DIO and DR rats to identify differentially expressed proteins (DEPs) associated with alterations in body weight. Male Sprague Dawley rats were fed either a standard chow diet or a high-fat diet for 12 weeks. DIO rats exhibited the most rapid weight gain compared to both the control and DR rats. Despite consuming similar caloric intake, DR rats exhibited less weight gain relative to DIO rats. Proteomic analysis revealed 31 DEPs in the hypothalamus of DR rats compared to DIO rats (with a false discovery rate (FDR) < 1%). Notably, 14 proteins were upregulated and 17 proteins were downregulated in DR rats. Gene ontology analysis revealed an enrichment of ion-binding proteins, such as those binding to Fe²⁺, Zn²⁺, Ca²⁺, and Se, as well as proteins involved in neuronal activity and function, potentially enhancing neuronal development and cognition in DR rats. The DEPs pathway analysis via the Kyoto Encyclopedia of Genes and Genomes (KEGG) implicated starch and sucrose metabolism, antigen processing and presentation, and the regulation of inflammatory mediator affecting TRP channels. Western blotting confirmed the proteomic findings for TRPV4, CaMKV, RSBN1, and BASP1, which were consistent with those obtained from Tandem Mass tag (TMT) proteomic analysis. In conclusion, our study highlights the hypothalamic proteome as a critical determinant in the susceptibility to DIO and provides novel targets for obesity prevention and treatment. Full article

Type 2 diabetes (T2D) and metabolic syndrome (MetS) represent complex, multifactorial conditions that pose significant challenges to public health and healthcare costs worldwide. These two conditions share common risk factors such as obesity, dyslipidemia, and hypertension and, as a consequence, are frequently jointly diagnosed in an individual. More specifically, it is estimated that around 85% of T2D patients also have MetS, while patients diagnosed with MetS are five times as likely to develop T2D. While lifestyle and environmental factors, such as poor diet and physical inactivity, play a crucial role, genetic susceptibility also has a substantial influence on the overall risk. Recent advancements in genome-wide association studies (GWAS) have had a major impact on identifying numerous genetic loci associated with these conditions. This narrative review summarizes key findings from T2D and MetS genome-wide association studies, highlighting key genetic loci and pathways and their clinical implications. The objective of this review is to provide a comprehensive understanding of the known genetic underpinnings of T2D and MetS to inform future research and open potential therapeutic and preventive strategies. Full article

Sarcoidosis is a multi-system granulomatous disease of unknown etiology. In genetically susceptible individuals, the precipitating factors generate, via immunity mechanisms, a host granulomatous response. The granuloma, for unknown reasons thus far, may resolve or may persist and lead to organ damage and fibrosis. Infectious agents, occupational exposure, obesity, smoking and genetic factors are implicated in the pathogenesis of sarcoidosis. Macrophages are important in granuloma formation, and their M1/M2 phenotype is associated with the prognosis of the disease. CD4⁺ T helper cells play a central role in the pathogenesis of sarcoidosis. The major contributors appear to be Th1 and Th17.1 cells, whose microenvironmental behavior is dictated by the secretions of macrophages and dendritic cells. Higher levels of Th1 and Th17.1 cells are associated with chronic disease and resistance to corticosteroid treatment. In recent years, advances in the phenotyping of sarcoidosis with the help of HRCT, PET-CT and lung function tests have provided us with a better understanding of the disease. Genetic phenotyping performed by the GenPhenReSa consortium and the SAGA study has led to the recognition of new, distinct phenotypes. The reconstitution of dysregulated autophagy through persistent m-TORC-1 pathways may be a new treatment target in sarcoidosis. Full article