Takayuki Kannon

BACKGROUND: Oxytocin (OXT) signaling through the oxytocin receptor (OXTR) produces stress-relieving effects and modulates alcohol reward and sucrose preference in animal models. These findings suggest the therapeutic potential of OXT for alcohol use disorder (AUD) and liver steatosis. However, human genetic evidence linking OXT signaling to these cravings remains scarce. OBJECTIVE: This study examined the association between the OXTR rs53576 polymorphism and habitual intake of alcohol and sucrose in a general population, with a further focus on related liver pathology. METHODS: A cross-sectional analysis was conducted using data from the Shika study, comprising 696 participants with complete information on both single-nucleotide polymorphisms (SNPs) and dietary intake, assessed using the Brief Dietary History Questionnaire (BDHQ). We examined the association of the rs53576 SNP with alcohol and sucrose consumption, as well as with clinical outcomes related to these dietary factors, including liver enzyme levels and liver steatosis. RESULTS: Among individuals with regular alcohol consumption, those with the rs53576 G/G genotype (under a recessive model) exhibited significantly lower alcohol intake (p = 0.002) and higher sucrose intake (p = 0.004) compared to A allele carriers. An association between rs53576 and aspartate aminotransferase (AST) levels, an indicator of alcoholic liver disease (ALD), further supported the relationship between this genotype and alcohol intake. Sex-stratified analysis revealed that the G/G genotype was linked to a greater prevalence of liver steatosis in women, but not in men. Mediation analysis indicated that this association in women was driven by a direct effect independent of sucrose intake volume. CONCLUSIONS: These findings indicate that the OXTR rs53576 polymorphism is associated with distinct alcohol and sucrose intake patterns and susceptibility to liver steatosis, supporting the potential for genotype-informed nutritional interventions aimed at reducing the risk of AUD, ALD, and metabolic dysfunction-associated steatotic liver disease (MASLD). CLINICAL TRIALS REGISTRATION NUMBER AND WEBSITE WHERE IT WAS OBTAINED: This study was approved by the Ethics Committee for Human Studies at Kanazawa University Hospital (1491, 2016-376) and performed following the principles outlined in the Declaration of Helsinki. Network Clinical Trials Registry (UMIN-CTR) under the registration number UMIN000024915. The detailed trial information is available at the following URL: https://center6.umin.ac.jp/cgi-open-bin/icdr/ctr_his_list.cgi?recptno=R000028662.

Although recent studies have reported the association between toxins produced by certain gut microbiota and elevated blood pressure, the relationship between oral frailty (OF) and gut microbiota has rarely been investigated. The purpose of this study was to epidemiologically investigate the relationship between the combination of OF and specific gut microbiota on hypertension in the residents of Shika Town, Ishikawa Prefecture, Japan. A total of 322 residents aged ⩾ 50 years in Shika Town agreed to participate and met the criteria. The OF was evaluated difficulty in chewing and swallowing, oral dryness, number of remaining teeth, and frequency of tooth brushing. Blood pressure was measured using an automatic digital blood pressure meter. Next-generation sequencing was used to analyze the gut microbiota. A two-way analysis of covariance revealed a significant interaction between the two OF groups and the two hypertension groups on Megamonas. The binomial logistic regression analysis stratified by OF revealed a positive correlation between Megamonas and hypertension (OR 1.317; P = 0.023). This cross-sectional epidemiological study of the local residents revealed that the abundance of Megamonas in the OF group was significantly higher in the hypertension group than in the normotension group; however, no such relationship was observed in the non-OF group.

Brain asymmetry is a fundamental feature of neural organization. However, the molecular basis of hippocampal lateralization in response to environmental stimuli remains poorly understood. Here, we examined the transcriptomic profiles of the left and right hippocampal CA1 regions in rats reared under isolated or enriched housing conditions to elucidate hemisphere-specific responses and shared molecular adaptations. RNA-sequencing analysis revealed lateralized differences in the number and identity of differentially expressed genes, accompanied by distinct biological themes, as indicated by overrepresentation and gene set enrichment analysis. The left CA1 region was prominently engaged in pathways related to synaptic organization and mitochondrial function, whereas the right CA1 region exhibited enrichment in transcriptional regulation and RNA metabolic processes. Despite these asymmetries, co-expression and protein–protein interaction network analyses revealed shared molecular architectures. Immediate early genes formed consistent central hubs across both hemispheres, and a common Mecp2–Grin2b–Cdkl5–Tet3 protein interaction cluster was identified as a potential integrative regulatory module. Additional enrichment analysis of differentially expressed genes shared between hemispheres further highlighted conserved responses, particularly in synaptic plasticity and cell–cell communication. Together, these findings demonstrate that the left and right CA1 regions employ distinct yet partially convergent transcriptional programs to adapt to environmental stimuli. This coordinated molecular asymmetry provides novel insights into hippocampal lateralization and its role in experience-dependent brain plasticity.

Background/Objectives: Although tomato consumption has been associated with positive health outcomes, it remains unclear whether it can prevent or exacerbate allergic diseases by regulating eosinophils. We explored the association between dietary tomato intake and blood eosinophil counts in Japanese individuals. Methods: This population-based, cross-sectional study included 1013 participants aged ≥ 40 years. The dietary intake of tomatoes was assessed using a validated, self-administered diet history questionnaire. The peripheral blood eosinophil count was measured, and an elevated blood eosinophil count was defined as a value that exceeded the ≥75th percentile. Results: The mean age of the participants was 62.5 ± 11.2 years, with 474 (46.8%) being male. Overall, 252 participants exhibited elevated blood eosinophil counts (≥204/μL). In the multivariable logistic regression model with adjustment for potential confounders, an increase in tomato intake of 10 g was inversely associated with an elevated blood eosinophil count (odds ratio [OR], 0.895; 95% confidence interval [CI], 0.834–0.961). Except for chronic kidney disease, the baseline participant characteristics did not influence this association. Conclusions: Low dietary tomato intake was associated with an elevated blood eosinophil count in middle-aged and older Japanese individuals. These results may provide insight into the dietary management of eosinophil-related allergic and type 2 inflammatory diseases.

CONTEXT: Selenoprotein P is a hepatokine associated with several metabolic processes. Rs7579 (C > T) is a SeP-related functional single nucleotide polymorphism. OBJECTIVE: In this study, we aimed to identify the environmental factors affecting the relationship between rs7579 and metabolic diseases, such as metabolic dysfunction-associated steatotic liver disease, in the general population. METHODS: This cross-sectional study was based on the Shika Study, a survey of residents in the Noto Peninsula of Ishikawa Prefecture. We analyzed a total of 900 adults, measuring full-length selenoprotein P (FL-SeP) serum levels using a sol-particle homogeneous immunoassay. RESULTS: We observed that selenium and FL-SeP serum levels were associated with dyslipidemia. In males, serum selenium was associated with dyslipidemia and hepatic steatosis. However, in females, FL-SeP tended to be associated with diabetes. Participants carrying the TT genotype and hepatic steatosis exhibited higher levels of liver enzymes, insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), and the homeostasis model assessment of β-cell function than those without hepatic steatosis or with other genotypes. In females carrying the TT genotype of rs7579, hepatic steatosis, hypertension, diabetes, obesity, and metabolic syndrome were associated with higher HOMA-IR levels. CONCLUSION: In this study, we revealed that the association between metabolic diseases and HOMA-IR differed single nucleotide polymorphism genotype and sex dependently. In females carrying the TT genotype of rs7579, hepatic steatosis-associated metabolic disorders (diabetes, hypertension, obesity, and metabolic syndrome) were associated with higher HOMA-IR. The results of this study open the way to genetic signatures-based personalized preventive medicines.