Circadian rhythms regulate sleep, metabolism, and hormone secretion, and their disruption has been linked to increased risk of metabolic disorders. CLOCK variants may relate to disease susceptibility through interactions with behaviors such as sleep duration. We conducted a cross-sectional analysis of 12,092 adults to examine associations between habitual sleep duration, time-restricted eating window (TREW) and common CLOCK single-nucleotide polymorphisms (SNPs) rs1801260 and rs3749474 with metabolic pathologies. Genetic, demographic, and lifestyle data were analyzed using logistic regressions adjusted for age, sex, physical activity and BMI. Sleep duration (<6 h vs. ≥6 h) and TREW (≤8 h/day) were self-reported. TREW of ≤8 h/day was significantly associated with lower odds of obesity (BMI≥30) (OR = 0.88, 95%CI0.75-0.90, p = 2 × 10-5), morbid obesity (BMI≥40) (OR = 0.81, 95%CI:0.67-0.97, p = 0.02), T2DM (OR = 0.81, 95%CI: 0.67-0.99, p = 0.03), and hypertension (HTN) (OR = 0.84, 95%CI:0.75-0.95, p = 0.004). Sleep duration showed a U-shaped association with obesity-related outcomes, with lower odds observed for 6-8 h but no lower odds observed for longer sleep durations. Significant gene-sleep interactions were observed; Among CLOCK rs1801260 GG carriers, sleeping <6 h was associated with higher prediabetes odds compared to ≥6 h (OR = 2.11, 95%CI:1.39-3.18, p = 0.0004). Among CLOCK rs3749474 TT carriers, sleeping <6 h was associated with higher odds for T2DM (OR = 1.70, 95%CI:1.22-2.37, p = 0.004) and for morbid obesity (OR = 1.81, 95%CI:1.34-2.44, p = 9 × 10-5) compared to ≥6 h. In summary, interaction between CLOCK variants and insufficient sleep duration was associated with metabolic outcomes. These findings suggest that sleep duration may be relevant to metabolic risk stratification across CLOCK genotype groups; however, prospective studies are needed to confirm these associations.

Background: The common fat mass and obesity-associated (FTO) gene variant rs9939609 has been linked to elevated risk of obesity and Type 2 diabetes mellitus (T2DM). Eating and sleeping windows gained clinical interest as factors in weight maintenance and have been linked to T2DM risk. Objective: To study the association and interaction between the common FTO rs9939609 variant and eating and sleeping windows to affect T2DM risk in a large community cohort. Methods: This cross-sectional study included 12,254 adult participants. Genetic, anthropometric, and lifestyle behaviors data including eating and fasting windows were analyzed. Logistic and linear regression models, as well as chi-square tests, were applied under additive, dominant, and recessive genetic models (adjusted for age, sex, and BMI). Results: Significant associations between FTO rs9939609 x eating and sleeping window interactions were demonstrated in relation to T2DM risk. Longer eating windows and later last meal timing were associated with an increased risk for T2DM under the additive model (OR = 1.029, 95% CI = 1.002-1.055, and OR = 1.066, 95% CI = 1.012-1.122, respectively), while longer fasting windows were found to be protective under additive model (OR = 0.972, 95% CI = 0.947-0.998). Later bedtime onset was associated with an increased risk for T2DM under additive model (OR = 1.101, 95% CI = 1.005-1.220). Hours of night sleep significantly interacted with FTO rs9939609 under additive genetic model. FTO rs9939609 risk allele carriers with prolonged sleeping windows (OR = 1.137, 95% CI = 1.039-1.354) and poorer sleeping quality (OR = 1.185, 95% CI = 1.038-1.354) had increased risk of T2DM. Conclusions: Eating and fasting windows, late last meal timing, hours of night sleep, late bedtime onset, and poorer sleep quality are significantly associated with T2DM risk among FTO rs9939609 risk carriers and may reflect metabolic vulnerability associated with FTO risk alleles. These findings highlight potential behavioral modification to attenuate genetic risk and provide evidence for actionable prevention strategies in genetically predisposed populations.

ABSTRACT Background Lifestyle factors have been associated with semen quality and have been implicated in the reported global decline in semen parameters. Moderate physical activity has been linked to improved semen quality; however, the association between occupational physical activity and semen quality is limited. Objective To study the association between male occupational physical activity and semen quality parameters. Methods A cross‐sectional single‐center study, with final study cohort of 280 males (after applying inclusion and exclusion criteria on n = 593) attending routine semen analysis at sperm laboratory, was subject to WHO criteria semen quality analysis (semen volume, sperm concentration, total sperm count, percentage sperm motility/morphology) and self‐filled validated physical activity, lifestyle, and demographic questionnaires. Statistical analyses were done using SPSS Statistics (version 23). Results All occupational physical activity characteristics, except for sitting, were significantly associated with semen parameters. Sweating at work and physical tiredness were significantly and negatively associated with multiple semen parameters. Specifically, sweating at work was negatively associated with sperm concentration, morphology, and motility (Spearman r = −0.14 to −0.18, all p < 0.05). Physical tiredness at work was negatively associated with total sperm count, sperm concentration, morphology, and motility (Spearman r = −0.15 to −0.26, all p < 0.05). In hierarchical multiple regression analyses controlling for potential confounders, occupational physical activity expressed as physical tiredness independently predicted lower sperm concentration and morphology ( β = −0.17 and −0.29, respectively; p < 0.01). Discussion Occupational physical activities are negatively associated with semen quality parameters, suggesting a potential adverse effect of work‐related physical exertion on male reproductive function. Conclusions The negative association between occupational physical activity characteristics and semen quality parameters highlights the importance of considering work‐related physical exertion in the context of male fertility assessment, once evidence‐based thresholds and standardized assessment protocols are established.

Background/Objectives: Individual responses to weight-loss diets vary widely due to genetic, metabolic, and lifestyle factors, motivating individualized approaches over "one-size-fits-all" advice. We aimed to evaluate long-term (12-month) weight loss, weight maintenance, and cardiometabolic outcomes of a cohort following a nutrigenetically tailored Mediterranean-style dietary program in a real-world, community setting. Methods: The retrospective data cohort included 426 Israeli adults (mean BMI 32.11 ± 4.58 kg/m2; 66.9% women) who participated in a nutrigenetic weight-loss program. Following nutrigenetic direct-to-consumer screening of 425 genetic variants, the participants received a 3-month personalized adjusted diet with remote dietitian-led follow-up by telephone, after which they transitioned to a 9-month self-monitoring and maintenance period. Blood biochemical parameters were reported from routine Health Maintenance Organization (HMO) laboratory testing. Weight/BMI trajectories (0-3, 3-6, 6-9, 9-12 months) were evaluated using linear mixed-effects models; biomarker changes were analyzed with repeated-measures MANOVA and follow-up univariate ANOVAs. Results: Model-estimated cumulative weight loss at 12 months was 10.12 kg (11.4% of baseline) with a mean BMI reduction of 3.68 kg/m2 (p < 0.001). The steepest decline occurred during months 3-6 (-1.13 kg/month). Triglycerides (-14.06 mg/dL), total cholesterol (-4.68 mg/dL), LDL cholesterol (-2.49 mg/dL), fasting glucose (-5.14 mg/dL), and HbA1c (-0.14%) improved significantly (p < 0.05), while HDL cholesterol levels remained stable (+0.86 mg/dL; p > 0.05) at 12 months. Among participants with elevated baseline biochemical values, levels transitioned to normal range by 12-month follow-up for triglycerides (46.4%), total cholesterol (29.4%), LDL cholesterol (34.5%), glucose (39.6%), and HbA1c (35.5%). Conclusions: In a real-world cohort, inclusion of genetic information to personalize dietary guidance was implemented through a flexible, individually tailored program supported by an initial 3-month phase of remote dietitian-led counseling. This approach was associated with durable, clinically meaningful reductions in weight and cardiometabolic risk markers over 12 months. Randomized trials are warranted to confirm causality and evaluate cost-effectiveness.

BACKGROUND AND AIMS:The functional LDLR rs6511720 polymorphism has been implicated in lipid metabolism and cardiometabolic risk. We aimed to investigate its association with clinically relevant Low-Density Lipoprotein cholesterol (LDL-C) threshold (≥130 mg/dL), cardiometabolic burden, and type 2 diabetes mellitus (T2DM), with emphasis on sex-specific effects. METHODS AND RESULTS:A cross-sectional data analysis was conducted on community-based cohort of 1,442 adults (68.4% females; mean age 58.8 ± 14.0 years). Genotype, anthropometric, biochemical and lifestyle data were collected. Logistic regression analyses were performed under dominant, recessive, and additive genetic models, stratified by sex and adjustment for age, body mass index (BMI) and medications. Cohort genotype frequencies were 8.6% for TT, 18.3% for TG, and 73% for GG. Females T allele carriers were significantly associated with reduced odds of LDL-C ≥130 mg/dL under dominant (OR = 0.72; 95% CI: 0.52-0.98; p = 0.036), and additive (OR = 0.77; 95% CI: 0.62-0.96; p = 0.02) models. Conversely, the G allele was linked to elevated odds of LDL-C ≥130 mg/dL under recessive (OR = 1.40; 95% CI: 1.02-1.91; p = 0.03), and additive (OR = 1.30; 95% CI: 1.04-1.63; p = 0.02) models. The frequency of the GG genotype increased significantly with LDL-C severity, among females with ≥2 cardiometabolic risk factors (p = 0.02). Notably, female T allele carriers (TG + TT) had over twice the odds of T2DM compared to GG homozygotes (10.9% vs. 5.4%; OR = 2.18; 95% CI: 1.28-3.70; p = 0.004). CONCLUSION:LDLR rs6511720 exerts sex-specific pleiotropic effects, with the T allele protective against hypercholesterolemia while associated with increased T2DM susceptibility in females.

Background: The Israeli Mamanet Cachibol League (MCL) is a community-oriented athletic program serving mothers through non-competitive recreational sports participation. This study aimed to assess the effects of the MCL on perceived health status, mental health (happiness, depression, social capital), and healthy lifestyle behaviors (physical activity and nutrition). Methods: This is an experimental study with a sample of 231 women (174 in the experimental group and 57 in the control). Participants completed questionnaires in November 2023 (T1) and then in August 2024 (T2). The questionnaire included questions on sociodemographic characteristics, perceived health status, mental health (happiness, depression, social capital), and healthy lifestyle behaviors (physical activity and nutrition). Results: At T1, the MCL participants reported better mental health (higher subjective happiness and social capital and lower depressive symptoms) than the control group. Over time, participation in the MCL led to significant improvements in mental health (reductions in depression and increases in subjective happiness and social capital). The participants showed substantial improvements in healthy lifestyle behaviors, with moderate effect sizes (effects size > 0.5) observed across these areas. Sociodemographic factors influenced the outcomes, with variations in health perception and physical activity linked to marital status and education level. Conclusions: Participation in the MCL program was associated with better mental health at baseline and significantly improved over time compared to the control group. The MCL participants also showed gains in healthy lifestyle behaviors, highlighting the importance of tailored interventions.

Background/Objective: Dyslipidemia significantly contributes to cardiovascular disease (CVD), with triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) as key components. While genetics play a key role in lipid levels, the interplay between genetic predisposition and modifiable lifestyle factors remains unexplored in population-based studies. We aimed to study the associations between weighted polygenic risk scores (wPRS) for TG and HDL-C, lifestyle, and metabolic factors with lipid traits and CVD. Methods: In this cross-sectional study, genotype, metabolic and lifestyle data from an Israeli cohort (n = 5584 adults) were analyzed. Individual wPRSs were constructed for TG and HDL-C based on SNPs associated with each trait. Gene-environment (lifestyle and metabolic factors) associations were evaluated by stratifying participants into high wPRS (≥90th percentile) vs. lower wPRS (<90th percentile). Results: High wPRSs were significantly associated with unfavorable lipid profiles (higher TG and lower HDL-C) and elevated TG/HDL-C ratios. Males and females in the high wPRSHDL had 97- and 10-fold higher odds of CVD, respectively (p < 0.0001). Individuals with a combined high wPRSHDL and wPRSTG showed a 44-fold increase in CVD odds (p < 0.0001). Obesity (BMI > 30) and HbA1c ≥5.7% were significantly associated with elevated TG and reduced HDL-C levels, particularly in high wPRSHDL and WPRSTG individuals, while moderate wine (1–3 drinks/week) consumption and coffee intake (≥1 cup/day) mitigated these effects, particularly among individuals with high wPRS. Conclusions: Risk stratification based on genetic, lifestyle and metabolic profiles may inform personalized prevention strategies for dyslipidemia.

BackgroundPhysical activity (PA) is a key determinant of women's physical, mental, and social well-being, yet participation in structured sports remains limited due to sociocultural norms, caregiving roles, and accessibility barriers. The Mamanet Cachibol League (Mamanet), a community-based sports initiative in Israel, addresses these barriers by fostering participation among mothers from diverse backgrounds. This study evaluates Mamanet's health and economic impacts among Arab women through a cost–benefit analysis (CBA) and quality-adjusted life year (QALY) framework.MethodsA quantitative pre–post evaluation was conducted with 174 Arab women participating in Mamanet teams across diverse geographic and socioeconomic contexts in Israel. The non-randomized design examined within-participant changes over a 10-month period, providing real-world evidence of programme effectiveness. Participants completed validated Hebrew and Arabic questionnaires before and after the intervention. Health-related variables included self-rated health, psychosomatic symptoms, physical activity, mental well-being, and social capital indicators. The economic evaluation incorporated reductions in healthcare utilization and medication costs, productivity gains, and QALY improvements, accounting for direct and opportunity costs.ResultsMamanet participation was associated with improvements in physical health outcomes, including a significant reduction in psychosomatic symptoms (p < 0.001, effect size = 0.75). Gains in mental well-being were observed but did not reach statistical significance (p = 0.09). Modest increases were found in social capital and community engagement. Economically, participation in the programme was associated with reduced healthcare use, lower absenteeism, and decreased medication expenditures, as well as enhanced productivity. The benefit–cost ratio (BCR) was 1.13, indicating that overall benefits exceeded programme costs.ConclusionThe Mamanet programme yields measurable health, social, and economic benefits for Arab women in Israel, demonstrating how culturally adapted, community-based interventions can reduce barriers to physical activity and promote health equity. Its low-cost, inclusive model offers a scalable framework for integrating women's sports into public health strategies and strengthening community resilience. Beyond Israel, the programme's principles affordability, inclusion, and engagement can inform policies supporting the Sustainable Development Goals (SDG), particularly those addressing gender equality, well-being, and reduced inequalities.

The ketogenic diet (KD) has gained clinical attention for its potential benefits in weight loss and metabolic syndrome. By mimicking fasting through carbohydrate (CHO) restriction, KD shifts energy utilization to ketone bodies (KB) instead of glucose. Despite promising results, the effects on different weight loss indicators remain controversial, with challenges in monitoring adherence standards, optimal macronutrient composition, potential risks, and long-term sustainability. This article aims to review the different weight-loss outcomes of KD interventions for obesity, monitored by KB (adherence indication). Current literature on KD interventions for obesity weight loss monitored by KB show reduction in different outcomes, including body weight, body mass index, waist circumference, visceral adipose tissue, fat mass, and body fat percentage. Minor decreases in lean body mass and skeletal muscle mass were noted without resistance training. Variability existed in adherence (KB markers), CHO intake (7–27

The fields of nutrigenetics and nutrigenomics are rapidly changing our understanding of how individual genetic variations influence the body’s response to nutrients and dietary patterns [...]

Background:Src homology 2 B adaptor protein 1 (SH2B1) gene and variants have been found to be associated with common obesity. We aimed to investigate the association between the common missense variant SH2B1 rs7498665 and common obesity risk as well as interactions with lifestyle variables in an Israeli population. Methods:An adult cohort (n=3,070; ≥18 years) with the SH2B1 rs7498665 variant and lifestyle, behavior (online questionnaire), and blood glucose data was analyzed. Associations between this variant, obesity risk (body mass index [BMI] ≥25 and ≥30 kg/m2), and interactions with behavioral and lifestyle factors (stress levels, eating habits score [EHS], physical activity [PA], and wine consumption) were investigated. Association and gene-environment interactions were analyzed using binary logistic regressions with interaction. Results:SH2B1 rs7498665 carriers were significantly (P<0.05) more likely to be overweight (BMI ≥25 kg/m2) or obese (BMI ≥30 kg/m2) in recessive (odds ratio [OR], 1.90 and 1.36, respectively), additive (OR, 1.24 and 1.14, respectively), and codominant (OR, 2.00 and 1.41, respectively) genetic models. SH2B1 rs7498665 interacted with lifestyle and behavioral factors as well as glucose levels. PA and moderate wine consumption (1 to 3 drinks/week) reduced obesity risk (OR, 0.35 and 0.71, respectively). Conversely, carriers of two risk alleles who reported high stress levels, had ≥median EHS, and who had a fasting glucose level ≥90 mg/dL had a significantly increased obesity risk (OR, 3.63 and 5.82, respectively). Conclusion:Carrying SH2B1 rs7498665 significantly elevates the risk of obesity. Actionable lifestyle and behavioral factors significantly modulate the rs7498665 genetic predisposition to obesity; PA and moderate wine consumption attenuate the risk, while high stress, EHS, and fasting glucose level increase the obesity risk.

Objectives Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder during pregnancy with potential long-term health implications for the mother and child. The interplay between genetics and GDM susceptibility remains an area of active research. Recently, brain-derived neurotrophic factor (BDNF) was investigated in relation to obesity and impaired glucose metabolism and pathogenesis. We aimed to investigate the association of common BDNF polymorphisms, with GDM risk in Israeli females. Methods A cohort of 4,025 Israeli women data for BDNF common SNPs was analyzed for potential association with GDM using binary logistic regressions analysis (SPSS 29.0 and R) adjusted for confounding variables (age, T1DM, T2DM, PCOS) under different genetic models. Results The GDM and Non-GDM genetic frequencies for the BDNF rs925946 Tag-SNP were significantly different. The genetic frequencies were 54.16 %, and 66.91 % for the wild type (GG), 38.88 and 29.64 % for the heterozygotes (TC), and 6.94 and 3.48 % for the risk allele homozygotes (TT) for the GDM non-GDM populations, respectively. Carriers of BDNF rs925946 were significantly associated with higher risk for GDM, following the dominant genetic model (OR=1.7, 95 % CI 1.21-2.39, p=0.002), the recessive genetic model (OR=2.05, 95 % CI 1.04-4.03, p=0.03), and the additive genetic model (OR=1.62, 95 % CI 1.13-2.3, p=0.008). This association persisted after adjusting for age, T1DM, T2DM, and polycystic ovary syndrome (PCOS). Conclusions Carrying BDNF rs925946 polymorphism predisposes to a higher risk of GDM pathogenesis. Its role and implications warrant further investigation, especially when considering preventive measures for GDM development.

Bardet-Biedl syndrome (BBS) is an inherited disorder primarily ciliopathy with pleiotropic multi-systemic phenotypic involvement, including adipose, nerve, retinal, kidney, Etc. Consequently, it is characterized by obesity, cognitive impairment and retinal, kidney and cutaneous abnormalities. Initial studies, including ours have shown that BBS genes play a role in the early developmental stages of adipocytes and β-cells. However, this role in other BBS-related tissues is unknown. We investigated BBS genes involvement in the proliferation and early differentiation of different BBS cell types. The involvement of BBS genes in cellular proliferation were studied in seven in-vitro and transgenic cell models; keratinocytes (hHaCaT) and Ras-transfected keratinocytes (Ras-hHaCaT), neuronal cell lines (hSH-SY5Y and rPC-12), silenced BBS4 neural cell lines (siBbs4 hSH-SY5Y and siBbs4 rPC-12), adipocytes (m3T3L1), and ex-vivo transformed B-cells obtain from BBS4 patients, using molecular and biochemical methodologies. RashHaCaT cells showed an accelerated proliferation rate in parallel to significant reduction in the transcript levels of BBS1, 2, and 4. BBS1, 2, and 4 transcripts linked with hHaCaT cell cycle arrest (G1 phase) using both chemical (CDK4 inhibitor) and serum deprivation methodologies. Adipocyte (m3T3-L1) Bbs1, 2 and 4 transcript levels corresponded to the cell cycle phase (CDK4 inhibitor and serum deprivation). SiBBS4 hSH-SY5Y cells exhibited early cell proliferation and differentiation (wound healing assay) rates. SiBbs4 rPC-12 models exhibited significant proliferation and differentiation rate corresponding to Nestin expression levels. BBS4 patients-transformed B-cells exhibited an accelerated proliferation rate (LPS-induced methodology). In conclusions, the BBS4 gene plays a significant, similar and global role in the cellular proliferation of various BBS related tissues. These results highlight the universal role of the BBS gene in the cell cycle, and further deepen the knowledge of the mechanisms underlying the development of BBS.

Obesity’s variability is significantly influenced by the interplay between genetic and environmental factors. We aimed to integrate the combined impact of genetic risk score (GRSBMI) with physical activity (PA), sugar-sweetened beverages (SSB), wine intake, and eating habits score (EHS) on obesity predisposition risk. Adults’ (n = 5824) data were analyzed for common obesity-related single nucleotide polymorphisms and lifestyle habits. The weighted GRSBMI was constructed and categorized into quartiles (Qs), and the adjusted multivariate logistic regression models examined the association of GRSBMI with obesity (BMI ≥ 30) and lifestyle factors. GRSBMI was significantly associated with obesity risk. Each GRSBMI unit was associated with an increase of 3.06 BMI units (p ≤ 0.0001). PA markedly reduced obesity risk across GRSBMI Qs. Inactive participants’ (≥90 min/week) mean BMI was higher in GRSBMI Q3–Q4 compared to Q1 (p = 0.003 and p < 0.001, respectively). Scoring EHS ≥ median, SSBs (≥1 cup/day), and non-wine drinking were associated with higher BMI within all GRSBMI Qs compared to EHS < median, non-SSBs, and non-wine drinkers. Mean BMI was higher in GRSBMI Q4 compared to other quartiles (p < 0.0001) in non-wine drinkers and compared to Q1 for SSB’s consumers (p = 0.07). A higher GRSBMI augmented the impact of lifestyle factors on obesity. The interplay between GRSBMI and modifiable lifestyle factors provides a tailored personalized prevention and treatment for obesity management.

Purpose This research aimed to characterize the nutritional, health and basic sustainability practices among regular smoothies’ consumers (RSC; ≥ 1-2 servings/week for ≥ 2 months). Design Cross-sectional survey. Setting Self-report online multiple-choice questionnaire survey of random sample of adults from online retailer database and community. Sample 193 healthy Israeli adults (75.6% females, mean age 40.65 ± 14.36) completed an online multiple-choice validated survey from May 2022 to August 2023. Measures Demographic, anthropometric, and lifestyle habits, including physical activity, FV consumption, and sustainability practices. Analysis Data were analyzed using chi-square tests for categorical variables and Mann-Whitney tests for non-normally distributed continuous variables. The level of statistical significance was set at .05. Results RSC were significantly older ( P < .001) and more physically active ( P = .025) than occasional smoothie consumers (OSC). They consumed more FV, reaching nutritional recommendations, and exhibited significant lifestyle changes, including reduced meat ( P = .013) and processed food consumption ( P = .013), and regular meal consumption ( P = .045). RSC used fewer disposables ( P = .002) compared to OSC and non-smoothie consumers ( P = .001). RSC demonstrated a higher incidence of weight reduction compared to weight gain. Conclusion RSC is significantly associated with health and nutritional sustainability.

The global obesity pandemic presents a pressing health challenge, with an increasing prevalence shaped by an intricate interplay of genetics and environment. Brain-derived neurotrophic factor (BDNF) plays a pivotal role in regulating feeding behavior and energy expenditure. BDNF single nucleotide polymorphisms have been linked to obesity risk. We hypothesized that BDNF rs925946 is positively associated with obesity susceptibility in the Israeli population. We aimed to study BDNF rs925946 association with obesity susceptibility and its interaction with environmental factors, including eating habits, sugar-sweetened beverages, and physical activity. A data cohort of 4668 Israeli adults (≥18 years, Jewish) was analyzed. Participants' genotypic data for the BDNF rs925946 and lifestyle and eating behavior questionnaire data were analyzed for the association between obesity predisposition and gene-environment interactions. Female (n = 3259) BDNF rs925946 T-allele carriers had an elevated obesity odd (odds ratio [OR] = 1.2; 95% confidence interval [CI], 1.03-1.4, P = .02). BDNF rs925946 genotype interacted significantly with physical inactivity, sugar-sweetened beverage consumption, and eating habits score to enhance obesity odds (OR = 1.4; 95% CI, 1.14-1.7; OR = 1.54, 95% CI, 1.1-2.15; and OR = 1.4; 95% CI, 1.2-2.11, respectively). Our data demonstrated a significant association between BDNF rs925946 T-allele female carriers and a higher obesity predisposition, affected by modifiable lifestyle factors.

Acute pancreatitis (AP) entails pancreatic inflammation, tissue damage and dysregulated enzyme secretion, including pancreatic lipase (PL). The role of irisin, an anti-inflammatory and anti-apoptotic cytokine, in AP and exocrine pancreatic stress is unclear. We have previously shown that irisin regulates PL through the PPARγ-PGC1α-FNDC5 pathway. In this study, we investigated irisin and irisin’s pathway on AP in in vitro (AR42J-B13) and ex vivo (rat primary acinar) models using molecular, biochemical and immunohistochemistry methodology. Pancreatitis induction (cerulein (cer)) resulted in a significant up-regulation of the PPARγ-PGC1α-FNDC5 axis, PL expression and secretion and endoplasmic reticulum (ER) stress unfolded protein response (UPR) signal-transduction markers (CHOP, XBP-1 and ATF6). Irisin addition in the cer-pancreatitis state resulted in a significant down-regulation of the PPARγ-PGC1α-FNDC5 axis, PPARγ nucleus-translocation and inflammatory state (TNFα and IL-6) in parallel to diminished PL expression and secretion (in vitro and ex vivo models). Irisin addition up-regulated the expression of pro-survival UPR markers (ATF6 and XBP-1) and reduced UPR pro-apoptotic markers (CHOP) under cer-pancreatitis and induced ER stress (tunicamycin), consequently increasing cells viability. Irisin’s pro-survival effect under cer-pancreatitis state was abolished under PPARγ inhibition. Our findings suggest irisin as a potential therapeutic option for AP via its ability to up-regulate pro-survival UPR signals and activate the PPARγ-PGC1α-FNDC5 pathway.

The transmembrane protein 18 (TMEM18) gene plays a central and peripheral role in weight regulation. TMEM18 genetic polymorphisms have been identified as an important risk factor for obesity, depending on ethnic population and age. This research aimed to study the association of common TMEM18 polymorphisms with obesity and their interactions with modifiable factors, namely drinking habits (sugar-sweetened beverages (SSBs), flavored water and wine) and physical activity (PA) in the Israeli population. Adults (n = 3089) were analyzed for common TMEM18 polymorphisms and lifestyle and nutrition habits were obtained from questionnaires using adjusted (age, sex) binary logistic regression models. TMEM18 rs939583 and rs1879523 were significantly associated with increased obesity risk (OR = 1.35, 95% CI (1.17–1.57) and OR = 1.66, 95% CI (1.29–2.15), respectively). TMEM18 rs939583 interacted with consumption of 1–3 weekly glasses of wine and PA to attenuate obesity risk (OR = 0.82 95% CI (0.74–0.9; p < 0.001) and OR = 0.74 95% CI (0.68–0.8), respectively), while physical inactivity, SSBs and flavored water consumption significantly enhanced obesity risk (OR = 1.54 95% CI (1.41–1.67), OR = 1.31 95% CI (1.14–1.51) and OR = 1.35 95% CI (1.13–1.62), respectively). PA duration was significantly associated with a lower BMI for rs939583 risk carriers, with a PA cutoff of >30 min/week (p = 0.005) and >90 min/week (p = 0.01). Common TMEM18 SNPs were significantly linked with adult obesity risk and interacted with modifiable lifestyle factors.