Bone inflammation in postmenopausal women with type 2 diabetes or obesity in relation to Wnt signaling and bone strength.

ShenLingBaiZhu powder ameliorates obesity and atherosclerosis by inhibiting inflammation and apoptosis through the suppression of the TLR4/NF-κB pathway.

Adjunctive use of tirzepatide or semaglutide has demonstrated benefits in improving glucose control (HbA1c, Time in Range), reducing body weight, and insulin requirements, in overweight (OW) or obese (OB) adults with type 1 diabetes (T1D). However, the adverse event (AE) profiles with these agents in this population have not been documented. This study evaluated real-world AEs associated with tirzepatide or semaglutide use in OW/OB adults with T1D. In this single-center study at the Barbara Davis Center for Diabetes, we surveyed 230 adults with T1D who were using tirzepatide or semaglutide as adjunctive therapies. Demographics, data for diabetes control metrics, details of tirzepatide or semaglutide use, and related AEs were collected. Male participants had a higher baseline mean body weight (107.8 ± 18.9 kg vs. 89.6 ± 19.2 kg, P < 0.01) and were older (44.2 ± 12.2 years vs. 40.4 ± 11.5 years, P < 0.05) compared to female participants using tirzepatide or semaglutide at the time of initiation. Symptomatic hypoglycemia was more frequent in the tirzepatide-treated group compared to the semaglutide-treated group (29% vs. 13.4%, P < 0.001). Gastrointestinal AEs did not differ between the two groups. Young adults and females were more likely to report gastrointestinal AEs regardless of the medication. The proportion of individuals who reduced their dose due to AEs was similar. We conclude that symptomatic hypoglycemia was more commonly reported by the tirzepatide-treated group compared to the semaglutide-treated group, while gastrointestinal AEs were comparable between groups. We recommend that individualized risk assessment and close supervision on insulin dose changes are required when prescribing off-label tirzepatide or semaglutide in adults with T1D.

: Introduction Evidence suggests that a low copy number (CN) (2-3) of the α-amylase 1 gene (AMY1) may reduce the risk of dental caries, although findings remain inconsistent. Variations observed between studies could potentially be explained by the modulation of third factors, such as obesity, which may amplify the cariogenic potential of high AMY1 CN. This cross-sectional study explored the relationship between AMY1 gene CN variation (CNV) and dental caries experience, assessed with the Decayed and Filled Surfaces (DFS) index in young adults, and whether this association varied by obesity status. Methods A total of 597 participants (52.4% female, aged 26 - 29 years) from the Norwegian Fit Futures 3 study (2021-2022) were included. Salivary AMY1 CN was measured using droplet digital polymerase chain reaction (ddPCR). Obesity was defined as BMI ≥30 kg/m². We analysed AMY1 CN as both continuous and categorical variables (2-3 (17%), 4-6 (53%), and 7-14 (30%) CN) using logistic regression. Results Although AMY1 CN alone was not associated with DFS, its interaction with obesity was significant (p = 0.036). Among obese individuals, a one-unit increase in AMY1 CN raised the probability of DFS ≥9 by 4.7 percentage points, with no association observed in non-obese individuals. In obese participants (n = 103), sex-adjusted odds ratios (ORs) for DFS ≥9 were as follows: OR 1.25 (95% CI: 1.01-1.53) per unit increase in AMY1 CN; OR 3.47 (95% CI: 1.23-9.79) for 4-6 vs. 2-3 CN, and OR 4.48 (95% CI: 1.35-14.89) for 7-14 vs. 2-3 CN. Conclusion This study found that AMY1 gene CN alone was not directly associated with dental caries in young adults. However, obesity was identified as an effect modifier in the relationship between salivary AMY1 CNV and dental caries experience. Specifically, dental caries experience was higher in obese individuals with above-average AMY1 CN. These findings highlight the complex interplay between genetic, metabolic, and behavioural factors in dental caries development. Further research is needed to confirm these results and to explore the underlying mechanisms of this interaction.

Adult obesity has been linked to specific infections, but evidence across the full spectrum of infectious diseases remains scarce. In this multicohort study with impact modelling, we examined the association between this preventable risk factor and the incidence, hospitalisations, and mortality of 925 bacterial, viral, parasitic, and fungal infectious diseases, and estimated their global and regional attributable impact. We used pooled data from two Finnish cohort studies and repeated analyses in an independent population from the UK Biobank. BMI was assessed at baseline (1998-2002 in the Finnish studies; 2006-10 in UK Biobank), and participants were categorised as having healthy weight (18·5-24·9 kg/m2), overweight (25·0-29·9 kg/m2) or obesity, classified as class I (30·0-34·9 kg/m2), class II (35·0-39·9 kg/m2), or class III (≥40·0 kg/m2). Participants were followed up through national hospitalisation and mortality registries for hospital admissions and deaths due to infectious diseases. Using hazard ratios derived from the Finnish cohorts and UK Biobank, along with obesity prevalence estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study database, we estimated the proportion of fatal infections attributable to obesity globally, regionally, and by country for the years 2018 (before), 2021 (during), and 2023 (after the COVID-19 pandemic). The analysis included 67 766 adults (mean age 42·1 [SD 10·8] years; 49 516 [73·1%] females, 18 250 [26·9%] males) from the Finnish cohorts and 479 498 adults (mean age 57·0 [SD 8·1] years; 261 084 [54·4%] females, 218 414 [45·6%] males) from UK Biobank. Participants had no recent history of infection-related hospitalisations at baseline. During follow-up, there were 8230 incident infection cases in the Finnish cohorts and 81 945 in UK Biobank. Compared with individuals of healthy weight, those with class III obesity had a three-times higher risk of infection-related hospital admissions (Finnish cohorts 2·75 [95% CI 2·24-3·37], UK Biobank 3·07 [2·95-3·19]), death (Finnish cohorts 3·06 [1·25-7·49], UK Biobank 3·54 [3·15-3·98]), or either outcome (Finnish cohorts 2·69 [2·19-3·30], UK Biobank 3·07 [2·95-3·19]). The corresponding pooled hazard ratio for either fatal or non-fatal severe infection among individuals with any obesity (classes I-III) was 1·7 (1·7-1·8). This association was consistent across different indicators of obesity (BMI, waist circumference, and waist-to-height ratio), demographic and clinical subgroups, and a wide range of infections (non-fatal and fatal, acute and chronic, bacterial and viral [including subtypes], and parasitic and fungal). Applying these risk estimates to global burden of disease data, the population attributable fractions of infection-related deaths due to obesity were estimated at 8·6% (6·6-11·1) in 2018, 15·0% (12·8-17·4) in 2021, and 10·8% (8·6-13·6) in 2023. Adult obesity is a risk factor for infection-related hospitalisations and mortality across diverse pathogen types, populations, and baseline clinical profiles, with evidence suggesting that approximately one in ten infection-related deaths worldwide might be attributable to obesity. Wellcome Trust, Medical Research Council, and Research Council of Finland.

BackgroundGrowing evidence suggests positive association between sodium intake and the risk of obesity. Evidence on this topic is lacking from Finland, despite the population's historically high sodium intake and long-standing national salt reduction initiatives.AimsTo examine whether sodium intake and spot urine sodium concentration are associated with general or abdominal obesity in Finnish adults.MethodsWe used cross-sectional, population-based data of the National FinHealth 2017 Study (men=2222, women=2792, ≥18 years-old). Sodium intake was estimated using a validated food frequency questionnaire. A subsample of participants provided spot urine samples (men=558; women=702). General and abdominal obesity were assessed using body mass index and waist circumference. Associations on sex-specific quartiles were examined using multinomial logistic regression, adjusting for key sociodemographic and lifestyle confounders. Spot urine samples were validated against 24-h urine collections.ResultsWomen in the highest quartile of sodium intake had higher odds of general obesity (OR 4.30, 95% CI 2.60-7.12) and abdominal obesity (OR 3.42, 95% CI 2.11-5.56) compared with the lowest quartile. Men in the highest quartile of urine sodium concentration had higher odds of general obesity (OR 6.05, 95% CI 2.83-12.93) and abdominal obesity (OR 4.68, 95% CI 2.44-8.96) compared with the lowest quartile. Spot urine samples showed moderate agreement with 24-h urine collections, with a Spearman's rho of 0.45.ConclusionIn this cross-sectional analysis, higher dietary sodium intake and urine sodium concentration were associated with higher odds of general and abdominal obesity. Prospective studies are needed to confirm causality and to better understand underlying biological mechanisms.

ABSTRACT Aims Metabolic dysfunction‐associated steatotic liver disease (MASLD) is common among morbidly obese patients, but data on non‐invasive tests (NITs)' accuracy for liver fibrosis assessment are limited. We aimed to validate NITs for predicting liver fibrosis and post‐bariatric surgery outcomes. Methods This single‐tertiary‐center retrospective cross‐sectional study with longitudinal follow‐up included morbidly obese adults with biopsy‐proven MASLD undergoing bariatric surgery (laparoscopic Roux‐en‐Y gastric bypass [LRYGB] or laparoscopic sleeve gastrectomy [LSG]) between January 2011 and December 2022. Follow‐up exceeded 1 year. The primary outcome was NITs' performance in predicting liver fibrosis, including liver stiffness measurement (LSM), fibrosis‐4 (FIB‐4), non‐alcoholic fatty liver disease (NAFLD) fibrosis score (NFS), aspartate aminotransferase (AST) to platelet ratio index (APRI), and body mass index (BMI), AST/alanine aminotransferase (ALT) ratio and diabetes (BARD) scores. Secondary outcomes included biochemical and anthropometric changes. Data were compared using χ 2 test, t ‐test, or Wilcoxon tests as appropriate. The predictive performance of NITs was evaluated using receiver‐operating characteristics curve, and changes during follow‐up were assessed with paired tests. Results Among 193 patients (103 [53.4%] female, mean age 36.3 ± 10.9 years, mean BMI 47.70 ± 14.40 kg/m 2 , 78 [40.4%] with diabetes), 58 (30.1%) had liver fibrosis (≥ F1), and 10 (5.2%) had significant fibrosis (≥ F2). NITs showed low diagnostic accuracy for liver fibrosis (area under the receiver‐operating characteristics curve [AUROC]s: LSM 0.38, FIB‐4 0.59, NFS 0.53, APRI 0.50, BARD 0.51). After a median follow‐up of 1.9 years, LSM significantly decreased post‐surgery (7.80 to 5.50 kPa, p &lt; 0.001). APRI and NFS improved (0.21 to 0.18, –0.773 to –1.395, p &lt; 0.001), while FIB‐4 and BARD scores increased (0.52 to 0.60, 2 to 3, p &lt; 0.001) over a median follow‐up of 2.9 years. Anthropometrically, over a median postoperative follow‐up of 2.9 years, BMI decreased significantly (47.70 to 35.05 kg/m 2 , p &lt; 0.001). LRYGB had a higher percentage of total weight loss (%TWL) than LSG (30.8% vs. 28.5%, p = 0.040). Biochemical parameters (AST, ALT, platelets, glycated hemoglobin [HbA1C], low density lipoprotein [LDL]‐cholesterol, and triglycerides) improved significantly post‐surgery (all p &lt; 0.001). Subgroup analysis ( n = 27) showed LSM improvement of &gt; 20% correlated with %TWL &gt; 30% ( p = 0.041). Conclusion Bariatric surgery improved long‐term clinical/biological outcomes, although NITs demonstrated poor diagnostic accuracy for baseline liver fibrosis. Research is needed to assess new NITs for monitoring liver fibrosis in morbidly obese patients.

Cerebrovascular disease (CVD) remains a leading cause of death, with obesity exacerbating stroke risk through multiple metabolic pathways. However, long-term trends in CVD-related mortality among obese adults in the United States remain inadequately defined. We analyzed national mortality data from 1999 to 2020 using the CDC WONDER database. Deaths were included if CVD (ICD-10 I60-I69) was the underlying cause and obesity (E66) a contributing cause. Age-adjusted mortality rates (AAMRs) were calculated, and temporal trends were evaluated using Joinpoint regression to estimate annual percent change (APC) and average annual percent change (AAPC). From 1999 to 2020, 26,410 CVD-related deaths occurred among obese adults. The overall AAMR was 0.53 per 100,000, with an AAPC of 4.59% (95% CI: 3.94 to 5.24). A statistically significant change in trend slope was observed after 2008, with accelerated mortality increases. Females had higher AAMRs (0.56) than males (0.49), though males experienced steeper increases (AAPC 5.98%vs. 3.64%). American Indian/Alaska Native and Black adults had the highest AAMRs (1.11 and 1.01, respectively). Mortality increased in all racial/ethnic groups, most rapidly among White individuals (AAPC 4.66%). Non-metropolitan areas showed higher mortality than metropolitan areas (0.71vs. 0.50), with a widening urban-rural gap. Regionally, the West and Midwest had the highest AAMRs (0.59 and 0.57, respectively). Mortality rose across all age groups, with the steepest increases in younger adults aged 25-54 years. Most deaths occurred in hospitals (56%), followed by home (22.8%) and nursing facilities (15.7%). CVD-related mortality among obese adults has increased significantly since 1999, with substantial disparities across sex, race, geography, and age, highlighting the need for focused public health strategies.

Timing of Energy Intake and Ultra-Processed Food Consumption Are Associated With Obesity in Adults in the United Kingdom: A Pooled Cross-Sectional Analysis of the National Diet and Nutrition Survey (2008-2019).

Single-arm prospective pilot of a 5:2 intermittent fasting regimen supported by meal replacement and digital coaching in adults with obesity.

Challenges and management of obesity in young adults: Perspectives from low and middle-income countries

Fatty liver disease is common among obese individuals and is closely linked to chronic low-grade inflammation. This study examines the relationship between dietary inflammatory index (DII) and serum inflammatory markers in obese individuals with and without non-alcoholic fatty liver disease (NAFLD). In this case-control study, 85 obese adults (BMI ≥ 30), aged 20-70 years, were recruited from two outpatient clinics in Urmia, Iran. NAFLD diagnosis was based on sonography by an endocrinologist. Serum C-reactive protein (CRP) levels were measured using a high-sensitivity immunoturbidimetric assay to assess systemic inflammation. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire (FFQ). The Dietary Inflammatory Index (DII) was calculated to evaluate the inflammatory potential of the diet. Serum CRP levels were significantly higher in the NAFLD group (12.2 mg/L; 95% CI: 9.7-14.7) than controls (8.5 mg/L; 95% CI: 6.0-11.0; p = 0.04). DII scores did not differ significantly between groups (p = 0.2). CRP was positively associated with NAFLD (OR = 2.89; 95% CI: 1.1-7.2), while DII showed no significant association (OR = 0.50; 95% CI: 0.2-1.2). Our findings underscore the role of inflammation in the pathophysiology of fatty liver disease among obese individuals. Elevated CRP levels highlight potential targets for intervention. Although no significant differences in DII were observed, further serum investigation into the relationship between diet, inflammation and fatty liver is warranted.

Background: Obesity is a global health crisis linked to chronic diseases and eating disorders. Rapid eating (characterized by insufficient chewing and rapid swallowing) is believed to contribute to weight gain by weakening satiety signals and increasing calorie consumption; however, evidence in Arab societies remains limited. This study aims to compare chewing and swallowing patterns among obese and non-obese Iraqi adults. It analyzes the relationship between eating speed and body mass index (BMI), appetite, and hunger. It explores gender differences in obesity-related behaviors. Methodology: A cross-sectional study was conducted on 600 Iraqi volunteers (323 males, 277 females), divided into two groups: obese (BMI ≥ 30) and non-obese (BMI = 18.5–24.9). Measurements included: Chewing behavior: average chewing times/mouthful and swallowing time (seconds/mouthful). Appetite and hunger: Likert-type questionnaire (1–10).Anthropometric measurements: height, weight, waist-to-height ratio. Data were analyzed using SPSS (version 26) with t-tests and regression (p &lt; 0.05 statistical significance). Results: Obese individuals showed reduced chewing/bolus and swallowing times compared to non-obese individuals. An inverse relationship was found between chewing/bolus times and body mass index (BMI). Obesity was 36.5% more prevalent among females than males, with a stronger correlation between eating speed and appetite in females (P &lt; 0.05). Chronic diseases (such as diabetes) were more common among obese individuals. Conclusion: Rapid eating patterns (reduced chewing, accelerated swallowing) are strongly associated with higher BMI and appetite disturbances in Iraqi adults. Slowing down eating speed may help promote satiety and weight control, with the need for gender-sensitive interventions, especially for females who are more prone to obesity.

Introduction: anxiety influences the eating behavior of medical students who consume unhealthy foods to mitigate stress by seeking the feeling of well-being and relaxation generated by the release of dopamine associated their consumption. Understanding this relationship is important to design interventions and health programs focused on improving students' well-being and promoting healthier eating habits. And therefore, reduce the recurrence of obesity, diabetes, hypertension, and heart disease in young adults, which promote a greater cardiometabolic risk. Objectives: to determine the level of anxiety in medical students, and its relationship with the consumption of unhealthy foods, obesity, and cardiometabolic risk. Results: 95 % of the students reported symptoms of anxiety (49 % men, 51 % women), with an average of moderate anxiety (p < 0.001); 74 % indicated being emotional eaters (33.87 % men, 40.63 % women), where the most consumed food was sweets (51.4 %), followed by savory foods (32.27 %), fats (11.15 %), and healthy foods (5.18 %). According to the BMI, 44 % of the population is classified as having a high weight (31.87 % overweight and 11.96 % obese), and among this group, 41.5 % have central obesity and are at risk of metabolic disease. Students who exhibited anxiety showed a moderate positive correlation (ρ = 0.497) with the consumption of unhealthy foods, where the exposed group has a high risk of being emotional eaters. Conclusions: the prevalence of anxiety among medical students was high, being this a factor that contributes to the consumption of unhealthy foods, which causes nutritional repercussions and poses a risk for the development of cardiometabolic diseases such as hypertension, diabetes, and dyslipidemias. For this reason, it is important to implement reinforcements and measures in nutritional education, where the scientific and academic community must be included.

Background: Central obesity is strongly associated with insulin resistance and atherogenic dyslipidemia in urban Indian populations. The triglyceride–glucose (TyG) index and its waist-integrated derivative (TyG-WC) have emerged as simple surrogate markers of insulin resistance. Aim of the study was to evaluate the utility of TyGWC index in predicting insulin resistance and central obesity–linked dyslipidemia in a tertiary metabolic clinic setting. Material and Methods: This cross-sectional study included 50 centrally obese adults (waist circumference ≥90 cm in men, ≥80 cm in women). Anthropometric and fasting biochemical parameters (glucose, lipid profile, insulin, HbA1c) were assessed. TyG, TyG-WC, TG/HDL-C ratio, and HOMA-IR were calculated. Correlation and multivariable regression analyses were performed to determine predictors of HOMA-IR. Results: The mean age was 48.6 ± 10.8 years; 56% were male. The mean HOMA-IR was 5.6 ± 2.9, indicating a high prevalence of insulin resistance. TyG-WC showed strong correlation with HOMA-IR (r = 0.74, p &lt; 0.001) and TG/HDL-C ratio (r = 0.81, p &lt; 0.001). In regression analysis, TyG-WC was the strongest independent predictor of HOMA-IR (β = 0.52, p &lt; 0.001), outperforming BMI and age. Conclusion: TyG-WC index is a strong and independent predictor of insulin resistance and central obesity–linked dyslipidemia in urban Indian adults. It represents a simple, inexpensive, and clinically applicable screening tool for identifying high-risk metabolic phenotypes in routine practice.

Peptide YY (PYY), a key satiety hormone, exhibits altered serum concentrations in body weight disorders, although its role remains debated. Conflicting adult studies highlight the need to clarify PYY 1-36 dynamics in pediatric populations with anorexia nervosa (AN) and obesity (OB). Fasting serum PYY 1-36 concentrations were analyzed in 199 girls: 58 with restrictive AN [median age 15.0 (interquartile range; IQR): 14.0-16.0 years], 52 with OB [14.3 (12.3-16.3) years], and 89 healthy controls (C) [16.5 (15.5-17.5) years]. Anthropometric and metabolic/hormonal parameters were assessed. Group differences were evaluated using the Kruskal-Wallis rank-sum test. Relationships between fasting serum peptide YY (PYY) 1-36 concentrations and demographic/clinical parameters were examined using Spearman rank correlation coefficients. AN patients had significantly higher PYY 1-36 levels [77.2 (71.1-82.4) pg/mL] compared to OB [36.0 (34.3-38.5) pg/mL] and C [49.7 (46.7-51.5) pg/mL; p < 0.001]. A strong inverse correlation between PYY and body mass index (BMI) was observed across all subjects (Rho = -0.8, p < 0.001). Receiver operating characteristic (ROC)-derived cut-offs differentiated AN (> 59.04 pg/mL; sensitivity 95%, specificity 100%) and OB (< 43.18 pg/mL; sensitivity 89%, specificity 90%) from C. 1. Our research underscores significant PYY concentration disparities among weight disorders. 2. Significant differences in PYY concentrations in girls with body weight disorders as compared to healthy girls with normal body weight may indicate a role of this peptide in the body's adaptation to maintain energy homeostasis in connection with the ongoing disease.

An expert commission (The Lancet Diabetes & Endocrinology Commission on Clinical Obesity) proposed novel diagnostic criteria distinguishing between preclinical and clinical obesity and suggesting treatment indications for the latter. However, the proportional assignment to preclinical and clinical obesity in adults with BMI-defined obesity, the associated disease risks, as well as the response to lifestyle interventions are not well known. Here we show that among those with BMI-based obesity, 100% are confirmed to have obesity by at least one other anthropometric measure in NHANES 2017-2018 and the prospective EPIC-Potsdam cohort. More than 80% of adults with confirmed obesity meet the criteria for clinical obesity and have 2.8-fold increased risk of incident cardiovascular disease and 7.9-fold increased risk for type 2 diabetes compared to adults without obesity and not fulfilling clinical criteria. Adults with preclinical obesity have no elevated cardiovascular disease risk, but type 2 diabetes risk is markedly increased. A 9-months lifestyle intervention (Tübingen Lifestyle Intervention Programme) decreases the proportionof clinical obesity from 71% to 57%, and that of prediabetes from 52% to 29%.

Incretin-based dual and triple agonists have emerged as effective options for obesity management, offering enhanced weight loss through multi-receptor agonism. However, data on their efficacy and safety remain limited. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of these emerging agents. A comprehensive literature search was conducted using PubMed, the Cochrane Library, and Google Scholar from inception to June 2025 to identify randomized controlled trials evaluating tirzepatide, retatrutide, or mazdutide in obese adults. Clinical outcomes were assessed using the random-effects model and pooled as mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). A total of 10 randomized controlled trials, including 3236 participants, were analyzed. Incretin polyagonists significantly reduced body weight compared to placebo (MD -11.47; 95% CI: -14.00 to -8.95). Significant reductions were also observed in waist circumference (MD -9.40; 95% CI: -11.91 to -6.89), glycated hemoglobin (MD -0.96; 95% CI: -1.16 to -0.75), and fasting plasma glucose (MD -26.89 mg/dL; 95% CI: -33.48 to -20.30). However, the use of dual and triple agonists was associated with a higher risk of any adverse events (AEs) (RR 1.13; 95% CI: 1.08-1.19), including gastrointestinal AEs (nausea, vomiting, diarrhea, constipation), AEs leading to withdrawal (RR 1.96; 95% CI: 1.17-3.30), and hypoglycemic episodes (RR 3.08; 95% CI: 1.61-5.89). No significant difference was found in serious AEs (RR 0.87; 95% CI: 0.65-1.14). In conclusion, incretin-based polyagonists were associated with significant weight reduction and improved metabolic outcomes compared to placebo.

PlanHaSSO: Healthy Habits Plan against Overweight and Obesity. Research project for the development of a protocolized program for primary care

Maternal nutrition during pregnancy critically influences fetal programming, shaping the offspring's lifelong health and disease susceptibility. Both undernutrition and overnutrition affect fetal metabolism, predisposing offspring to obesity and cardiometabolic disorders in adulthood. This review examines current evidence on how maternal nutrition, particularly overnutrition and its complications, such as gestational diabetes mellitus (GDM) and obesity, affects offspring health. It also explores the biochemical and epigenetic mechanisms underlying aberrant fetal programming induced by an unfavorable intrauterine environment. Excess nutrient exposure in utero alters fetal metabolic pathways by modifying the expression of key metabolic genes and nutrient sensors, increasing susceptibility to metabolic syndrome later in life. Maternal obesity has additionally been linked to cognitive dysfunction, immune alterations, and elevated cancer-related mortality in the offspring. GDM exposure disrupts fetal hypothalamic development, impairing appetite regulation. Emerging evidence suggests that epigenetic changes induced by maternal overnutrition may be transmitted across generations and that paternal obesity may also contribute to fetal metabolic programming. Although lifestyle interventions during pregnancy have been tested, they show limited long-term benefits, whereas pre-pregnancy BMI remains the strongest predictor of offspring obesity, emphasizing the critical role of preconception care and the prevention of overweight in women of reproductive age.