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Current dietary guidance recommends limiting intakes of saturated fats, but most fails to consider that saturated fats from different food sources may have different health effects.We aimed to evaluate the associations of saturated fats from dairy and nondairy sources with measures of body fat, inflammatory biomarkers, lipid concentrations, and lipid particle sizes and concentrations.The Framingham Offspring Study is a prospective cohort study. Participants (n = 2391) ≥30 y of age who had dietary records and data on the outcomes of interest were included.Among females, those in the highest quintile (compared with the lowest) of dairy-derived saturated fat had lower multivariable-adjusted levels of body fat [BMI (in kg/m2): 26.2 compared with 27.8, P 0.01; and percentage fat mass: 36.7% compared with 38.0%, P = 0.09) and larger LDL particle sizes. Nondairy saturated fat in females was inversely associated with the triglyceride (TG):HDL ratio (P = 0.03). Among males, intakes of dairy-derived saturated fats were inversely associated with C-reactive protein (P 0.01), fibrinogen (P 0.01), TGs (P 0.01), and the TG:HDL ratio (P 0.01). HDL cholesterol was 2.8 mg/dL (P = 0.04) higher among males in the highest (compared with the lowest) quintile of saturated fat from dairy sources. Males with the highest intakes of dairy-derived saturated fats had larger HDL and LDL particle sizes (P 0.01 for both), a higher HDL particle concentration (P 0.01), and a lower VLDL particle concentration (P 0.01). There were no statistically significant adverse effects of saturated fats from nondairy sources on any of these outcomes in either males or females.Males with higher intakes of dairy-derived saturated fats had a less atherogenic profile than males with lower intakes of these fats. These effects were weaker in females. Nondairy saturated fats were not associated with these cardiometabolic outcomes.

Purpose: Stress urinary incontinence (SUI) refers to involuntary leakage from the urethra, synchronous with exertion/effort, sneezing or coughing, which has a negative effect on quality of life. Studies have shown that mild-to-moderate physical activities reduce the risk of SUI by multiple mechanisms. The objective of this study was to determine whether the Rumba dance combined with breathing training (RDBT) can reduce the severity of incontinence and improve the quality of life of patients with SUI. Methods: A randomized clinical trial was conducted with women who were sedentary, were postmenopausal, reported mild-to-moderate SUI on a 1-h pad test, were not already engaged in Rumba dance and did not receive estrogen replacement therapy. The patients were randomly assigned to the RDBT group (n = 13) or the control group (n = 11). The intervention included 90 min of RDBT three times per week for 16 weeks, and the vaginal resting pressure (VRP), pelvic floor muscle (PFM) strength and endurance, 1-h pad test, International Consultation on Incontinence Questionnaire—Urinary Incontinence Short Form (ICIQ—UI SF), and the Incontinence Quality of Life Questionnaire (I—QOL) were measured or completed at baseline and 16 weeks. None of the participants reported adverse events. Results: The mean (±SD) age of the participants was 55.75 ± 5.58 years. After 16 weeks, in the RDBT group, the urine leakage on the 1-h pad test was significantly decreased −2.91 ± 0.49 from the baseline (p = 0.000). The VRP increased from 76.00 ± 16.23 cmH2O to 95.09 ± 18.90 cmH2O (p = 0.000), the PFM endurance of class I (−3.15 ± 1.99% vs. −0.46 ± 0.97%, p = 0.000) and class II (−0.69 ± 0.95% vs. −0.23 ± 0.44%, p = 0.065) increased, and the grades of PFM strength of class I and class II were significantly enhanced (p < 0.01). Finally, the severity of self-reported incontinence (ICIQ—UI SF) significantly decreased from 6.12 ± 2.15 to 3.81 ± 1.68 (p = 0.000), and quality of life (I—QOL) improved from 75.73 ± 11.93 to 83.48 ± 7.88 (p = 0.005). Conclusion: A 16-week RDBT program can increase PFM strength and endurance to reduce the severity of incontinence symptoms and improve the quality of life in patients with SUI, demonstrating the feasibility of recruiting and retaining postmenopausal women with SUI into a RDBT therapeutic program.

Periventricular leukomalacia (PVL) is an essential cause of cerebral palsy in preterm infants, and cystic PVL (cPVL) is the most severe form of the disease. The pathogenesis of cPVL is complex, and immune imbalances and inflammatory responses may play an essential role in it.Peripheral blood from preterm infants with GA32 weeks and BW1,500 g was used in this study and was collected at 34 weeks corrected gestational age and within 24 h after the diagnosis with cranial MRI or cranial ultrasound. The infants were divided into cPVL groups and control groups. Flow cytometry was used to detect peripheral bloodAfter correcting for confounding factors, the proportion of peripheral bloodIt seems that peripheral blood

Protein intake has been shown to lower risk of aging-related functional decline. The goal of this study was to assess long-term effects of weight-adjusted animal (AP) and plant protein (PP) intakes on aging-related change in functional status and grip strength.Framingham Offspring Study participants (n = 1896, 891 men and 1005 women), ≥age 50, were followed for an average of 14.4 years. Protein intake derived from two sets of 3-day diet records (exams 3 and 5) was expressed as both weight-adjusted intake (from residuals) and per kilogram of body weight (g/kg/d). Seven tasks from two standardized assessments (Nagi and the Rosow-Breslau scales) were selected to determine functional status at exams 5-9. Functional impairment was defined as failure to complete (or having a lot of difficulty completing) a given task. Grip strength was assessed by dynamometer at exams 7-9.Participants with higher (vs. lower) weight-adjusted intakes of AP and PP maintained higher functional scores (p = 0.001 and p 0.001, respectively). After accounting for baseline skeletal muscle mass (SMM) and physical activity, only AP was linked with lower risks of functional impairment. Higher AP intake among sedentary individuals led to 29% (95% CI: 0.51-1.00) reduced risks of impairment; among subjects with lower SMM, higher AP was associated with 30% (95% CI: 0.49-0.98) reduced risks. Physical activity and SMM were independently associated with reduced risks of functional impairment, regardless of protein intake. Finally, higher AP intake led to 34% and 48% greater preservation of grip strength in men (p = 0.012) and women (p = 0.034). Results were similar for protein intake expressed as g/kg/d.Higher AP intake and higher levels of physical activity and SMM were independently associated with lower risks of functional impairment and greater preservation of grip strength in adults over the age of 50 years.

Excessive postpartum weight retention puts women at risk for health problems. This study aimed to investigate the effects of dairy foods on weight retention and risk of obesity in postpartum women in the Nurses’ Health Study II. Weight was reported every 2 years. We identified the pre-pregnancy and postpartum exams that were approximately 2 years before and after the birth year. Dairy consumption was averaged during these 4 years. Linear models were used to assess postpartum weight retention. Multivariable models were used to estimate risk of obesity. Women with higher yogurt (≥2 servings/week vs.

We examined the association between potato consumption in two different age periods during adolescence and risk of obesity and cardiometabolic dysfunction in White and Black girls. We used data from the biracial prospective National Growth and Health Study. Average potato consumption was derived from multiple 3-d food records in two age periods, 9–11 and 9–17 years, and included white and sweet potatoes from all sources. Multivariable logistic regression models were used to estimate OR for becoming overweight, developing prehypertension, elevated TAG levels or impaired fasting glucose (IFG) at 18–20 years of age according to the category of daily potato intake. We also stratified by cooking method (fried/non-fried) and race. ANCOVA was also used to estimate adjusted mean levels of BMI, systolic blood pressure, diastolic blood pressure, log-transformed TAG, the TAG:HDL ratio and fasting glucose levels associated with potato intake category. Higher potato consumption was associated with higher fruit and non-starchy vegetable intakes and higher Healthy Eating Index scores in Black girls. There were no statistically significant associations overall between moderate or higher (v. lower) intakes of potatoes and risks of overweight, prehypertension, elevated fasting TAG, high TAG:HDL ratio or IFG. Also, no adverse associations were found between fried or non-fried potato intake and cardiometabolic outcomes. Potato consumption has been the subject of much controversy in recent years. This study adds evidence that potato consumption among healthy girls during the critical period of adolescence was not associated with cardiometabolic risk.

Some studies suggest that dairy foods may be linked with less chronic inflammation. However, few studies have investigated the separate effects of different types of dairy on inflammation. Therefore, the current study aims to examine the separate prospective impacts of milk, yogurt and cheese on biomarkers of chronic inflammation in 1753 community-dwelling participants of the Framingham Offspring Study (FOS). Mean intakes of dairy foods were derived from two sets of three-day diet records. Six inflammatory biomarkers were assessed approximately seven years later at exam 7. Results showed that those who consumed yogurt (vs. those who did not) had statistically significantly lower levels of interleukin-6 (IL-6) (mean log-transformed levels of 1.31 and 1.26 in consumers/non-consumers, respectively, p = 0.02) and fibrin (mean log-transformed levels of 5.91 and 5.89 in consumers/non-consumers, respectively, p = 0.03). The inverse association between IL-6 and yogurt consumption was similar in participants who were of normal weight and those who were overweight. For fibrin, the effects were stronger in overweight individuals. No statistically significant associations were observed between any of these inflammation biomarkers and milk or cheese intakes. Overall, our study compared the separate impacts of three types of dairy foods on chronic inflammation and found that only yogurt intake was linked with lower levels of chronic inflammation.

OBJECTIVES: We examined the prospective association between potato consumption and risk of cardiometabolic disorders including hypertension, high fasting plasma triglycerides, low-density lipoproteins (LDL), and type 2 diabetes mellitus (T2DM) or impaired fasting glucose (IFG) in the prospective Framingham Offspring (FOS) cohort. We also assessed the relationship between fried or non-fried potato consumption and risk of cardiometabolic disorders. METHODS: We included 2549 subjects, aged 30 years old and older. Dietary data were derived from 3-day records from examination visits 3–5. Average consumption of potatoes was classified as

OBJECTIVES: Potatoes are typically considered to be less healthy than most vegetables although the 2015 Dietary Guidelines provide no specific recommendations for intake other than to reduce consumption of fried potatoes. Evidence linking potato consumption, including consumption of fried potatoes with a risk of obesity, is limited. The objective of the current analysis was to study the impact of potato consumption on the risk of obesity and elevated cardiometabolic risk (CMR) in adolescent girls. METHODS: We used data for 2091 girls, ages 9–10 years at enrollment in the prospective National Growth and Health Study (NGHS). and followed for 10 years. Potato consumption was derived from 3-day records collected during the annual follow-up periods. Total potato intake included white and sweet potatoes from all sources including mixed dishes. Total intake was classified as 85% ile of CDC cutoff values); the effects of higher intakes were the same. The odds ratio for elevated blood pressure (≥90th percentile for age, sex, height) associated with moderate (vs. low) intakes of potatoes was 1.16 (95% CI: 0.84–1.59) and again, the effects of higher intakes were very similar. For the relation between potatoes and elevated triglycerides (≥110 mg/dl), the risk was U-shaped with those who had moderate (vs. low) intakes having a 24% lower risk (95% CI: 0.54–1.08). Finally, moderate and higher (vs. lower) potato intakes were linked with non-statistically significant 26% and 30% reduced risks of elevated fasting glucose levels, respectively. CONCLUSIONS: These analyses suggest that there is no adverse effect of moderate daily potato consumption on cardiometabolic risk in adolescent girls. FUNDING SOURCES: The Framingham Heart Study.

OBJECTIVES: Few studies have estimated the independent effects of butter and margarine on risk of cardiovascular disease (CVD). Our goal was to examine these effects as well as that of other fats and oils on risk of CVD and markers of cardiometabolic risk in subjects in the prospective Framingham Offspring Study. METHODS: Data from 2038 adults, who were free of CVD and diabetes through exam 5 were included. Intakes of butter, margarine, mayonnaise, oils, and shortening were assessed using 3-day diet records at exams 3 and 5. Concentrations of low-density lipoproteins (LDL), high-density lipoproteins (HDL), and their particle sizes were analyzed cross-sectionally at exam 5. Subjects were followed from exam 5 to 9 for incident CVD and type 2 diabetes (T2DM) (median follow-up, 16.9 years). Cox proportional hazards models were used to estimate risk of CVD and T2DM and generalized linear models were used to evaluate effects on other cardiometabolic outcomes, while adjusting for age, sex, pack-years of smoking, BMI, physical activity, intakes of other fats, hypertension and use of lipid-lowering medication. Intake of each type of dietary fat was categorized as low, moderate, or high using sensitivity analyses. RESULTS: Intake of >5 g/day of butter (vs. non-consumers) had no effect on CVD risk but was associated with a non-statistically significant 24% lower risk of T2DM. In men, higher butter intake was linked with larger LDL and HDL particles sizes (P 7 g/day (vs. ≤2) of margarine was associated with a 48% (95% CI: 1.03–2.13) increased risk of CVD and a 68% (95% CI: 1.00–2.82) higher risk of T2DM in women. In men, higher margarine intake was associated with much weaker, non-statistically significant increased risks of CVD and T2DM. Finally, total intake of oils (>7 vs. ≤2 g/day) was associated with a strong reduced risk of T2DM (HR: 0.55; 95% CI: 0.36–0.85) in men but not women. There was no effect of margarine or oils on lipid particle sizes in either men or women. CONCLUSIONS: While butter intake had no adverse effect on risk of CVD in either men or women, it was beneficially associated with lipid profiles in men. In women, higher intakes of margarine but not butter were associated with increased risks of both CVD and T2DM. Finally greater oil consumption led to lower risks of T2DM in men. FUNDING SOURCES: NHLBI National Dairy Council.

Introduction: While saturated fat (SFA) intake has long been considered as an important risk factor for cardiovascular disease (CVD), some evidence in recent years has called these findings into question. There is limited evidence examining the separate effects of SFAs from different food sources on cardiovascular risk. Objective: The goal of this study was to determine whether higher (vs. lower) intakes of SFA from dairy and non-dairy sources were associated with risk of incident cardiovascular disease. Methods: Data from 1991 adults, ages 30 and older, who were free of CVD at the time of baseline dietary assessment in the prospective Framingham Offspring Study were included in these analyses. Dairy and non-dairy SFA was assessed using 3-day diet records at exams 3 and 5; intakes were adjusted for body weight using the residual method. Subjects were followed from exam 5 to exam 9 for CVD events (median follow-up 16.9 years). Cox proportional hazards models were used to adjust for confounding by sex, age, BMI, physical activity, smoking (pack-years), non-dairy SFA (in dairy SFA models, and vice versa for non-dairy models), and time dependent occurrence of hypertension or use of lipid-lowering medications. Results: Subjects were classified into 3 categories of sex-specific intake of dairy SFA ( Conclusions: Saturated fats derived from dairy sources were associated with a reduced risk of incident CVD in women. For both men and women, those who had higher intakes of dairy-derived SFA combined with lower intakes of non-dairy SFA tended to have lower risks of CVD than those with lower intakes of SFA from both sources.

Introduction: Diet and exercise are key prevention strategies for type 2 diabetes (T2DM). Few longitudinal studies have examined separate effects of animal and plant proteins on T2DM risk and results are conflicting. The goal of this study was to evaluate the association between usual intake of dietary protein (total, animal, and plant) and T2DM risk. Methods: Data from middle-aged men and women in the longitudinal Framingham Offspring Study (FOS) with approximately 20 years of follow-up were used. Diet was assessed using three-day diet records (exams 3 and 5); protein intake was adjusted for body weight using the residuals from a linear regression model. Glucose was measured after an overnight fast; impaired fasting glucose (IFG) was defined as a FG >100; diabetes was diagnosed using a standardized and validated FOS protocol. To estimate the hazards ratios) (HR) for IFG or T2DM, Cox proportional hazards models were used to adjust for confounding by age, sex, education level, physical activity, cigarette smoking, height, energy intake, and weight-adjusted carbohydrate intake. Results: Subjects with the highest total protein intakes (≥100 g, men, ≥90 g women) had 34% reduced risks of IFG/T2DM (HR: 0.66; 95% CI: 0.51, 0.85). In this cohort, intakes of animal protein were more than double those of plant protein. The highest intakes of animal protein (≥65 g, men; ≥55 g, women) vs. lower intakes ( Conclusions: This prospective study of middle-aged men and women provides important evidence to suggest that dietary protein when combined with an active lifestyle, may be a strategy for lowering long-term risk of diabetes. In this study, animal protein had stronger beneficial effects, but future studies are needed in population groups with higher intakes of plant protein to determine whether these effects would be comparable.

In this study, we sought to investigate the effects of maternal betaine supplementation on the expression and regulation of GALK1 gene in the liver of neonatal piglets. Sixteen sows of two groups were fed control or betaine-supplemented diets (3 g/kg), respectively, throughout the pregnancy. Newborn piglets were individually weighed immediately after birth, and one male piglet close to mean body weight from the same litter was selected and killed before suckling. Serum samples of newborn piglets were analyzed for biochemical indexes, hormone and amino acid levels. Liver samples were analyzed for GALK1 expression by real-time PCR and western blotting, while GALK1 regulational mechanism was analyzed by methylated DNA immunoprecipitation, chromatin immunoprecipitation and microRNAs expression. Betaine-exposed neonatal piglets had lower serum concentration of galactose, which was associated with significantly down-regulated hepatic GALK1 expression. The repression of GALK1 mRNA expression was associated with DNA hypermethylation and more enriched repression histone mark H3K27me3 on its promoter. Binding sites of SP1, GR and STAT3 were predicted on GALK1 promoter, and decreased SP1 protein content and lower SP1 binding to GALK1 promoter were detected in the liver of betaine-exposed piglets. Furthermore, the expression of miRNA-149 targeting GALK1 was up-regulated in the liver of betaine-exposed piglets, along with elevated miRNAs-processing enzymes Dicer and Ago2. Our results suggest that maternal dietary betaine supplementation during gestation suppresses GALK1 expression in the liver of neonatal piglets, which involves complex gene regulation mechanisms including DNA methylation, histone modification, miRNAs expression and SP1-mediated transcriptional modulation.

Introduction: Dietary protein has been shown to prevent age-related functional decline and strength loss, but few studies have examined the separate effects of animal and plant proteins on these outcomes. Hypothesis: We hypothesized that animal protein might provide greater protection against strength loss and functional decline than plant protein in older adults (aged ≥ 50 years) in the Framingham Offspring Study (FOS). Methods: Dietary protein was assessed using 3-day diet records at exams 3 and 5 in the prospective FOS; intakes were adjusted for body weight using the residual method. Functional status scores (median follow-up 17.3 years) was derived from standardized questionnaires at exams 5-9, while grip strength (median follow-up 10.3 years) was measured by hand-held dynamometer at exams 7-9. Multivariable analyses included Cox proportional hazards modeling, repeated-measures mixed models, and analysis of covariance to adjust for sex, age, education, percent of calories from saturated fats, and physical activity. Models for animal protein were adjusted for plant protein intake and vice versa. Results: Subjects were categorized into 3 categories of sex-specific intakes of animal protein ( Conclusions: Higher intakes of both animal and plant protein were protective of self-reported functional status in these analyses while only animal protein was associated with the preservation of grip strength among older adults.

To elucidate the effects of maternal dietary betaine supplementation on hepatic expression of cholesterol metabolic genes in newborn piglets and the involved epigenetic mechanisms, we fed gestational sows with control or betaine-supplemented diets (3 g/kg) throughout pregnancy. Neonatal piglets born to betaine-supplemented sows had higher serum methionine concentration and hepatic content of betaine, which was associated with significantly up-regulated hepatic expression of glycineN-methyltransferase. Prenatal betaine exposure increased hepatic cholesterol content and modified the hepatic expression of cholesterol metabolic genes in neonatal piglets. Sterol regulatory element-binding protein 2 was down-regulated at both mRNA and protein levels, while 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR)was down-regulated at the mRNA level, but up-regulated at the protein level, in betaine-exposed piglets. The transcriptional repression ofHMGCRwas associated with CpG island hypermethylation and higher repressive histone mark H3K27me3 (histone H3 lysine 27 trimethylation) on the promoter, whereas increased HMGCR protein content was associated with significantly decreased expression of miR-497. Furthermore, LDL receptor was significantly down-regulated at both mRNA and protein levels in the liver of betaine-exposed piglets, which was associated with promoter CpG hypermethylation. In addition, the expression of cholesterol-27α-hydroxylase (CYP27α1) was up-regulated at both mRNA and protein levels, while the expression of cholesterol-7α-hydroxylase (CYP7α1) was increased at the mRNA level, but unchanged at the protein level associated with increased expression of miR-181. These results indicate that maternal betaine supplementation increases hepatic cholesterol content in neonatal piglets through epigenetic regulations of cholesterol metabolic genes, which involve alterations in DNA and histone methylation and in the expression of microRNA targeting these genes.

OBJECTIVES: Small dense LDL particles have been shown to promote atherogenic cardiovascular disease (CVD). Dietary fat type may impact LDL particle size, but few studies have examined the association between fatty acid intake and LDL particle size and CVD risk. Our goal was to examine the association of saturated fatty acid (SFA) intake with LDL particle size and CVD risk in subjects in the Framingham Offspring Study (FOS). METHODS: LDL particle profiles were measured by NMR spectroscopic assay during exam visit 4 in the prospective FOS. Dietary fat, carbohydrate and food groups were assessed using 3-day diet records at exams 3 and 5; intakes were adjusted for body weight using the residuals from linear regression models. Multivariable Cox proportional hazards models and generalized linear modeling (GLM) were used to adjust for sex, age, height, pack-years of smoking, fruit and non-starchy vegetable intakes, dairy, LDL particle size, and prevalent hypertension. RESULTS: Subjects were classified into 6 categories using the combined intakes of carbohydrates (

Betaine serves as an animal and human nutrient which has been heavily investigated in glucose and lipid metabolic regulation, yet the underlying mechanisms are still elusive. In this study, feeding sows with betaine-supplemented diets during pregnancy and lactation increased cholesterol content and low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SR-BI) gene expression, but decreasing bile acids content and cholesterol-7a-hydroxylase (CYP7a1) expression in the liver of weaning piglets. This was associated with the significantly elevated serum betaine and methionine levels and hepatic S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) content. Concurrently, the hepatic nuclear transcription factor liver X receptor LXR was downregulated along with activated signal protein AMP-activated protein kinase (AMPK). Moreover, a chromatin immunoprecipitation assay showed lower LXR binding on CYP7a1 gene promoter and more enriched activation histone marker H3K4me3 on LDLR and SR-BI promoters. These results suggest that gestational and lactational betaine supplementation modulates hepatic gene expression involved in cholesterol metabolism via an AMPK/LXR pathway and histone modification in the weaning offspring.

Methyl donors play critical roles in nutritional programming through epigenetic regulation of gene expression. Here we fed gestational sows with control or betaine-supplemented diets (3g/kg) throughout the pregnancy to explore the effects of maternal methyl-donor nutrient on neonatal expression of hepatic lipogenic genes. Betaine-exposed piglets demonstrated significantly lower liver triglyceride content associated with down-regulated hepatic expression of lipogenic genes acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD) and sterol regulatory element-binding protein-1c. Moreover, s-adenosyl methionine to s-adenosyl homocysteine ratio was elevated in the liver of betaine-exposed piglets, which was accompanied by DNA hypermethylation on FAS and SCD gene promoters and more enriched repression histone mark H3K27me3 on SCD gene promoter. Furthermore, glucocorticoid receptor (GR) binding to SCD gene promoter was diminished along with reduced serum cortisol and liver GR protein content in betaine-exposed piglets. GR-mediated SCD gene regulation was confirmed in HepG2 cells in vitro. Dexamethasone (Dex) drastically increased the luciferase activity of porcine SCD promoter, while the deletion of GR response element on SCD promoter significantly attenuated Dex-mediated SCD transactivation. In addition, miR-let-7e, miR-1285 and miR-124a, which respectively target porcine SCD, ACC and GR, were significantly up-regulated in the liver of betaine-exposed piglets, being in accordance with decreased protein content of these three genes. Taken together, our results suggest that maternal dietary betaine supplementation during gestation attenuates hepatic lipogenesis in neonatal piglets via epigenetic and GR-mediated mechanisms.

Betaine, which donates methyl groups through methionine metabolism for DNA and protein methylation, is critical for epigenetic gene regulation, especially during fetal development. Here we fed gestational sows with control or betaine supplemented diets (3 g/kg) throughout the pregnancy to explore the effects of maternal betaine on hepatic cell proliferation in neonatal piglets. Neonatal piglets born to betaine-supplemented sows demonstrated a reduction of cell number and DNA content in the liver, which was associated with significantly down-regulated hepatic expression of cell cycle regulatory genes, cyclin D2 (CCND2) and presenilin1 (PSEN1). Moreover, STAT3 binding to the promoter of CCND2 and PSEN1 was also lower in betaine-exposed piglets, accompanied by strong reduction of STAT3 mRNA and protein expression, along with its phosphorylation at Tyr705 and Ser727 residues. Also, prenatal betaine exposure significantly attenuated upstream kinases of STAT3 signaling pathway (phospho-ERK1/2, phospho-SRC and phospho-JAK2) in the livers of neonates. Furthermore, the repressed STAT3 expression in the liver of betaine-exposed piglets was associated with DNA hypermethylation and more enriched repression histone mark H3K27me3 on its promoter, together with significantly up-regulated expression of H3K27me3 and enhancer of zeste homolog 2 (EZH2) proteins, as well as miR-124a, which targets STAT3. Taken together, our results suggest that maternal dietary betaine supplementation during gestation inhibits hepatic cell proliferation in neonatal piglets, at least partly, through epigenetic regulation of hepatic CCND2 and PSEN1 genes via a STAT3-dependent pathway. These neonatal changes in cell cycle and proliferation regulation may lead to lower liver weight and hepatic DNA content at weaning.