Metabolic Syndrome In Offspring Research Articles

Impact of Transgenerational Nutrition on Nonalcoholic Fatty Liver Disease Development: Interplay between Gut Microbiota, Epigenetics and Immunity.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most prevalent pediatric liver disorder, primarily attributed to dietary shifts in recent years. NAFLD is characterized by the accumulation of lipid species in hepatocytes, leading to liver inflammation that can progress to steatohepatitis, fibrosis, and cirrhosis. Risk factors contributing to NAFLD encompass genetic variations and metabolic disorders such as obesity, diabetes, and insulin resistance. Moreover, transgenerational influences, resulting in an imbalance of gut microbial composition, epigenetic modifications, and dysregulated hepatic immune responses in offspring, play a pivotal role in pediatric NAFLD development. Maternal nutrition shapes the profile of microbiota-derived metabolites in offspring, exerting significant influence on immune system regulation and the development of metabolic syndrome in offspring. In this review, we summarize recent evidence elucidating the intricate interplay between gut microbiota, epigenetics, and immunity in fetuses exposed to maternal nutrition, and its impact on the onset of NAFLD in offspring. Furthermore, potential therapeutic strategies targeting this network are also discussed.

Fructooligosaccharides Intake during Pregnancy Improves Metabolic Phenotype of Offspring in High Fat Diet-Induced Obese Mice.

Obesity and metabolic diseases are closely associated, and individuals who become obese are also prone to type 2 diabetes and cardiovascular disorders. Gut microbiota is mediated by diet and can influence host metabolism and the incidence of metabolic disorders. Recent studies have suggested that improving gut microbiota through a fructooligosaccharide (FOS)-supplemented diet may ameliorate obesity and other metabolic disorders. Although accumulating evidence supports the notion of the developmental origins of health and disease, the underlying mechanisms remain obscure. ICR mice are fed AIN-93G formula-based cellulose -, FOS-, acetate-, or propionate-supplemented diets during pregnancy. Offspring are reared by conventional ICR foster mothers for 4 weeks; weaned mice are fed high fat diet for 12 weeks and housed individually. The FOS and propionate offspring contribute to suppressing obesity and improving glucose intolerance. Gut microbial compositions in FOS-fed mothers and their offspring are markedly changed. However, the beneficial effect of FOS diet on the offspring is abolished when antibiotics are administered to pregnant mice. The findings highlight the link between the maternal gut environment and the developmental origin of metabolic syndrome in offspring. These results open novel research avenues into preemptive therapies for metabolic disorders by targeting the maternal gut microbiota.

Impact of cesarean section on metabolic syndrome components in offspring rats.

Epidemiological evidence suggests an association between CS and offspring metabolic syndrome (MetS), but whether a causal relationship exists is unknown. In this study, timed-mated Wistar rat dams were randomly assigned to cesarean section(CS), vaginal delivery (VD), and surrogate groups. The offspring from both CS and VD groups were reared by surrogate dams until weaning, and weaned male offspring from both groups were randomly assigned to receive normal diet (ND) or high-fat/high-fructose diet (HFF) ad libitum for 39 weeks. By the end of study, CS-ND offspring gained 17.8% more weight than VD-ND offspring, while CS-HFF offspring gained 36.4% more weight than VD-HFF offspring. Compared with VD-ND offspring, CS-ND offspring tended to have increased triglycerides (0.27 mmol/l, 95% CI, 0.05 to 0.50), total cholesterol (0.30 mmol/l, -0.08 to 0.68), and fasting plasma glucose (FPG) (0.30 mmol/l, -0.01 to 0.60); more pronounced differences were observed between CS-HFF and VD-HFF offspring in these indicators (triglyceride, 0.66 mmol/l, 0.35 to 0.97; total cholesterol, 0.46 mmol/l, 0.13 to 0.79; and FPG, 0.55 mmol/l, 0.13 to 0.98). CS offspring were more prone to adverse metabolic profile and HFF might exacerbate this condition, indicating the association between CS and MetS is likely to be causal. Whether the observed associations between CS and MetS in non-randomized human studies are causally relevant remains undetermined. Compared with vaginally born offspring rats, CS born offspring gained more body weight and tended to have compromised lipid profiles and abnormal insulin sensitivity, suggesting a causal relationship between CS and MetS that may be further amplified by a high-fat/high-fructose diet. Due to the high prevalence of CS births globally, greater clinical consideration must be given to the potential adverse effects of CS, and whether these risks should be made known to patients in clinical practice merits evaluation.

Dexamethasone exposure during pregnancy triggers metabolic syndrome in offspring via epigenetic alteration of IGF1

BackgroundPrevious research has reported that prenatal exposure to dexamethasone (PDE) results in organ dysplasia and increased disease susceptibility in offspring. This study aimed to investigate the epigenetic mechanism of metabolic syndrome induced by PDE in offspring.MethodsPregnant Wistar rats were administered dexamethasone, and their offspring’s serum and liver tissues were analyzed. The hepatocyte differentiation model was established to unveil the molecular mechanism. Neonatal cord blood samples were collected to validate the phenomenon and mechanism.ResultsThe findings demonstrated that PDE leads to insulin resistance and typical metabolic syndrome traits in adult offspring rats, which originated from fetal liver dysplasia. Additionally, PDE reduced serum corticosterone level and inhibited hepatic insulin-like growth factor 1 (IGF1) signaling in fetal rats. It further revealed that liver dysplasia and functional impairment induced by PDE persist after birth, driven by the continuous downregulation of serum corticosterone and hepatic IGF1 signaling. Both in vitro and in vivo experiments confirmed that low endogenous corticosterone reduces the histone 3 lysine 9 acetylation (H3K27ac) level of IGF1 and its expression by blocking glucocorticoid receptor α, special protein 1, and P300 into the nucleus, resulting in hepatocyte differentiation inhibition and liver dysplasia. Intriguingly, neonatal cord blood samples validated the link between reduced liver function in neonates induced by PDE and decreased serum cortisol and IGF1 levels.ConclusionsThis study demonstrated that low endogenous glucocorticoid level under PDE lead to liver dysplasia by downregulating the H3K27ac level of IGF1 and its expression, ultimately contributing to metabolic syndrome in adult offspring.

Maternal polysorbate 80 intake promotes offspring metabolic syndrome through vertical microbial transmission in mice

Polysorbate 80 (P80) is an emulsifier extensively produced, consumed and discharged into the environment, consequently making human exposure inevitable. Despite evidence suggesting that P80 intake causes metabolic syndrome (MS) in mammals via microbial perturbation, limited data exist on its transgenerational impacts on offspring. In this study, we found that maternal P80 treatment impaired intestinal barrier integrity, leading to metabolic endotoxemia, low-grade inflammation and MS-related symptoms in C57BL/6J female offspring. Further analysis of the gut microbiome revealed MS-related changes in the offspring of P80-treated dams. Fecal microbiota transplantation experiment confirmed the crucial role of the altered microbiome in offspring in the transgenerational impacts of P80. Furthermore, we found that the P80-induced microbial alterations were directly transmitted from P80-treated mothers to their offspring and that interrupting vertical microbial transmission through cesarean section and foster nursing blocked the transgenerational impacts of P80 on the offspring microbiome and metabolic health. Moreover, maternal pectin supplementation also effectively mitigated P80-induced microbial alterations and MS-associated phenotypes in offspring. Together, our results indicated that maternal P80 intake could impair offspring metabolic health through the mother-to-offspring transmission of the microbiome, and maternal pectin supplementation might be a promising strategy for reducing the adverse effects of P80.

P07-067-23 The Effect of Source of Protein Fed During Pregnancy on Development of Characteristics of Metabolic Syndrome in Offspring of Obese Wistar Rats

P07-067-23 The Effect of Source of Protein Fed During Pregnancy on Development of Characteristics of Metabolic Syndrome in Offspring of Obese Wistar Rats

RBM15 suppresses hepatic insulin sensitivity of offspring of gestational diabetes mellitus mice via m6A-mediated regulation of CLDN4

BackgroundGestational diabetes Mellitus (GDM) is a common pregnancy-specific disease with high morbidity, which is linked to a high risk of obesity and diabetes in offspring. N6-methyladenosine modification of RNA is emerging as an important epigenetic mechanism that is widely manifested in many diseases. This study aimed to investigate the mechanism of m6A methylation in metabolic syndrome in offspring result from intrauterine hyperglycemia.MethodsGDM mice were established by feeding a high-fat diet 1 weeks before pregnancy. The m6A RNA methylation quantification kit was used to detect liver tissue methylation levels. PCR array was used to determine the expression of the m6A methylation modification enzyme. Immunohistochemistry, qRT-PCR, and western blot were used to examine the expression of RBM15, METTL13, IGF2BP1, and IGF2BP2. Subsequently, methylated RNA immunoprecipitation sequencing combined with mRNA sequencing, followed by dot blot and glucose uptake tests, were performed.ResultsIn this study, we found that offspring from a GDM mother were more vulnerable to glucose intolerance and insulin resistance. GC–MS revealed significant metabolic changes including saturated fatty acids and unsaturated fatty acids in liver of GDM offspring. We also demonstrated that global mRNA m6A methylation level was significantly increased in the fetal liver of GDM mice, indicating epigenetic change may have a strong relationship with the mechanism of metabolism syndrome. Concordantly, RBM15, the RNA binding methyltransferase, was upregulated in the liver. In vitro, RBM15 suppressed insulin sensitivity and increased insulin resistance through m6A-regulated epigenetic inhabitation of CLDN4. Moreover, MeRIP-sequencing and mRNA-sequencing revealed that differently regulated genes with differential m6A peaks were enriched in metabolic pathways.ConclusionOur study revealed the essential role of RBM15 in insulin resistance and the effect of RBM15-regulated m6A modification in the metabolic syndrome of offspring of GDM mice.

RF22 | PSUN318 Hepatocytes Exposed to PFOA Prior to Differentiation Leads to Epigenetic Changes in Genes Linked With NAFLD

Abstract Background Perfluorooctanoic acid (PFOA), is a persistent fluorinated compound with oil and water repelling properties found in cookware, food packaging and municipal water systems. Adult animals exposed to PFOA develop hepatomegaly, fatty liver, peroxisome proliferation, and immunotoxicity. Rodents exposed to PFOA in utero have altered hepatic lipid metabolism, increased hepatic de novo lipogenesis and susceptibility to non-alcoholic fatty liver disease (NAFLD), but underlying molecular mechanisms remain unknown. With increasing rates of obesity, diabetes, and NAFLD it is critical to examine the mechanisms by which in utero exposure to PFOA contributes to the development of metabolic syndrome in offspring. Objectives To characterize how PFOA exposure during hepatocyte differentiation leads to the development of NAFLD through alterations in DNA methylation profiles and changes in the availability of transcription factor binding sites. Methods HepaRG cells (human-derived hepatocyte progenitor cells) were treated with 0.5uM PFOA or vehicle for 48 hours followed by differentiation. Undifferentiated and differentiated hepatocytes exposed to PFOA were assessed relative to controls (n=4). RNASeq was completed; DESeq2 identified differentially expressed genes via false discovery rate (FDR) of <0.05 after Bonferroni correction. Genome-wide DNA methylation analysis via MethylSeq was completed to identify differentially methylated regions (DMRs) defined as minimum number of CpN =5, absolute change in percent methylation >10%, and FDR of <0.05. Enrichment analysis of transcription factor binding motifs within DMRs and single CpG sites (± 200 bp) was performed using HOMER. Results PFOA treatment resulted in decreased expression of the transcription factors early growth response protein 1 (EGR1), nuclear receptor Nur77 (NR4A1), early growth response protein 2 (EGR2), krueppel-like factor 10 (KLF10) and fos-related antigen 1 (FOSL1), which are key genes linked to impaired hepatic insulin signaling, lipid metabolism, steatosis and fibrosis (q<0.05) in undifferentiated hepatocytes. Differentiated hepatocytes showed decreased expression of peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1α), peroxisome proliferator-activated receptor γ (PPARγ), forkhead box protein O1 (FOXO1) and increased expression of pyruvate dehydrogenase kinase isozyme 4 (PDK4), genes linked to regulation of lipid metabolism and insulin signaling (q <0.05). MethylSeq analysis identified changes in DMRs located in exons, introns, and intergenic regions, with 57 DMRs in undifferentiated hepatocytes (46 with gains; 11 with losses; q <0.05) and 75 DMRs in differentiated hepatocytes (32 with gains; 41 with losses; q<0.05). HOMER identified 29 known transcription factor binding motifs with changes in methylation in undifferentiated hepatocytes (p<0.05) and 19 in differentiated hepatocytes after PFOA treatment (p<0.05), with significant changes in the EGR1 consensus sequence identified in both comparisons. Conclusions We conclude hepatocyte progenitor cells exposed to low dose PFOA results in changes in DNA methylation and expression of key metabolic genes linked to NAFLD, notably EGR1, a gene previously linked to NAFLD, suggesting PFOA exposure in utero has lasting effects. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 12:48 p.m. - 12:53 p.m.

Trimester two gestational exposure to bisphenol A and adherence to mediterranean diet are associated with adolescent offspring oxidative stress and metabolic syndrome risk in a sex-specific manner.

BackgroundExposure to prenatal bisphenol A (BPA) and Mediterranean Diet Score (MDS) has been linked to metabolic risk in child offspring. It remains unclear if independent and interactive effects persist in adolescence.MethodsWe examined prenatal BPA and MDS on adolescent offspring metabolic syndrome risk score (MRS) and 8-isoprostane (8-iso), a biomarker of oxidative stress. Data from maternal-adolescent dyads from a Mexico City cohort were utilized, including trimester-specific prenatal BPA from spot urine and MDS from food frequency questionnaires. Offspring socio-demographic data and biomarkers to estimate MRS and 8-iso were obtained during peri-adolescence.ResultsAdjusted linear regression models examined associations between trimester-specific BPA, MDS, and BPA*MDS on outcomes. Sex-stratified analyses revealed a significant association between MDS with increased 8-iso (β = 0.064, p < 0.05), and a marginal association between trimester two BPA with increased 8-iso (β = 0.237), while MDS modified the marginal association between BPA and 8-iso in females (β = 0.046). A negative, marginal association was observed between trimester two BPA and MRS (β = – 0.728), while BPA * MDS was marginally, positively associated with MRS (β = 0.152) in males.ConclusionsStudy findings indicate that trimester two prenatal BPA and maternal adherence to a Mediterranean diet may have sexually dimorphic effects on adolescent offspring oxidative stress and metabolic syndrome risk.

Maternal Supplementation of Probiotics, Prebiotics or Postbiotics to Prevent Offspring Metabolic Syndrome: The Gap between Preclinical Results and Clinical Translation.

Metabolic syndrome (MetS) is an extremely prevalent complex trait and it can originate in early life. This concept is now being termed the developmental origins of health and disease (DOHaD). Increasing evidence supports that disturbance of gut microbiota influences various risk factors of MetS. The DOHaD theory provides an innovative strategy to prevent MetS through early intervention (i.e., reprogramming). In this review, we summarize the existing literature that supports how environmental cues induced MetS of developmental origins and the interplay between gut microbiota and other fundamental underlying mechanisms. We also present an overview of experimental animal models addressing implementation of gut microbiota-targeted reprogramming interventions to avert the programming of MetS. Even with growing evidence from animal studies supporting the uses of gut microbiota-targeted therapies start before birth to protect against MetS of developmental origins, their effects on pregnant women are still unknown and these results require further clinical translation.

Epigenetic Mediators of Risk for Metabolic Disease Across Generations

Obesity and type 2 diabetes (T2D) are leading global health threats and innovative multi‐pronged approaches are needed to combat both epidemics. Many risk factors for obesity and T2D – beyond genetics – are present before birth, reflecting the influence of environmental factors on germ cells and on the developing infant. For example, parental obesity or diabetes, prenatal undernutrition, and both low and high birth weight, are linked to offspring’s obesity and T2D risk later in life. Such prenatal exposures increase obesity risk not only in the individual exposed to the stressor, but also in their offspring. The result is a vicious cycle of risk to subsequent generations.The concept that the maternal perinatal environment shapes childhood chronic diseases is well‐recognized. However, mounting evidence demonstrates that fathers can also contribute to obesity and diabetes risk to their offspring. While genetic factors are important, additional non‐genetic impacts of paternal metabolism have been demonstrated both in rodent models and in humans. Paternal metabolism can influence epigenetic signals in sperm, including DNA methylation, histone modification, and/or noncoding RNA (ncRNA), which can impact gene expression and development in the offspring. We and others have shown that epigenetic marks are altered in sperm from rodents exposed to prenatal undernutrition, postnatal overnutrition, and other stimuli. While human data are more limited, paternal BMI at the time of conception is associated with infant birth weight and DNA methylation of infant cord blood; differential DNA methylation at some loci persisted to age 7. Our new preliminary data demonstrate that T2D also modifies the sperm methylome.Given that sperm epigenetic marks may be modifiable, this suggests a potential novel approach and untapped opportunity for multigenerational prevention of metabolic disease. We demonstrate that interventions in male mice, including exercise and pharmacological lowering of glucose levels, result in amelioration of obesity, glucose tolerance and metabolic syndrome in offspring.

Development of pups born to rats established as a model of underweight Japanese women and the onset of impaired glucose tolerance

An increasing number of Japanese women of childbearing age are underweight (BMI <18.5), but the association between this and the increased number of low-birth-weight babies born remains unclear. Here, a rat model was established to mimic the undernutrition (85% of the energy required for those with normal activity levels) experienced by such women and to evaluate the associated impaired glucose tolerance. The undernourished Wistar rat group showed increased serum corticosterone level reflecting stress, and greater adrenal weight and size. It also showed greater insulin resistance, higher expression of FOXO-1, a transcription factor related to muscle atrophy, and lower expression of p-Akt, an insulin-dependent signaling factor. Overall, this work shows the key role of undernutrition during pregnancy as a cause of impaired glucose tolerance and increased diabetes risk in offspring. The findings of this study may inform preemptive measures to prevent the development of metabolic syndrome in offspring of undernourished mothers.

Effects of paternal exposure to cigarette smoke on sperm DNA methylation and long-term metabolic syndrome in offspring

BackgroundAlthough paternal exposure to cigarette smoke may contribute to obesity and metabolic syndrome in offspring, the underlying mechanisms remain uncertain.MethodsIn the present study, we analyzed the sperm DNA-methylation profiles in tobacco-smoking normozoospermic (SN) men, non-tobacco-smoking normozoospermic (N) men, and non-smoking oligoasthenozoospermic (OA) men. Using a mouse model, we also analyzed global methylation and differentially methylated regions (DMRs) of the DLK1 gene in paternal spermatozoa and the livers of progeny. In addition, we quantified DLK1 expression, executed an intra-peritoneal glucose tolerance test (IPGTT), measured serum metabolites, and analyzed liver lipid accumulation in the F1 offspring.ResultsGlobal sperm DNA-methylation levels were significantly elevated (p < 0.05) in the SN group, and the methylation patterns were different among N, SN, and OA groups. Importantly, the methylation level of the DLK1 locus (cg11193865) was significantly elevated in the SN group compared to both N and OA groups (p < 0.001). In the mouse model, the group exposed to cigarette smoke extract (CSE) exhibited a significantly higher global methylation DNA level in spermatozoa (p < 0.001) and on the DMR sites of Dlk1 in 10-week-old male offspring (p < 0.05), with a significant increase in Dlk1 expression in their livers (p < 0.001). In addition, IPGTT and LDL levels were significantly altered (p < 0.001), with elevated liver fat accumulation (p < 0.05) in F1 offspring.ConclusionPaternal exposure to cigarette smoke led to increased global methylation of sperm DNA and alterations to the DMR of the DLK1 gene in the F1 generation, which may be inherited parentally and may perturb long-term metabolic function.

PFOA Exposure Prior to Hepatocyte Differentiation Leads to Gene Expression Changes Implicated in Non-Alcoholic Fatty Liver Disease

Background: Perfluorooctanoic acid (PFOA), is a persistent fluorinated compound with oil and water repelling properties found in cookware, food packaging and municipal water systems. Adult animals exposed to PFOA develop hepatomegaly, fatty liver, peroxisome proliferation, and immunotoxicity. Rodents exposed to PFCs in utero have altered hepatic lipid metabolism, increased hepatic de novo lipogenesis and susceptibility to non-alcoholic fatty liver disease (NAFLD), but underlying molecular mechanisms remain unknown. With increasing rates of obesity, diabetes, and NAFLD it is critical to examine the mechanisms by which in utero exposure to PFOA contributes to the development of metabolic syndrome in offspring. Objective: To determine mechanism by which PFOA alters gene expression in undifferentiated hepatic progenitor cells. Design/methods: HepaRG cells, a human derived hepatocyte progenitor cell line, was treated with 0.5uM PFOA or vehicle for 48 hours followed by differentiation into hepatocytes. Total RNA was extracted using the RNeasy (Qiagen) [total RNA A260/280>2 and RNA integrity number >7 (Agilent Bioanalyzer)] to generate libraries with the Illumina TruSeq stranded total RNA kit. RNA-Seq was performed using 85 bp single-end read sequencing to generate >20 million reads per sample. RNAseq data was aligned to hg38 using STAR v2.6.1a and then quantified with featureCounts v1.6.2. DESeq2 identified differentially expressed genes via FDR (false discovery rate) after Bonferroni correction. Differentially expressed gene lists were used for Ingenuity Pathway Analysis (IPA) to identify pathways of biological significance.Results: PFOA treatment resulted in increased expression of transcription factors EGR1 (early growth response protein 1), NR4A1 (nuclear receptor Nur77), EGR2 (early growth response protein 2), KLF10 (Krueppel-like factor 10) and FOSL1 (Fos-related antigen 1), key genes linked to impaired hepatic insulin signaling, hepatic lipid metabolism, steatosis and fibrosis (fold change > 1.5; q <0.05). IPA identified enrichment of canonical pathways with biological relevance including hepatic fibrosis signaling, stellate cell activation, VDR/RXR/TR activation, and Type 2 diabetes mellitus signaling (p<0.01). Conclusion: Hepatocyte progenitor cells exposed to low dose PFOA for 48 hours prior to differentiation results in changes in expression of key metabolic genes linked to the development of NAFLD and enrichment of biologically relevant pathways associated with hepatic fibrosis and hepatocellular carcinoma. These results suggest that PFOA exposure in utero may have lasting effects on hepatic glucose and lipid metabolism after differentiation. Further studies are needed to characterize the longstanding metabolic effects of in utero PFOA exposure in offspring and the mechanisms driving the persistence of these changes.

Prenatal exposure to persistent organic pollutants as a risk factor of offspring metabolic syndrome development during childhood.

Persistent Organic Pollutants (POPs) are exogenous, artificially made chemicals that can disrupt the biological system of individuals and animals. POPs encompass a variety of chemicals including, dioxins, organochlorines (OCs), polychlorinated biphenyl (PCBs), and perfluoroalkyl substances (PFASs) that contain a long half-life and highly resistant to biodegradation. These environmental pollutants accumulate over time in adipose tissues of living organisms and alter various insulin function-related genes. Childhood Metabolic Syndrome (MetS) consists of multiple cardiovascular risk factors, insulin function being one of them. Over the years, the incidence of the syndrome has increased dramatically. It is imperative to explore the role of persistent organic pollutants in the development of Childhood Metabolic Syndrome. Some epidemiological studies have reported an association between prenatal exposure to POPs and offspring MetS development throughout childhood. These findings have been replicated in animal studies in which these pollutants exercise negative health outcomes such as obesity and increased waist circumference. This review discusses the role of prenatal exposure to POPs among offspring who develop MetS in childhood, the latest research on the MetS concept, epidemiological and experimental findings on MetS, and the POPs modes of action. This literature review identified consistent research results on this topic. Even though the studies in this review had many strengths, one major weakness was the usage of different combinations of MetS criteria to measure the outcomes. These findings elucidate the urgent need to solidify the pediatric MetS definition. An accurate definition will permit scientists to measure the MetS as a health outcome properly and allow clinicians to diagnose pediatric MetS and provide individualized treatment appropriately.

Supplemental Berberine in a High-Fat Diet Reduces Adiposity and Cardiac Dysfunction in Offspring of Mouse Dams with Gestational Diabetes Mellitus

There are few evidence-based strategies to attenuate the risk of metabolic syndrome in offspring exposed to gestational diabetes mellitus (GDM). Berberine (BBR) is an isoquinoline alkaloid extracted from Chinese herbs and exhibits glucose lowering properties. We hypothesized that dietary BBR would improve health outcomes in the mouse offspring of GDM dams. Wild-type C57BL/6 female mice were fed either a Lean-inducing low-fat diet (L-LF,10% kcal fat, 35%kcal sucrose) or a GDM-inducing high-fat diet (GDM-HF, 45%kcal fat, 17.5% sucrose) for 6 wk prior to breeding with wild-type C57BL/6 male mice throughout pregnancy and the suckling period. The resulting Lean and GDM-exposed male and female offspring were randomly assigned an LF (10%kcal fat, 35%kcal sucrose), HF (45%kcal fat, 17.5% sucrose), or high-fat berberine (HFB) (45%kcal fat, 17.5% sucrose diet) containing BBR (160mg/kg/d, HFB) at weaning for 12 wk. The main outcome was to evaluate the effects of BBR on obesity, pancreatic islet function, and cardiac contractility in GDM-exposed HF-fed offspring. Significance between measurements was determined using a 2 (gestational exposure) × 3 (diet) factorial design by a 2- way ANOVA using Tukey post-hoc analysis. In the GDM-HF group, body weights were significantly increased (16%) compared with those in baseline (L-LF) animals (P<0.05). Compared with the L-LF animals, the GDM-HF group had a reduction in pancreatic insulin glucose-stimulated insulin secretion (74%) and increased cardiac isovolumetric contraction time (IVCT; ∼150%) (P<0.05). Compared with GDM-HF animals, the GDM-HFB group with the dietary addition of BBR had significantly reduced body weight (16%), increased glucose-stimulated insulin secretion from pancreatic islets (254%), and reduced systolic heart function (46% IVCT) (P<0.05). In a mouse model of GDM, dietary BBR treatment provided protection from obesity and the development of pancreatic islet and cardiac dysfunction.

Metabolic Syndrome in Offspring of Parents with Metabolic Syndrome: A Meta-Analysis

Background: The metabolic syndrome (MetS) represents a clustering of risk factors for cardiovascular diseases that includes abdominal obesity, hypertension, dyslipidemia, and insulin resistance. Objectives: The objective of this study was to reassess the parent-offspring association of MetS since the available findings are still controversial. Methods: The Cochrane Library, PubMed, Embase, and Web of Science databases were searched to identify relevant articles. All studies comparing MetS status between the offspring of parents with MetS and offspring of parents without MetS were included in the analysis. Results: A total of 9 studies met the inclusion criteria and they were analyzed. Offspring of at least 1 parent with MetS had a higher risk of MetS (OR 3.88, 95% CI 2.58–5.83, p < 0.001). Sons and daughters of fathers with MetS both had a higher risk of MetS (OR 2.31, 95% CI 1.70–3.12, p < 0.001, and OR 1.73, 95% CI 1.37–2.18, p < 0.001, respectively). Sons and daughters of mothers with MetS both had a higher risk of MetS (OR 1.95, 95% CI 1.37–2.76, p = 0.0002, and OR 1.91, 95% CI 1.54–2.35, p < 0.001, respectively). Conclusion: This meta-analysis showed that there is a higher risk of MetS in the offspring of parents with MetS. However, there was no differential association of MetS according to gender and/or age of the offspring.

Association Between Maternal Lifestyle and Risk of Metabolic Syndrome in Offspring-A Cross-Sectional Study From China.

BackgroundThe prevalence of MS among children and adolescents continues to rise, which has become an escalating serious health issue worldwide. It had been reported that maternal current lifestyle had a strong independent correlation with offspring health. However, it is not clear whether comprehensive lifestyle of mother has an impact on the MS risk in offspring and the role of offspring’s lifestyle in it.Methods and ResultsWe included 4,837 mother-child pairs from a multi-centered cross-sectional study conducted in China. The information of maternal lifestyle was obtained by self-reported questionnaire, and metabolic syndrome (MS) in offspring was determined by anthropometric measurements and blood tests. Logistic regression models were employed to evaluate the association between maternal lifestyle and risk of MS in offspring. We found maternal healthy lifestyle was independently associated with lower risk of offspring MS, and the risk of MS in offspring decreased with the increased number of maternal ideal lifestyle factors. Although adolescents’ lifestyle did not fully explain the relationship between maternal lifestyle and risk of offspring MS, compared with those had less ideal lifestyle factors in both mothers and offspring, the risk of offspring MS was lower in those had more ideal lifestyle factors in both mothers and adolescents.ConclusionsHealthy lifestyle in mothers was associated with a lower risk of MS in offspring, which was independent of offspring’s lifestyle. These findings support mother-based lifestyle intervention could be an effective strategy to reduce the MS risk in adolescents.

Study of Prevalence of Metabolic Syndrome in Offspring of Type 2 Diabetic Population

Metabolic Syndrome is defined as Syndrome X is a cluster of co-existing metabolic abnormalities likeobesity, hypertension and dyslipidemia leading to a marked increase inDiabetes mellitus and a five fold increase in CVD thereby imposing a great burden on public health andclinical practice. Metabolic syndrome encompasses a set of conditions of which obesity in particularvisceral obesity, is an important component. Obesity has a positive correlation with incidence and severityof diabetes. Aim of the study is to estimate the prevalence of Metabolic syndrome in offspring of Type 2diabetic population. This study was conducted to estimate the prevalence of metabolic syndrome and itscomponents in offsprings of type 2 diabetes Mellitus population and it includes 100 subjects who werediabetic and presenting to Osmania General Hospital, Hyderabad. Offspring of type II diabetes parentsexhibits higher prevalence of metabolic syndrome . Normoglycemic offspring exhibits higher prevalence ofhypertriglyceridemia indicating precedence of lipid abnormalities to glucose intolerance. Diabetic offspringhave a statistically significant prevalence of metabolic syndrome than the non diabetic offspring.

Prenatal low-dose DEHP exposure induces metabolic adaptation and obesity: Role of hepatic thiamine metabolism

Di-(2-ethylhexyl)-phthalate (DEHP) is a ubiquitous environmental pollutant and is widely used in industrial plastics. However, the long-term health implications of prenatal exposure to DEHP remains unclear. We set out to determine whether prenatal DEHP exposure can induce metabolic syndrome in offspring and investigate the underlying mechanisms. A mouse model of prenatal DEHP exposure (0.2, 2, and 20 mg/kg/day) was established to evaluate the long-term metabolic disturbance in offspring. The mice were profiled for the hepatic metabolome, transcriptome and gut microbiota to determine the underlying mechanisms. Thiamine supplementation (50 mg/kg/day) was administered to offspring to investigate the role of thiamine in ameliorating metabolic syndrome. Prenatal exposure to low-dose DEHP (0.2 mg/kg/day) resulted in metabolic syndrome, including abnormal adipogenesis, energy expenditure and glucose metabolism, along with dysbiosis of the gut microbiome, in male offspring. Notably, hepatic thiamine metabolism was disrupted in these offspring due to the dysregulation of thiamine transport enzymes, which caused abnormal glucose metabolism. Prenatal low-dose DEHP exposure caused life-long metabolic consequences in a sex-dependent manner, and these consequences were be attenuated by thiamine supplementation in offspring. Our findings suggest low-dose DEHP exposure during early life stages is a potential risk factor for later obesity and metabolic syndrome.