Adult Metabolic Disease Research Articles

Longitudinal evaluation of pediatric and young adult metabolic dysfunction-associated steatotic liver disease defined by MR elastography.

To inform clinical monitoring of children and young adults with metabolic dysfunction-associated steatotic liver disease (MASLD) by characterizing the real-world natural history of MASLD and identifying baseline predictors of liver disease progression. This retrospective study included consecutive patients ages < 23 years with MASLD who underwent serial MR elastography (MRE) and/or MR fat fraction (FF) examinations between 09/2009 and 11/2022. Outcomes of MASLD were defined based on maximum ratio values. A relative change ≥ 19% in liver stiffness measures (LSM) and an absolute change ≥ 5% for liver FF were considered clinically meaningful. Random intercept models characterized the yearly rate of change in LSM (kilopascals per year) and FF (percentage per year). One hundred twenty-one patients (87 males, mean age at baseline: 12 ± 3 [SD] years) underwent 297 MRE examinations. The mean interval between the first and last MRE was 34 (± 24) months (range: 1-120 months). Among the 114 patients with serial LSM, 33% (38/114) showed progression, 46% (53/114) remained stable, and 21% (23/114) showed regression. Among the 88 patients with serial FF measures, 57% (50/88) showed progression, 2% (2/88) remained stable, and 41% (36/88) showed regression. LSM progression was associated with Hispanic ethnicity, baseline BMI-for-age percentile, baseline mean liver FF, and GGT changes over time. Predictors for liver FF progression included ALT, AST, GGT, and LDL. In a real-world sample of children and young adults with MASLD who underwent serial liver MRI, a minority of patients demonstrated improvements in liver stiffness or FF over time. Question In children, there is scarce data regarding the natural history of MASLD. Findings In this retrospective study, most children and young adults with MASLD had either unchanged or worsening liver stiffness (n = 91/114, 79%) and liver fat (n = 52/88, 59%). Clinical relevance Our findings emphasize the need for optimized care in pediatric MASLD. The identified risk factors for the progression of liver fat and stiffness may help to identify children who require interventions beyond changes in lifestyle.

Maternal Broccoli Powder Intake Ameliorates Insulin Resistance and Inflammation via AMPK/mTOR Pathway in the Livers of High-Fructose-Fed Male Rat Offspring Exposed to Maternal Protein Restriction.

Sub-optimal prenatal conditions such as maternal undernutrition during pregnancy and lactation posit high risks of adult metabolic diseases. High fructose intake causes insulin resistance and liver inflammation contributing to metabolic diseases. However, food-based preventive measure for these metabolic diseases in the offspring is under-researched. This study aims to investigate the effect of maternal broccoli powder (BP) intake during lactation on insulin resistance and liver inflammation in high-fructose-diet-fed adult male offspring exposed to maternal protein restriction. Pregnant Wistar rats are provided normal protein (NP) or low protein (LP) diets and 0% or 0.74% BP-containing NP diets and 0% or 0.74% BP-containing LP diet during lactation. At weaning, offspring receiving water (W) or 10% fructose solution (Fr) are assigned into six groups: NP/NP/W, NP/NP/Fr, NP/NPBP/Fr, LP/LP/W, LP/LP/Fr, and LP/LPBP/Fr. At week 13, plasma insulin, macrophage infiltration, activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) phosphorylation, and autophagy flux markers are examined. LP/LPBP/Fr shows lower insulin levels and Homeostatic model assessment for insulin resistance (HOMA-IR) values than LP/LP/Fr. Liver macrophage infiltration are decreased in LP/LPBP/Fr. LP/LPBP/Fr exhibits upregulated AMPK phosphorylation, downregulated mTOR phosphorylation, and increased Microtubule-associated protein1A/1B-light chain 3B-II (LC3B-II) levels. Maternal BP intake during lactation ameliorates insulin resistance and inflammation in the livers of adult offspring on a high-fructose diet from LP mothers.

Socioeconomic disparities in the postnatal growth of preterm infants: a systematic review.

To determine the effect of parental socioeconomic status (SES) on the postnatal growth of preterm infants. A systematic review (PROSPERO registration CRD42020225714) of original articles from Medline, Embase, CINAHL Plus and Web of Science published 1946-2023 was undertaken. Studies were included if they reported anthropometric growth outcomes for preterm infants according to parental SES. Data extraction and assessments of bias and health equity impact were conducted using custom-designed forms. A narrative synthesis of twelve included studies was performed. Most infants were moderate to late preterm. The settings, growth outcomes, timings of growth measurement, and SES measures were heterogenous. Six studies demonstrated an adverse effect of low parental SES on the extrauterine growth of preterm infants, five studies showed no effect, and one study showed a potentially beneficial effect. All studies had a high risk of bias, especially confounding and selection bias. The health equity impact of included studies was largely negative. Limited and low-quality evidence suggests that socioeconomic minoritisation may adversely impact the growth of preterm infants, thereby widening existing socioeconomic health inequities. Observational studies informed by theorisation of the mechanistic pathways linking socioeconomic minoritisation to adverse postnatal growth are required to identify targets for intervention. Limited evidence suggests low parental socioeconomic status (SES) adversely affects the postnatal growth of preterm infants across different settings. Early growth of preterm infants predicts neurodevelopmental outcomes and the risk of cardiovascular and metabolic disease in adulthood. Systematic screening of over 15,000 articles identified only twelve studies which reported postnatal growth outcomes for preterm infants according to parental SES. The health equity impact of the included studies was systematically assessed, and found to be negative overall. This study highlights limitations in existing evidence on the association between parental SES and postnatal growth, and delineates avenues for future research.

Nutrition during Pregnancy: Macronutrient and Specific Needs

Pregnancy is characterized by significant metabolic changes aimed at providing the fetus a regular nutritional intake, adapted to its needs in all circumstances. The nutritional impact on the fetus is assessed by development and growth fetal and by its repercussions on fetal programming which conditions the occurrence of metabolic diseases in adulthood. Maternal weight gain during pregnancy is an important nutritional indicator. Excessive energy intake increases the risk of pregnancy-related high blood pressure, gestational diabetes, macrosomia and dystocia. Insufficient, it exposes to the risk of fetal hypotrophy, morbidity and mortality increase in neonatal and postnatal developmental disorders. Desirable nutritional intakes are close to those recommended in the general population. A debate remains concerning the benefit of systematic supplementation with iron, vitamin D and iodine. It is accepted that a diversified, sufficient and balanced diet is enough to satisfy all needs, with the exception of folic acid, the subdeficiency of which, very common among women of childbearing age, is associated with malformations which can be prevented by systematic supplementation. Others supplementation is only necessary for women at risk.

Nutrition during Pregnancy: Macronutrient and Specific Needs

Pregnancy is characterized by significant metabolic changes aimed at providing the fetus a regular nutritional intake, adapted to its needs in all circumstances. The nutritional impact on the fetus is assessed by development and growth fetal and by its repercussions on fetal programming which conditions the occurrence of metabolic diseases in adulthood. Maternal weight gain during pregnancy is an important nutritional indicator. Excessive energy intake increases the risk of pregnancy-related high blood pressure, gestational diabetes, macrosomia and dystocia. Insufficient, it exposes to the risk of fetal hypotrophy, morbidity and mortality increase in neonatal and postnatal developmental disorders. Desirable nutritional intakes are close to those recommended in the general population. A debate remains concerning the benefit of systematic supplementation with iron, vitamin D and iodine. It is accepted that a diversified, sufficient and balanced diet is enough to satisfy all needs, with the exception of folic acid, the sub-deficiency of which, very common among women of childbearing age, is associated with malformations which can be prevented by systematic supplementation. Others supplementation is only necessary for women at risk.

Salivary biomarkers as assessment of metabolic function and inflammation in children with obesity

Childhood obesity increases adult metabolic and cardiovascular disease risk. Using blood for long-term biomarker analysis in children is problematic because of the discomfort, pain, and anxiety associated with frequent blood draws. Noninvasive methods are vital for predicting childhood obesity complications. This study examined body mass index-for-age percentile scores (zBMI) as a predictor of salivary biomarkers of metabolism and inflammation, including insulin and C-Reactive Protein (CRP), over time. A school sample of 288 adolescents (Mage = 12.1 at study initiation; 46% female; 48% Black, 37% non-Hispanic White, 15% Hispanic or other minorities) were enrolled from greater Birmingham, Alabama. Participants provided salivary samples across four days once per year from 2019–2021. In year 1 of the study, 19% of adolescents were overweight, 18% had obesity, 6.6% had severe obesity, and 7.3% had very severe obesity based on the 2022 CDC Extended BMI-for-Age Growth Charts. Multivariable models showed that lower parental income was associated with an increased risk of obesity (OR = 0.91; 95% CI = 0.85, 0.97; p = 0.009). Greater concentrated poverty, a measure of spatial distribution of socioeconomic deprivation, was associated with an increased risk of severe or very severe obesity (OR = 1.58; 95% CI = 1.01, 2.46; p = 0.043). However, race/ethnicity was not associated with obesity risk. Longitudinal analyses showed that greater zBMI in year 1 was associated with greater salivary CRP ( β = 0.188, SE = 0.058, p = 0.001) and insulin ( β = 0.263, SE = 0.076, p&lt;0.001) in years 2 and 3 of the study after adjusting for year 1 biomarker levels, sex, race/ethnicity, and concentrated poverty. Multivariable models indicated that an accelerated increase in zBMI/year was associated with an accelerated increase in CRP/year ( β = 0.119, SE = 0.048, p = 0.014), but there was no association between the rates of change in zBMI and insulin. Future analyses will incorporate additional hormones, such as adiponectin, and inflammatory cytokines measured in saliva. In conclusion, these results indicate that salivary biomarkers can capture physiological differences associated with zBMI in school-age children. Saliva may constitute a useful non-invasive tool for evaluating markers of inflammation and/or metabolism related to zBMI in children outside clinical settings. This research was supported by an Institute of Education Sciences, U.S. Department of Education Grant (R305A180074) to SM and RE and a National Heart, Lung, and Blood Institute K99R00 Grant (1K99HL165091-01A1) to KMK. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The association between plasma angiopoietin-like protein 4, glucose and lipid metabolism during pregnancy, placental function, and risk of delivering large-for-gestational-age neonates

BackgroundLarge-for-gestational-age (LGA) neonates have increased risk of adverse pregnancy outcomes and adult metabolic diseases. We aimed to investigate the relationship between plasma angiopoietin-like protein 4 (ANGPTL4), a protein involved in lipid and glucose metabolism during pregnancy, placental function, growth factors, and the risk of LGA. MethodsWe conducted a prospective cohort study and recruited women with singleton pregnancies at the National Taiwan University Hospital between 2013 and 2018. First trimester maternal plasma ANGPTL4 concentrations were measured. ResultsAmong 353 pregnant women recruited, the LGA group had higher first trimester plasma ANGPTL4 concentrations than the appropriate-for-gestational-age group. Plasma ANGPTL4 was associated with hemoglobin A1c, post-load plasma glucose, plasma triglyceride, plasma free fatty acid concentrations, plasma growth hormone variant (GH-V), and birth weight, but was not associated with cord blood growth factors. After adjusting for age, body mass index, hemoglobin A1c, and plasma triglyceride concentrations, plasma ANGPTL4 concentrations were significantly associated with LGA risk, and its predictive performance, as measured by the area under the receiver operating characteristic curve, outperformed traditional risk factors for LGA. ConclusionsPlasma ANGPTL4 is associated with glucose and lipid metabolism during pregnancy, plasma GH-V, and birth weight, and is an early biomarker for predicting the risk of LGA.

Selenium supplementation via modulation of selenoproteins ameliorates binge drinking-induced oxidative, energetic, metabolic, and endocrine imbalance in adolescent rats' skeletal muscle.

Adolescence is characterized by increased vulnerability to addiction and ethanol (EtOH) toxicity, particularly through binge drinking (BD), a favored acute EtOH-ingestion pattern among teenagers. BD, highly pro-oxidant, induces oxidative stress (OS), affecting skeletal muscle (SKM), where selenium (Se), an antioxidant element and catalytic center of selenoproteins, is stored, among other tissues. Investigating the effects of Se supplementation on SKM after BD exposure holds therapeutic promise. For this, we randomised 32 adolescent Wistar rats into 4 groups, exposed or not to intermittent i.p. BD [BD and control (C)] (3 g EtOH per kg per day), and supplemented with selenite [BDSe and CSe] (0.4 ppm). In SKM, we examined the oxidative balance, energy status (AMPK, SIRT-1), protein turnover (IRS-1, Akt1, mTOR, IGF-1, NF-κB p65, MAFbx, ULK1, pelF2α), serum myokines (myostatin, IL-6, FGF21, irisin, BDNF, IL-15, fractalkine, FSTL-1, FABP-3), and selenoproteins (GPx1, GPx4, SelM, SelP). In the pancreas, we studied the oxidative balance and SIRT-1 expression. Selenite supplementation mitigated BD-induced OS by enhancing the expression of selenoproteins, which restored oxidative balance, notably stimulating protein synthesis and normalizing the myokine profile, leading to improved SKM mass growth and metabolism, and reduced inflammation and apoptosis (caspase-3). Selenite restoration of SelP's receptor LRP1 expression, reduced by BD, outlines the crucial role of SKM in the SelP cycle, linking Se levels to SKM development. Furthermore, Se attenuated pancreatic OS, preserving insulin secretion. Se supplementation shows potential for alleviating SKM damage from BD, with additional beneficial endocrine effects on the pancreas, adipose tissue, liver, heart and brain that position it as a broad-spectrum treatment for adolescent alcohol consumption, preventing metabolic diseases in adulthood.

The influence of maternal diet on offspring's gut microbiota in early life.

The influence of maternal diet on offspring's health is an area of study that is linked to epigenetics. Maternal diet contributes to determining the health status of offspring and maternally linked mechanisms and is a global health challenge that requires attention. The impact of gut microbiota on host metabolism and offspring health is still not established. In this review, we intend to discuss the evidence on the impact of maternal diet and the health of offspring gut microbiota. The paper focuses on the gut microbiome of animal models. It captures the maternal diet and its influence on the offspring's gut microbiota, behavior that is supported by cell experimental results. Both inflammation and immune status of offspring induced by maternal diet are discussed. Finally, this review used predicted biological pathways involved inmaternal diet and offspring health, and the influence of maternal diet on gut microbiota and offspring behavior. Obesity, diabetes, asthma and allergies, and neurodegenerative disorders and prospects for maternal diet, and microbiota and offspring health were discussed. The review was able to gather that a high-fat diet during pregnancy created a long-lasting metabolic signature on the infant's innate immune system, altering inflammation in the offspring microbiota, which predisposed offspring to obesity and metabolic diseases in adulthood.

Diagnostic accuracy and the first genotype-phenotype correlation in glycogen storage disease type V.

Glycogen storage disease type V (GSDV) is an autosomal recessive metabolic condition caused by pathogenic PYGM variants. This is an underdiagnosed condition as it presents with exercise intolerance in children. We reviewed the GSDV cases of a tertiary hospital center to assess diagnostic timing/accuracy, as well as potential clinical/analytical predictors of such factors. We retrospectively reviewed all GSDV cases with follow-up in both Pediatric and Adult Metabolic Diseases consultations. We included 28 cases and assessed their hospital record for clinical information. Over 90% of our cases had late diagnoses, with more than 50% being diagnosed in adulthood despite symptom onset in preschool (very late diagnosis). Diagnostic age was lower in patients exhibiting myoglobinuria. Interestingly, patients with a positive family history of GSDV had similar rates of very late diagnoses, likely since the index case was already detected very late in life. Finally, we observe that the R50* variant is associated with increased myoglobinuria and CK elevation, in a dosage-dependent manner. We concluded that GSDV is severely underdiagnosed, and that some clinical and analytical aspects of the condition can be more indicative of this diagnosis. Furthermore, we propose for the first time a genotype-phenotype correlation in GSDV. GSDV is a pediatric-onset metabolic disorder that is mostly diagnosed late in the adult age and commonly misdiagnosed. We observed the first genotype-phenotype correlation in GSDV, regarding the common R50* variant. Awareness of GSDV for pediatricians and the overall medical community is vital.

Gestational exposure to bisphenol S induces microvesicular steatosis in male rat offspring by modulating metaflammation

Prenatal exposure to endocrine-disrupting bisphenol A (BPA) shows a long-lasting programming effect on an organ's metabolic function and predisposes it to the risk of adult metabolic diseases. Although a reduced contaminant risk due to “BPA-free” exposure is proposed, limited data on a comparative assessment of gestational exposure to BPS and BPA and their effects on metaflammation in predisposing liver metabolic disease is reported. Pregnant Wistar rats were exposed to BPS and BPA (0.0, 0.4, 4.0 μg/kg bw) via gavage from gestational day 4 to 21, and effects were assessed in the 90 d male offspring. Prenatal BPS-exposed offspring showed a more obesogenic effect than BPA, including changes in body fat distribution, feed efficiency, and leptin signalling. The BPS exposure induced the adipocyte hypertrophy of visceral adipose to a greater extent than BPA. The adipose hypertrophy was augmented by tissue inflammation, endoplasmic reticulum (ER) stress, and apoptosis due to increased expression of pro-inflammatory (IL6, IL1β, CRP, COX2) cytokines, ER stress modulator (CHOP), and apoptotic effector (Caspase 3). The enlarged, stressed, inflamed adipocytes triggered de novo lipogenesis in the bisphenol-exposed offspring liver due to increased expression of cholesterol and lipid biogenesis mediators (srebf1, fasn, acaca, PPARα) concomitant with elevated triacylglycerol (TG) and cholesterol (TC), resulted in impaired hepatic clearance of lipids. The lipogenic effects were also promoted by increased expression of HSD11β1. BPS exposure increased absolute liver weight, discoloration, altered liver lobes more than in BPA. Liver histology showed numerous lipid droplets, and hepatocyte ballooning, upregulated ADRP expression, an increased expression of pro-inflammatory mediators (IL6, CRP, IL1β, TNFα, COX2), enhanced lipid peroxidation in the BPS-exposed offspring's liver suggest altered metaflammation leads to microvesicular steatosis. Overall, gestational BPS exposure demonstrated a higher disruption in metabolic changes than BPA, involving excess adiposity, liver fat, inflammation, and predisposition to steatosis in the adult male offspring.

Automated body composition estimation from device-agnostic 3D optical scans in pediatric populations

Excess adiposity in children is strongly correlated with obesity-related metabolic disease in adulthood, including diabetes, cardiovascular disease, and 13 types of cancer. Despite the many long-term health risks of childhood obesity, body mass index (BMI) Z-score is typically the only adiposity marker used in pediatric studies and clinical applications. The effects of regional adiposity are not captured in a single scalar measurement, and their effects on short- and long-term metabolic health are largely unknown. However, clinicians and researchers rarely deploy gold-standard methods for measuring compartmental fat such as magnetic resonance imaging (MRI) and dual X-ray absorptiometry (DXA) on children and adolescents due to cost or radiation concerns. Three-dimensional optical (3DO) scans are relatively inexpensive to obtain and use non-invasive and radiation-free imaging techniques to capture the external surface geometry of a patient's body. This 3D shape contains cues about the body composition that can be learned from a structured correlation between 3D body shape parameters and reference DXA scans obtained on a sample population. This study seeks to introduce a radiation-free, automated 3D optical imaging solution for monitoring body shape and composition in children aged 5-17. We introduce an automated, linear learning method to predict total and regional body composition of children aged 5-17 from 3DO scans. We collected 145 male and 206 female 3DO scans on children between the ages of 5 and 17 with three scanners from independent manufacturers. We used an automated shape templating method first introduced on an adult population to fit a topologically consistent 60,000 vertex (60k) mesh to 3DO scans of arbitrary scanning source and mesh topology. We constructed a parameterized body shape space using principal component analysis (PCA) and estimated a regression matrix between the shape parameters and their associated DXA measurements. We automatically fit scans of 30 male and 38 female participants from a held-out test set and predicted 12 body composition measurements. The coefficient of determination (R2) between 3DO predicted body composition and DXA measurements was at least 0.85 for all measurements with the exception of visceral fat on 3D scan predictions. Precision error was 1-4 times larger than that of DXA. No predicted variable was significantly different from DXA measurement except for male trunk lean mass. Optical imaging can quickly, safely, and inexpensively estimate regional body composition in children aged 5-17. Frequent repeat measurements can be taken to chart changes in body adiposity over time without risk of radiation overexposure.

Exercise intervention during pregnancy induces DNA methylation alterations in maternal blood and cord blood.

Exercise intervention during pregnancy induces DNA methylation alterations in maternal blood and cord blood.

Effect of foetal exposure to famine on the risk of nonalcoholic fatty liver disease in adulthood: A systematic review and meta-analysis.

The risk of metabolic disease in adulthood is not only attributed to an unhealthy lifestyle after birth but also to famine exposure during the foetal period. This systematic review and meta-analysis aimed to evaluate the effects of foetal exposure to famine as a risk factor for developing nonalcoholic fatty liver disease (NAFLD) in adulthood. Studies were retrieved from PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases to evaluate the effect of foetal exposure to famine on the risk of nonalcoholic fatty liver disease in adulthood. Six studies involving 90,582 subjects were included in this meta-analysis. Foetal exposure to famine was associated with an increased risk of NAFLD(RR=1.17, 95% CI: 1.08-1.27, P < 0.0001). Exposure to famine during the foetal period significantly increased the incidence of NAFLD in women (RR=1.27, 95% CI: 1.16-1.40, P <0.00001), while similar results were not observed in the male subgroup (RR =0.99, 95% CI: 0.89-1.11, P=0.88). Foetal exposure to famine was associated with the risk of mild NAFLD (RR=1.17, 95% CI: 1.02-1.33, P=0.02) and moderate to severe NAFLD (RR=1.51, 95% CI: 1.16-1.98, P=0.002). Foetal exposure to famine is associated with an increased risk of NAFLD in adulthood. Women with NAFLD and moderate to severe NAFLD have a more robust association with foetal exposure to famine.

Neonatal hyperoxia leads to white adipose tissue remodeling and susceptibility to hypercaloric diet

AbstractIndividuals born preterm are at higher risk of cardiovascular and metabolic diseases in adulthood, through mechanisms not completely understood. White adipose tissue in humans and rodents is a dynamic endocrine organ and a critical player in the regulation of metabolic homeostasis. However, the impact of preterm birth on white adipose tissue remains unknown. Using a well‐established rodent model of preterm birth‐related conditions in which newborn rats are exposed during postnatal days 3–10 to 80% of oxygen, we evaluated the impact of transient neonatal hyperoxia on adult perirenal white adipose tissue (pWAT) and liver. We further assessed the effect of a second hit with a high‐fat high‐fructose hypercaloric diet (HFFD). We evaluated 4‐month‐old adult male rats after 2 months of HFFD. Neonatal hyperoxia led to pWAT fibrosis and macrophage infiltration without modification in body weight, pWAT weight, or adipocyte size. In animals exposed to neonatal hyperoxia vs. room air control, HFFD resulted in adipocyte hypertrophy, lipid accumulation in the liver, and increased circulating triglycerides. Overall, preterm birth‐related conditions had long‐lasting effects on the composition and morphology of pWAT, along with a higher susceptibility to the deleterious impact of a hypercaloric diet. These changes suggest a developmental pathway to long‐term metabolic risk factors observed clinically in adults born preterm through programming of white adipose tissue.

Programming of metabolism by adipokines during development.

The intrauterine and early postnatal periods represent key developmental stages in which an organism is highly susceptible to being permanently influenced by maternal factors and nutritional status. Strong evidence indicates that either undernutrition or overnutrition during development can predispose individuals to disease later in life, especially type 2 diabetes mellitus and obesity, aconcept known as metabolic programming. Adipose tissue produces important signalling molecules that control energy and glucose homeostasis, including leptin and adiponectin. In addition to their well-characterized metabolic effects in adults, adipokines have been associated with metabolic programming by affecting different aspects of development. Therefore, alterations in the secretion or signalling of adipokines, caused by nutritional insults in early life, might lead to metabolic diseases in adulthood. This Review summarizes and discusses the potential role of several adipokines in inducing metabolic programming through their effects during development. The identification of the endocrine factors that act in early life to permanently influence metabolism represents a key step in understanding the mechanisms behind metabolic programming. Thus, future strategies aiming to prevent and treat these metabolic diseases can be designed, taking into consideration the relationship between adipokines and the developmental origins of health and disease.

Exposure to Obesogenic Environments during Perinatal Development Modulates Offspring Energy Balance Pathways in Adipose Tissue and Liver of Rodent Models

Obesogenic environments such as Westernized diets, overnutrition, and exposure to glycation during gestation and lactation can alter peripheral neuroendocrine factors in offspring, predisposing for metabolic diseases in adulthood. Thus, we hypothesized that exposure to obesogenic environments during the perinatal period reprograms offspring energy balance mechanisms. Four rat obesogenic models were studied: maternal diet-induced obesity (DIO); early-life obesity induced by postnatal overfeeding; maternal glycation; and postnatal overfeeding combined with maternal glycation. Metabolic parameters, energy expenditure, and storage pathways in visceral adipose tissue (VAT) and the liver were analyzed. Maternal DIO increased VAT lipogenic [NPY receptor-1 (NPY1R), NPY receptor-2 (NPY2R), and ghrelin receptor], but also lipolytic/catabolic mechanisms [dopamine-1 receptor (D1R) and p-AMP-activated protein kinase (AMPK)] in male offspring, while reducing NPY1R in females. Postnatally overfed male animals only exhibited higher NPY2R levels in VAT, while females also presented NPY1R and NPY2R downregulation. Maternal glycation reduces VAT expandability by decreasing NPY2R in overfed animals. Regarding the liver, D1R was decreased in all obesogenic models, while overfeeding induced fat accumulation in both sexes and glycation the inflammatory infiltration. The VAT response to maternal DIO and overfeeding showed a sexual dysmorphism, and exposure to glycotoxins led to a thin-outside-fat-inside phenotype in overfeeding conditions and impaired energy balance, increasing the metabolic risk in adulthood.

Maternal Protein Restriction in Rats Alters Postnatal Growth and Brain Lipid Sensing in Female Offspring.

Perinatal nutrition is a key player in the susceptibility to developing metabolic diseases in adulthood, leading to the concept of "metabolic programming". The aim of this study was to assess the impact of maternal protein restriction during gestation and lactation on glucose homeostasis and eating behaviour in female offspring. Pregnant rats were fed a normal or protein-restricted (PR) diet and followed throughout gestation and lactation. Body weight, glucose homeostasis, and eating behaviour were evaluated in offspring, especially in females. Body weight gain was lower in PR dams during lactation only, despite different food and water intakes throughout gestation and lactation. Plasma concentration of leptin, adiponectin and triglycerides increased drastically before delivery in PR dams in relation to fat deposits. Although all pups had identical birth body weight, PR offspring body weight differed from control offspring around postnatal day 10 and remained lower until adulthood. Offspring glucose homeostasis was mildly impacted by maternal PR, although insulin secretion was reduced for PR rats at adulthood. Food intake, satiety response, and cerebral activation were examined after a lipid preload and demonstrated some differences between the two groups of rats. Maternal PR during gestation and lactation does induce extrauterine growth restriction, accompanied by alterations in maternal plasma leptin and adiponectin levels, which may be involved in programming the alterations in eating behaviour observed in females at adulthood.

The effect of foetal and early childhood growth on metabolic derangements of Sri Lankan children

BackgroundPrevious studies have shown that delayed prenatal growth followed by accelerated postnatal growth plays a significant role on the onset of adult metabolic diseases. The present study aimed to identify the effects of intrauterine and later growth on metabolic derangements among children in Colombo, Sri Lanka.MethodsA school-based cross-sectional study was conducted among 5–15-year-old children selected using a two-stage probability-proportionate-to-size cluster sampling technique. Birth-weight (BW) was extracted from records (denotes prenatal growth) and body mass index(BMI)-Z score and fat mass(FM) measured to denote the current growth of children. Fasting and random blood glucose, lipid profile and blood pressure(BP) were measured. The sample was stratified by age (5—< 10 and 10—15 years); was further categorized into tertiles of BW and BMI-Z scores. Based on these two parameters, metabolic parameters were evaluated within each age category.ResultsThe sample comprised 833(494 boys) healthy school children. Metabolic parameters did not significantly differ by sex or across BW tertiles of each BMI-Z score tertile. However, significant changes in some metabolic parameters were noted across the BMI-Z score tertiles of each BW tertile. Children belonging to the lowest BW and highest BMI-Z score tertiles had worst metabolic profiles, while those in the lowest BW as well as BMI-Z score tertile were protected. Excessive fat deposition seemed to move children to higher BMI-Z score tertiles.ConclusionPoor prenatal growth is not the sole risk factor for abnormal metabolic profile found in childhood. Those who gain fat, denoted by weight, during early childhood are at a higher risk of developing metabolic abnormalities than those who do not. This favours the accelerated postnatal growth hypothesis.

Prenatal smoke (Nicotine) exposure and offspring's metabolic disease susceptibility in adulthood.

Exposure to smoking (nicotine) during pregnancy not only directly affects fetal development, but also increases susceptibility to metabolic diseases in adulthood, but the mechanism of action remains unclear. Here, we review epidemiological and laboratory studies linking these relationships. In addition to the direct effect of nicotine on the fetus, intrauterine neuroendocrine-metabolic programming mediated by maternal glucocorticoid overexposure also plays an important role, involving glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axis, hypothalamic-pituitary-adrenal (HPA) axis, renin-angiotensin system (RAS) and other endocrine systems. Epigenetics is involved in intrauterine neuroendocrine-metabolic programming, metabolic disease susceptibility and multigenerational inheritance. There are "two programming" and "two strikes" mechanisms for the occurrence of fetal-originated metabolic diseases in adulthood. These innovative research summaries and academic viewpoints provide experimental and theoretical basis for systematically elucidating the occurrence and development of fetal-originated metabolic diseases.