Search Results (169)

Childhood obesity is a growing global health concern, with established links to physical activity, nutrition, and, increasingly, to prenatal and perinatal factors. Emerging evidence highlights the significant role of maternal conditions such as obesity, comorbidities, nutrition, and environmental exposures in predisposing offspring to long-term metabolic and cardiovascular diseases. The “Developmental Origins of Health and Disease” (DOHaD) paradigm provides a framework for understanding how early life environmental exposures, particularly during the periconceptional, fetal, and neonatal periods, can program future health outcomes through epigenetic mechanisms. Epigenetic modifications alter gene expression without changing the DNA sequence and are increasingly recognized as key mediators in the development of obesity. This narrative review summarizes current findings on the early determinants of childhood obesity, emphasizing the molecular and epigenetic pathways involved. A comprehensive literature search was conducted across multiple databases and international sources, focusing on recent studies from the past decade. Both human and animal research were included to provide a broad perspective. This review aims to consolidate recent insights into early life influences on obesity, underscoring the need for preventive strategies starting as early as the preconception period. Full article

Cardiovascular–kidney–metabolic (CKM) syndrome underscores the interconnected biology of cardiovascular disease, kidney disease, and metabolic disorders such as obesity and type 2 diabetes. Although now recognized as a growing global health burden, accumulating preclinical evidence suggests that CKM syndrome may originate in early life—a concept rooted in the developmental origins of health and disease (DOHaD) framework. Animal studies have greatly enhanced our comprehension of these mechanisms, emphasizing the promise of early interventions that focus on antioxidants and gut microbiota modulation to mitigate the development of CKM conditions. Resveratrol, a natural antioxidant and prebiotic, alongside short-chain fatty acids (SCFAs), a postbiotic, have demonstrated the ability to modulate gut microbiota and oxidative stress in experimental models. Various resveratrol derivatives have also been engineered to improve bioavailability, though their effects remain largely confined to animal studies. This review synthesizes preclinical findings on the impact of perinatal oxidative stress and gut dysbiosis on CKM outcomes, critically examining the roles of resveratrol, SCFAs, and their derivatives in animal models. Finally, we highlight the significant translational gap between experimental research and clinical application, underscoring the need for human studies to validate these early-life intervention strategies. Full article

Background/Objectives: Intrauterine growth restriction (IUGR) is associated with enhanced inflammatory activity, poor skeletal muscle glucose metabolism, and pancreatic β cell dysfunction that persist in offspring. We hypothesized that targeting heightened inflammation in IUGR-born neonatal lambs by supplementing anti-inflammatory ω-3 polyunsaturated fatty acids (ω-3 PUFAs) would improve metabolic outcomes. Methods: Maternal heat stress was used to produce IUGR lambs, which received daily oral boluses of ω-3 PUFA Ca²⁺ salts or placebo for 30 days. Results: Greater circulating TNFα and semitendinosus IL6R in IUGR lambs were fully resolved by ω-3 PUFA, and impaired glucose-stimulated insulin secretion, muscle glucose oxidation, and hypertension were partially rescued. Impaired glucose oxidation by IUGR muscle coincided with a greater glycogen content that was completely reversed by ω-3 PUFA and greater lactate production that was partially reversed. Ex vivo O₂ consumption was increased in IUGR muscle, indicating compensatory lipid oxidation. This too was alleviated by ω-3 PUFA. Conversely, ω-3 PUFA had little effect on IUGR-induced changes in lipid flux and hematology parameters, did not resolve greater muscle TNFR1, and further reduced muscle β2-adrenoceptor content. Conclusions: These findings show that targeting elevated inflammatory activity in IUGR-born lambs in the early neonatal period improved metabolic outcomes, particularly muscle glucose metabolism and β cell function. Full article

Pediatric chronic kidney disease (CKD) is a growing concern that often originates early in life, yet significant challenges remain in translating clinical guidelines into real-world practice. World Kidney Day 2025 highlights the importance of early detection, but the three levels of preventive strategies commonly recommended for adults may not be directly applicable to children. Unlike adult CKD, primary prevention in pediatrics should focus on prenatal, neonatal, and early-life factors such as congenital anomalies of the kidney and urinary tract (CAKUT), preterm birth, maternal health, and environmental exposures. Secondary prevention, involving early detection through screening, is crucial, yet the effectiveness of mass urinary screening in children remains a subject of global debate. Several key challenges persist, including the accurate estimation of glomerular filtration rate (eGFR), consistent definition and diagnosis of pediatric hypertension, identification of reliable biomarkers, and targeted screening in specific pediatric populations. Although clear guidelines exist to manage CKD progression and enhance quality of life, a critical gap remains between what is known and what is practiced. Closing this gap requires robust evidence to inform best practices, improve health-related quality of life, and advance pediatric kidney replacement therapies. To protect and improve kidney health for every child worldwide, these challenges must be acknowledged, and sustainable, evidence-based solutions must be developed and implemented without further delay. Full article

Kidney disease and hypertension are interconnected, prevalent conditions that affect both pregnant women and children. Oxidative stress occurs when reactive oxygen species or reactive nitrogen species exceed the capacity of antioxidant systems. It plays a critical role in kidney development, resulting in kidney programming and increased risks for kidney disease and hypertension across the life course. Animal models have significantly advanced our understanding of oxidative stress-related kidney programming, the molecular mechanisms involved, and early-life antioxidant interventions to prevent kidney disease. This review critically examines the influence of perinatal oxidative stress on kidney development, highlighting its long-term effects on kidney outcomes and susceptibility to hypertension. It also explores the potential of antioxidant-based interventions in preventing kidney disease and hypertension. Furthermore, the review addresses the existing gap between insights gained from animal models and their translation into clinical practices, emphasizing the challenges and opportunities for future research in this area. Full article

The global incidence and prevalence of cardiometabolic disorders have risen significantly in recent years. Although lifestyle choices in adulthood play a crucial role in the development of these conditions, it is well established that events occurring early in life can have an important effect. Recent research on cardiometabolic diseases has highlighted the influence of sexual dimorphism on risk factors, underlying mechanisms, and response to therapies. In this narrative review, we summarize the current understanding of sexual dimorphism in cardiovascular and metabolic diseases in the general population and within the framework of the Developmental Origins of Health and Disease (DOHaD) concept. We explore key risk factors and mechanisms, including the influence of genetic and epigenetic factors, placental and embryonic development, maternal nutrition, sex hormones, energy metabolism, microbiota, oxidative stress, cell death, inflammation, endothelial dysfunction, circadian rhythm, and lifestyle factors. Finally, we discuss some of the main therapeutic approaches, responses to which may be influenced by sexual dimorphism, such as antihypertensive and cardiovascular treatments, oxidative stress management, nutrition, cell therapies, and hormone replacement therapy. Full article

The benefits of breastfeeding for both mother and infant are generally recognized; however, the connections between breast milk, lactation, and long-term offspring health and disease remain incompletely understood. Cardiovascular–kidney–metabolic syndrome (CKMS) has become a major global public health challenge. Insufficient breast milk supply, combined with various early-life environmental factors, markedly increases the future risk of CKMS, as highlighted by the developmental origins of health and disease (DOHaD) concept. Given its richness in nutrients and bioactive components essential for infant health, this review focuses on reprogramming strategies involving breast milk to improve offspring’s cardiovascular, kidney, and metabolic health. It also highlights recent experimental advances in understanding the mechanisms driving CKMS programming. Cumulatively, the evidence suggests that lactational impairment heightens the risk of CKMS development. In contrast, early interventions during the lactation period focused on animal models that leverage breast milk components in response to early-life cues show potential in improving cardiovascular, kidney, and metabolic outcomes—an area warranting further investigation and clinical translation. Full article

Background: Gestational diabetes mellitus (GDM), characterized by gestational hyperglycemia due to insufficient insulin response, poses significant risks to both maternal and offspring health. Fetal exposure to maternal hyperglycemia leads to short-term complications such as macrosomia and neonatal hypoglycemia and long-term risks including obesity, metabolic syndrome, cardiovascular dysfunction, and type 2 diabetes. The Developmental Origins of Health and Disease (DOHaD) theory explains how maternal hyperglycemia alters fetal programming, increasing susceptibility to metabolic disorders later in life. Objective: This review explores the intergenerational impact of GDM, linking maternal hyperglycemia to lifelong metabolic, cardiovascular, and neurodevelopmental risks via epigenetic and microbiome alterations. It integrates the most recent findings, contrasts diagnostic methods, and offers clinical strategies for early intervention and prevention. Methods: A comprehensive literature search was conducted in PubMed, Scopus, and ScienceDirect to identify relevant studies published between 1 January 2000 and 31 December 2024. The search included studies focusing on the metabolic and developmental consequences of GDM exposure in offspring, as well as potential mechanisms such as epigenetic alterations and gut microbiota dysbiosis. Studies examining preventive strategies and management approaches were also included. Key Findings: Maternal hyperglycemia leads to long-term metabolic changes in offspring, with epigenetic modifications and gut microbiota alterations playing key roles. GDM-exposed children face increased risks of obesity, glucose intolerance, and cardiovascular diseases. Early screening and monitoring are crucial for risk reduction. Practical Implications: Understanding the intergenerational effects of GDM has important clinical implications for prenatal and postnatal care. Early detection, lifestyle interventions, and targeted postnatal surveillance are essential for reducing long-term health risks in offspring. These findings emphasize the importance of comprehensive maternal healthcare strategies to improve long-term outcomes for both mothers and their children. Full article

We are exposed to a variety of environmental chemicals in our daily lives. It is possible that the effects of this daily chemical exposure could accumulate in the organism in some form and influence health and disease development. The exposure effects extend throughout the human lifetime, not only after birth, but also during the embryonic period. Epigenetics is an important target for the molecular mechanisms of daily environmental chemical effects. Epigenetics is a mechanism of gene transcription regulation that does not involve changes in DNA sequence. The Developmental Origins of Health and Disease (DOHaD) theory has also been proposed, in which effects such as exposure to environmental chemicals during embryonic period are mediated by epigenetic changes, which may lead to risk for disease development and adverse health effects after maturity. This review summarizes the association between embryonic exposure and the epigenetics of well-known non-essential toxic heavy metals (methylmercury, cadmium, arsenic, and lead), a representative group of environmental chemicals. In the future, it will be important to predict the epigenetic mechanisms of unknown chemical and combined exposures. In addition, further experimental investigations using experimental animals and the accumulation of knowledge are needed to study the transgenerational effects of environmental chemicals in the future. Full article

Cardiovascular–kidney–metabolic syndrome (CKMS) has become a significant global health challenge. Since CKMS often originates early in life, as outlined by the developmental origins of health and disease (DOHaD) concept, prevention is a more effective strategy than treatment. Various animal models, classified by environmental exposures or mechanisms, are used to explore the developmental origins of CKMS. However, no single model can fully replicate all aspects of CKMS or its clinical stages, limiting the advancement of preventive and therapeutic strategies. This review aims to assist researchers by comparing the strengths and limitations of common animal models used in CKMS programming studies and highlighting key considerations for selecting suitable models. Full article

While advancements in early detection and improved access to care have significantly enhanced breast cancer survival rates, the disease remains a significant global malignancy, constituting approximately 12.5% of all new cancer cases and claiming nearly 700,000 lives in 2020. As a result, there is widespread consensus that the most sustainable solution lies in prevention. Indeed, preventive strategies, including lifestyle modifications and research into risk-reducing interventions, offer the potential to address the root causes of noncommunicable diseases such as breast cancer. While conventional wisdom has long attributed established risk factors for breast cancer to age, lifestyle, familial history, and reproductive factors, evidence highlights the maternal environment as a pivotal stage for fetal programming of disease risk, as elucidated in the developmental origins of health and disease (DOHaD) framework. Consequently, a growing body of research has been focused on elucidating epigenomic signatures that influence fetal development while shaping health outcomes and susceptibility to diseases later in life. This review aims to identify fetal mammary developmental genes that have been implicated in breast cancer etiology and the potential interplay of maternal environment in epigenetic programming of breast cancer risk in adulthood. Full article

Intrauterine growth restriction (IUGR) is a risk factor for postnatal cardiovascular, metabolic, and psychiatric disorders. In most IUGR models, placental dysfunction that causes reduced 11β-hydroxysteroid dehydrogenase 2 (11βHSD2) activity, which degrades glucocorticoids (GCs) in the placenta, resulting in fetal GC overexposure. This overexposure to GCs continues to affect not only intrauterine fetal development itself, but also the metabolic status and neural activity in adulthood through epigenetic changes such as microRNA change, histone modification, and DNA methylation. We have shown that the IUGR model induced DNA hypomethylation in the paraventricular nucleus (PVN) in the brain, which in turn activates sympathetic activities, the renin–angiotensin system (RAS), contributing to the development of salt-sensitive hypertension. Even in adulthood, strong stress and/or exogenous steroids have been shown to induce epigenetic changes in the brain. Furthermore, DNA hypomethylation in the PVN is also observed in other hypertensive rat models, which suggests that it contributes significantly to the origins of elevated blood pressure. These findings suggest that if we can alter epigenetic changes in the brain, we can treat or prevent hypertension. Full article

The complex relationship between kidney disease and hypertension represents a critical area of research, yet less attention has been devoted to exploring how this connection develops early in life. Various environmental factors during pregnancy and lactation can significantly impact kidney development, potentially leading to kidney programming that results in alterations in both structure and function. This early programming can contribute to adverse long-term kidney outcomes, such as hypertension. In the context of kidney programming, the molecular pathways involved in hypertension are intricate and include epigenetic modifications, oxidative stress, impaired nitric oxide pathway, inappropriate renin–angiotensin system (RAS) activation, disrupted nutrient sensing, gut microbiota dysbiosis, and altered sodium transport. This review examines each of these mechanisms and highlights reprogramming interventions proposed in preclinical studies to prevent hypertension related to kidney programming. Given that reprogramming strategies differ considerably from conventional treatments for hypertension in kidney disease, it is essential to shift focus toward understanding the processes of kidney programming and its role in the development of programmed hypertension. Full article

The Developmental Origins of Health and Disease (DOHaD) framework has highlighted the role of maternal and paternal health on disease risk in offspring and across generations. Although adolescence is increasingly recognised as a key DOHaD window where interventions may have the greatest impact in breaking the cycle of non-communicable diseases, data around the recognition of this concept in adolescents remain limited. Previous work by our group found that the understanding of DOHaD-related concepts among adolescents in New Zealand was low, including some adolescents showing disagreement with key DOHaD concepts. This qualitative study aimed to explore DOHaD perspectives and understandings among a group of adolescents who responded to the survey using semi-structured focus groups and interviews (n = 12). Four core themes were identified: 1. knowledge of DOHaD and DOHaD-related terminology; 2. understanding different life course windows for DOHaD interventions; 3. recognising that DOHaD-related information needs to be accessible for adolescents; and 4. the importance of developing context-specific resources for adolescents. Adolescents in this study indicated that they had not heard of DOHaD or related terminology. Although the majority recognised that there were many important life stages for potential interventions, there was a strong emphasis on adolescence as a key window of opportunity. Adolescents suggested that more could be done in schools to help promote awareness and understanding of DOHaD-related concepts during the later years of schooling. The development of future resources needs to be contextually specific for adolescents to ensure increased uptake of information during this important developmental window. Full article

Maternal nutrition during the critical period of pregnancy increases the susceptibility of offspring to the development of diseases later in life. This study aimed to analyze metabolite profiles to investigate the effect of maternal diet during pregnancy on changes in offspring plasma metabolites and to identify correlations with metabolic parameters. Pregnant Sprague-Dawley rats were exposed to under- and overnutrition compared to controls, and their offspring were fed a standard diet after birth. Plasma metabolism was profiled in offspring at 16 weeks of age using liquid chromatography–mass spectrometry (LC-MS/MS) and gas chromatography–tandem mass spectrometry (GC-MS/MS). We analyzed 80 metabolites to identify distinct metabolites and metabolic and neurodegenerative disease-associated metabolites that were sex-differentially altered in each group compared to controls (p < 0.05, VIP score > 1.0). Specifically, changes in 3-indolepropionic acid, anthranilic acid, linoleic acid, and arachidonic acid, which are involved in tryptophan and linoleic acid metabolism, were observed in male offspring and correlated with plasma leptin levels in male offspring. Our results suggest that fatty acids involved in tryptophan and linoleic acid metabolism, which are altered by the maternal diet during pregnancy, may lead to an increased risk of metabolic and neurodegenerative diseases in the early life of male offspring. Full article