Maternal hepatic adaptations during obese pregnancy encompass lobe-specific mitochondrial alterations and oxidative stress.

Maternal obesity (MO) is rising worldwide, affecting half of all gestations, constituting a possible risk-factor for some pregnancy-associated liver diseases (PALD) and hepatic diseases. PALD occur in approximately 3% of pregnancies and are characterized by maternal hepatic oxidative stress (OS) and mitochondrial dysfunction. Maternal hepatic disease increases maternal and fetal morbidity and mortality. Understanding the role of MO on liver function and pathophysiology could be crucial for better understanding the altered pathways leading to PALD and liver disease, possibly paving the way to prevention and adequate management of disease. We investigated specific hepatic metabolic alterations in mitochondria and oxidative stress during MO at late-gestation. Maternal hepatic tissue was collected at 90% gestation in Control and MO ewes (fed 150% of recommended nutrition starting 60 days before conception). Maternal hepatic redox state, mitochondrial respiratory chain (MRC), and OS markers were investigated. MO decreased MRC complex-II activity and its subunits SDHA and SDHB protein expression, increased complex-I and complex-IV activities despite reduced complex-IV subunit mtCO1 protein expression, and increased ATP synthase ATP5A subunit. Hepatic MO-metabolic remodeling was characterized by decreased adenine nucleotide translocator 1 and 2 (ANT-1/2) and voltage-dependent anion channel (VDAC) protein expression and protein kinase A (PKA) activity (P<0.01), and augmented NAD+/NADH ratio due to reduced NADH levels (P<0.01). MO showed an altered redox state with increased OS, increased lipid peroxidation (P<0.01), decreased GSH/GSSG ratio (P=0.005), increased superoxide dismutase (P=0.03) and decreased catalase (P=0.03) antioxidant enzymatic activities, lower catalase, glutathione peroxidase (GPX)-4 and glutathione reductase protein expression (P<0.05), and increased GPX-1 abundance (P=0.03). MO-related hepatic changes were more evident in the right lobe, corroborated by the integrative data analysis. Hepatic tissue from obese pregnant ewes showed alterations in the redox state, consistent with OS and MRC and metabolism remodeling. These are hallmarks of PALD and hepatic disease, supporting MO as a risk-factor and highlighting OS and mitochondrial dysfunction as mechanisms responsible for liver disease predisposition.

Effect of perinatal dietary protein deficiency on some neurochemicals and cytoarchitectural balance, in F1 and F2 generations of rats.

ABSTRACTProtein deficiency, characterized by an inadequate intake of protein in the diet that fails to meet the body's physiological requirements across various stages, can lead to detrimental outcomes. This is of interest due to the persistent low protein content in staple foods and suboptimal dietary patterns. The study sought to assess the intergenerational repercussions of dietary protein deficiency on specific neurochemicals and the cytoarchitecture of the brain within the F1 and F2 generations of rats. The rats were categorized into four groups based on the protein content percentage in their diets: 21% protein diet (21%PD), 10% protein diet (10%PD), 5% protein diet (5%PD), and control diet. Neurobehavior was assessed, while brain serotonin and dopamine levels were measured using HPLC. BDNF and GDNF expression in the hippocampal and prefrontal (PFC) sections, Immunohistochemical investigations of the morphological impact on the hippocampus and PFC, were also analyzed. The protein-deficient groups displayed anxiety, loss of striatal serotonin and increased dopamine levels, degenerated pyramidal cells in the hippocampus, and a prominent reduction in cellular density in the PFC. BDNF and GDNF levels in the PFC were reduced in the 5%PD group. GFAP astrocyte expression was observed to be increased in the prefrontal cortex (PFC) and hippocampal sections, indicating heightened reactivity. The density of hypertrophied cells across generations further suggests the presence of neuroinflammation. Changes in brain structure, neurotransmitter levels, and neurotrophic factor levels may indicate intergenerational alterations in critical regions, potentially serving as indicators of the brain's adaptive response to address protein deficiency across successive generations.

Nutritional consequences and management of hyperemesis gravidarum: a narrative review.

Hyperemesis gravidarum (HG) is a condition at the extreme end of the pregnancy sickness spectrum, estimated to affect 1-2 % of pregnant women. This narrative review provides an overview of the current literature concerning the nutritional implications and management of HG. HG can persist throughout pregnancy, causing malnutrition, dehydration, electrolyte imbalance and unintended weight loss, requiring hospital admission in most cases. In addition to its negative effect on maternal, physical and psychological wellbeing, HG can negatively impact fetal growth and may have adverse consequences on the health of the offspring. HG care and research have been hampered in the past due to stigma, inconsistent diagnostic criteria, mismanagement and lack of investment. Little is known about the nutritional intake of women with HG and whether poor intake at critical stages of pregnancy is associated with perinatal outcomes. Effective treatment requires a combination of medical interventions, lifestyle changes, dietary changes, supportive care and patient education. There is, however, limited evidence-based research on the effectiveness of dietary approaches. Enteral tube feeding and parenteral nutrition are generally reserved for the most intractable cases, where other treatment modalities have failed. Wernicke encephalopathy is a rare but very serious and avoidable consequence of unmanaged HG. A recent priority-setting exercise involving patients, clinicians and researchers highlighted the importance of nutrition research to all. Future research should focus on these priorities to better understand the nutritional implications of HG. Ultimately improved recognition and management of malnutrition in HG is required to prevent complications and optimise nutritional care.

Physical capability in a rural birth cohort at the age of 52: association with early environmental, nutritional, and developmental factors.

INTRODUCTION: Midlife physical capability (PC) is associated with developmental factors in the populations of economically developed countries. As far as we know, there is no information for rural populations of low- and middle-income countries. The aim of the study was to investigate the influence of pre- and postnatal factors on midlife objective measures of PC in a 1966-67 birth cohort from a Mexican rural community. The hypothesis was that adverse developmental conditions are associated with low midlife PC. METHODS: In 1966-67, a birth cohort of all children from a poor Mexican rural community was assembled. Data on family socioeconomic status (SES), parental health and nutritional status, birth weight, postnatal growth and feeding patterns were registered. In 2018, out of the 336 cohort members, 118 were living in the community, and eighty-two of them underwent a comprehensive clinical evaluation. The evaluation included grip strength, gait velocity and chair-stand PC tests. In multivariable linear models, PC tests were the dependent variables, and prenatal, birth and postnatal factors were the independent variables. Adjustment for confounding was made with adult anthropometric, body composition, clinical and ageing status variables. RESULTS: Independent of adult health status and other ageing indicators, lower PC was associated with family organization and SES, parental nutritional status, birth weight, infant postnatal growth velocity, and weaning time. These results indicate that adverse family and environmental conditions that are prevalent in poor rural communities are associated with low midlife PC.

Prevalence and associated factors of undernutrition among pregnant women visiting ANC clinics in Silte zone, Southern Ethiopia.

BACKGROUND: Maternal undernutrition is highly prevalent in underdeveloped countries. Hence, this study was intended to determine the prevalence and associated factors of undernutrition among pregnant women visiting ANC clinics in Silte Zone. METHOD: Facility-based cross-sectional study was conducted from July to January 2019. Systematic random sampling technique was used to select 422 study participants from 11 randomly selected health facilities. Data was collected by using a structured-interviewer administered questionnaire. Mid upper arm circumference (MUAC) was measured by standard non stretchable MUAC tape. Data was entered into a computer using Epi data 3.1 and edited, cleaned, and analyzed using SPSS version 20. Both bivariate and multiple logistic regression analyses were employed to identify factors associated with maternal undernutrition. RESULT: In this study, the overall prevalence of undernutrition among study subjects was 21.8%. Age greater than 31 years of women (AOR = 0.15; 95% CI: 0.03, 0.93), Birth intervals > 2 years (AOR = 0.18; 95% CI: 0.04, 0.76), good nutritional knowledge (AOR = 0.34; 95% CI: 0.17, 0.67), and having no dietary change as a result of current pregnancy AOR = 6.02; 95% CI: 2.99, 12.14) were significantly associated with undernutrition. CONCLUSIONS: The prevalence of undernutrition among pregnant women was 21.8%. Current estimate is lower than previously reported in the study area but higher than reported in developed country. Age of women, Birth intervals, and Dietary change as a result of current pregnancy and Nutrition knowledge were important risk factors/ predictors of undernutrition (MUAC < 23 cm). Interventions targeting maternal nutrition education and child spacing with giving special emphasis to adolescent pregnant women are recommended.

Regional Overview on Maternal Nutrition and Examples of Health System Programme and Policy Responses: Asia and the Pacific.

BACKGROUND: The double burden of malnutrition in Asia and the Pacific is driving a renewed focus on maternal malnutrition. SUMMARY: Though adverse consequences of maternal malnutrition have been long recognized, there is slow progress in addressing nutritional problems of women/adolescent girls. Coverage and quality of current maternal nutrition interventions, mostly delivered through antenatal care programmes vary across countries, and are often sub-optimum. Further, despite a marked increase in overweight and obesity in women of reproductive age, at present, most programmes are focused on under-nutrition and micronutrient deficiencies. Key Messages: The recent antenatal care recommendations released by World Health Organization provide a benchmark for countries to evaluate their programmes and identify gaps and challenges to improving maternal nutrition. Asian and Pacific countries need to address all forms of maternal malnutrition. For countries that historically focused on maternal under-nutrition, expanding their programmes to incorporate interventions to address overweight and obesity will be challenging. Innovative methods for nutrition counselling, both in terms of content and using novel channels of communication, are needed. Protocols and guidance on managing excessive weight gain as well as determining appropriate pregnancy weight gains are needed, while managing micronutrient deficiencies, particularly in settings where inherited disorders of red blood cells exist.

Offspring neuroimmune consequences of maternal malnutrition: Potential mechanism for behavioral impairments that underlie metabolic and neurodevelopmental disorders.

Maternal malnutrition significantly increases offspring risk for both metabolic and neurodevelopmental disorders. Animal models of maternal malnutrition have identified behavioral changes in the adult offspring related to executive function and reward processing. Together, these changes in executive and reward-based behaviors likely contribute to the etiology of both metabolic and neurodevelopmental disorders associated with maternal malnutrition. Concomitant with the behavioral effects, maternal malnutrition alters offspring expression of reward-related molecules and inflammatory signals in brain pathways that control executive function and reward. Neuroimmune pathways and microglial interactions in these specific brain circuits, either in early development or later in adulthood, could directly contribute to the maternal malnutrition-induced behavioral phenotypes. Understanding these mechanisms will help advance treatment strategies for metabolic and neurodevelopmental disorders, especially noninvasive dietary supplementation interventions.

The role of maternal nutrition, metabolic function and the placenta in developmental programming of renal dysfunction.

The intrauterine environment is critical for the development of the foetus. Barker and colleagues were the first to identify that adverse perturbations during foetal development are associated with an increased risk of developing diseases in adulthood, including cardiorenal disease. Specifically for the kidney, perturbations in utero can lead to nephron deficits and renal dysfunction by a number of mechanisms. Altered programming of nephron number is associated with an increased risk of developing kidney disease via glomerular hypertrophy and reduced vasodilative capacity of the renal blood vessels; both of which would contribute to hypertension in adulthood, with males being more susceptible to disease outcomes. Additionally, alterations in the renin-angiotensin system (RAS) such as an upregulation or downregulation of specific receptors, depending on the nature of the insult, have also been implicated in the development of renal dysfunction. Sex-specific differences in the expression of the RAS during late gestation and in the early postnatal environment have also been identified. Extensive research has demonstrated that both uteroplacental insufficiency and maternal malnutrition alter renal development in utero. Equally, exposure to maternal diabetes and maternal obesity during development are also associated with an increased risk of developing renal disease, however, the mechanism behind this association is poorly understood. Therefore, identifying the link between an adverse intrauterine environment and the programmed kidney disease risk in adulthood may facilitate the development of strategies to alleviate the epidemics of cardiorenal disease worldwide, in addition to understanding why males are more susceptible to adult-onset cardiovascular diseases.

Deregulation of ABCG1 early in life contributes to prostate carcinogenesis in maternally malnourished offspring rats.

AIMS: The developmental Origins of Health and Disease (DOHaD) concept has provided the framework to assess how early life experiences can shape health and disease throughout the life course. Using a model of maternal exposure to a low protein diet (LPD; 6% protein) during the gestational and lactational periods, we demonstrated changes in the ventral prostate (VP) transcriptomic landscape in young rats exposed to maternal malnutrition. Male offspring Sprague Dawley rats were submitted to maternal malnutrition during gestation and lactation, and they were weighed, and distance anogenital was measured, followed were euthanized by an overdose of anesthesia at 21 postnatal days. Next, the blood and the ventral prostate (VP) were collected and processed by morphological analysis, biochemical and molecular analyses. RNA-seq analysis identified 411 differentially expressed genes (DEGs) in the VP of maternally malnourished offspring compared to the control group. The molecular pathways enriched by these DEGs are related to cellular development, differentiation, and tissue morphogenesis, all of them involved in both normal prostate development and carcinogenesis. Abcg1 was commonly deregulated in young and old maternally malnourished offspring rats, as well in rodent models of prostate cancer (PCa) and in PCa patients. Our results described ABCG1 as a potential DOHaD gene associated with perturbation of prostate developmental biology with long-lasting effects on carcinogenesis in old offspring rats. A better understanding of these mechanisms may help with the discussion of preventive strategies against early life origins of non-communicable chronic diseases.

Impact of maternal protein restriction on the proteomic landscape of male rat lungs across the lifespan.

The developmental origins of healthy and disease (DOHaD) concept has demonstrated a higher rate of chronic diseases in the adult population of individuals whose mothers experienced severe maternal protein restriction (MPR). Using proteomic and in silico analyses, we investigated the lung proteomic profile of young and aged rats exposed to MPR during pregnancy and lactation. Our results demonstrated that MPR lead to structural and immune system pathways changes, and this outcome is coupled with a rise in the PI3k-AKT-mTOR signaling pathway, with increased MMP-2 activity, and CD8 expression in the early life, with long-term effects with aging. This led to the identification of commonly or inversely differentially expressed targets in early life and aging, revealing dysregulated pathways related to the immune system, stress, muscle contraction, tight junctions, and hemostasis. We identified three miRNAs (miR-378a-3p, miR-378a-5p, let-7a-5p) that regulate four proteins (ACTN4, PPIA, HSPA5, CALM1) as probable epigenetic lung marks generated by MPR. In conclusion, MPR impacts the lungs early in life, increasing the possibility of long-lasting negative outcomes for respiratory disorders in the offspring.

Abnormal epigenetic memory of mesenchymal stem and progenitor cells caused by fetal malnutrition induces hypertension and renal injury in adulthood.

Fetal malnutrition has been reported to induce hypertension and renal injury in adulthood. We hypothesized that this hypertension and renal injury would be associated with abnormal epigenetic memory of stem and progenitor cells contributing to organization in offspring due to fetal malnutrition. We measured blood pressure (BP) for 60 weeks in offspring of pregnant rats fed a normal protein diet (Control), low-protein diet (LP), and LP plus taurine (LPT) in the fetal period. We used western blot analysis to evaluate the expression of αSMA and renin in CD44-positive renal mesenchymal stem cells (MSCs) during differentiation by TGF-ß1. We measured kidney label-retaining cells (LRCs) at 11 weeks of age and formation of endothelial progenitor cells (EPCs) at 60 weeks of age from the offspring with fetal malnutrition. Epigenetics of the renal MSCs at 14 weeks were investigated by ATAC-sequence and RNA-sequence analyses. BP was significantly higher in LP than that in Control and LPT after 45-60 weeks of age. Numbers of LRCs and EPC colonies were significantly lower in LP than in Control. Renal MSCs from LP already showed expression of h-caldesmon, αSMA, LXRα, and renin before their differentiation. Epigenetic analyses identified PAR2, Chac1, and Tspan6 genes in the abnormal differentiation of renal MSCs. These findings suggested that epigenetic abnormalities of stem and progenitor cell memory cause hypertension and renal injury that appear in adulthood of offspring with fetal malnutrition.

Maternal malnutrition associated with postnatal sugar consumption increases inflammatory response and prostate disorders in rat offspring.

Maternal malnutrition can alter developmental biology, programming health and disease in offspring. The increase in sugar consumption during the peripubertal period, a worldwide concern, also affects health through adulthood. Studies have shown that maternal exposure to a low protein diet (LPD) is associated with an increase in prostate disease with aging. However, the combined effects of maternal LPD and early postnatal sugar consumption on offspring prostate disorders were not investigated. The effects on aging were evaluated using a maternal gestational model with lactational LPD (6% protein) and sugar consumption (10%) from postnatal day (PND) 21-90, associating the consequences on ventral prostate (VP) rats morphophysiology on PND540. An increase was shown in mast cells and in the VP of the CTR + SUG and Gestational and Lactational Low Protein (GLLP) groups. In GLLP + SUG, a significant increase was shown in TGF-ß1 expression in both the systemic and intra-prostatic forms, and SMAD2/3p had increased. The study identified maternal LPD and sugar consumption as risk factors for prostatic homeostasis in senility, activating the TGFß1-SMAD2/3 pathway, a signaling pathway with potential markers for prostatic disorders.

Global disability-adjusted life years and deaths attributable to child and maternal malnutrition from 1990 to 2019.

Background: Child and maternal malnutrition (CMM) caused heavy disability-adjusted life years (DALY) and deaths globally. It is crucial to understand the global burden associated with CMM in order to prioritize prevention and control efforts. We performed a comprehensive analysis of the global DALY and deaths attributable to CMM from 1990 to 2019 in this study. Methods: The age-standardized CMM related burden including DALY and death from 1990 to 2019 were accessed from the Global Burden of Disease study 2019 (GBD 2019). The changing trend were described by average annual percentage change (AAPC). The relationship between sociodemographic factors and burden attributable to CMM were explored by generalized linear model (GLM). Results: Globally, in 2019, the age-standardized DALY and death rates of CMM were 4,425.24/100,000 (95% UI: 3,789.81/100,000-5,249.55/100,000) and 44.72/100,000 (95% UI: 37.83/100,000-53.47/100,000), respectively. The age-standardized DALY rate (AAPC = -2.92, 95% CI: -2.97% to -2.87%) and death rates (AAPC = -3.19, 95% CI: -3.27% to -3.12%) presented significantly declining trends during past 30 years. However, CMM still caused heavy burden in age group of <28 days, Sub-Saharan Africa and low SDI regions. And, low birth weight and short gestation has identified as the primary risk factors globally. The GLM indicated that the highly per capita gross domestic product, per capita current health expenditure, physicians per 1,000 people were contributed to reduce the burden attributable to CMM. Conclusion: Although global burden attributable to CMM has significantly declined, it still caused severe health burden annually. To strengthen interventions and address resources allocation in the vulnerable population and regions is necessary.

Maternal high-fat or low-protein diets promote autism-related behavior and altered social behavior within groups in offspring male mice.

Maternal malnutrition has been associated with neurodevelopmental deficits and long-term implications on the offspring's health and behavior. Here, we investigated the effects of maternal low-protein diet (LPD) or obesity-inducing maternal high-fat diet (HFD) on dyadic social interactions, group organization and autism-related behaviors in mice. We found that maternal HFD induced an autism-related behavioral phenotype in the male offspring, including a robust decrease in sociability, increased aggression, cognitive rigidity and repetitive behaviors. Maternal LPD led to a milder yet significant effect on autism-related symptoms, with no effects on olfactory-mediated social behavior. Under naturalistic conditions in a group setting, this manifested in altered behavioral repertoires, increased magnitude in dominance relations, and reduced interactions with novel social stimuli in the HFD male offspring, but not in the LPD offspring. Finally, we found HFD-induced transcriptomic changes in the olfactory bulbs of the male offspring. Together, our findings show that maternal malnutrition induces long-lasting effects on aggression and autism-related behaviors in male offspring, and potential impairments in brain regions processing chemosensory signals.

Establishing human microbial observatory programs in low- and middle-income countries.

Studies of the human microbiome are progressing rapidly but have largely focused on populations living in high-income countries. With increasing evidence that the microbiome contributes to the pathogenesis of diseases that affect infants, children, and adults in low- and middle-income countries (LMICs), and with profound and rapid ongoing changes occurring in our lifestyles and biosphere, understanding the origins of and developing microbiome-directed therapeutics for treating a number of global health challenges requires the development of programs for studying human microbial ecology in LMICs. Here, we discuss how the establishment of long-term human microbial observatory programs in selected LMICs could provide one timely approach.

Recent Advances in Hypertension: Epigenetic Mechanism Involved in Development of Salt-Sensitive Hypertension.

This review highlights recent insights into the epigenetic mechanism of salt-sensitive hypertension from the fetus to the elderly population, mainly focusing on the DNA methylation and histone modification-mediated regulation of hypertension-associated genes. Maternal malnutrition during pregnancy induces upregulation of AT1a (angiotensin receptor 1a) by aberrant DNA methylation, and increased AT1A activity in the hypothalamus develops prenatally programmed salt-sensitive hypertension through renal sympathetic overactivity. In addition, maternal lipopolysaccharide exposure during pregnancy induces upregulation of the Rac1 gene through histone modification by H3K9me2 across generations, resulting in salt-induced activation of the Rac1-MR (mineralocorticoid receptor) pathway in the kidney and the development of salt-sensitive hypertension in F4 and F5 offspring. In mice, aberrant DNA methylation of the Klotho gene, which regulates aging-associated hypertension, decreases the circulating soluble Klotho levels, leading to activation of the vascular Wnt5a-RhoA pathway and vasoconstriction and development of salt-sensitive hypertension because of decreased renal blood flow. A detailed understanding of the environmentally-induced epigenetic modulations related to salt-induced hypertension could be promising for developing preventive and therapeutic approaches to hypertension.

Low glomerular number at birth can lead to the development of chronic kidney disease.

Chronic kidney disease (CKD) prevalence is increasing worldwide, and reducing the number of patients with CKD is of utmost importance. The environment during the fetal, perinatal, and early childhood stages may influence CKD development (developmental origins of health and disease). Under conditions of maternal malnutrition, the glomerular number of infants reduces, and the risk of developing CKD may increase. Nephron progenitor cells and ureteric buds interact with each other to form glomeruli at the tip of the ureteric bud. Thus, the number of glomeruli is determined by the number of ureteric bud branches, which are reportedly decreased due to maternal malnutrition, in turn reducing the glomerular number. Four possible mechanisms can explain the low glomerular number resulting from maternal malnutrition: 1) suppression of c-Ret expression, 2) suppression of nephron formation by renin-angiotensin-aldosterone system inhibition, 3) exposure to excess glucocorticoids, and 4) promotion of apoptosis. Additionally, nephron formation does not continue after birth in humans. Therefore, a low glomerular number at birth is a lifelong burden on the glomeruli and increases the risk of developing CKD. Therefore, it is important to maintain the glomerular number at birth. Accurate glomerular counts are essential for conducting studies on the glomerular number. The dissector/fractionator method is the gold standard; however, it can only be performed at some institutions. Recently, methods have been developed to measure the glomerular number by combining computed tomography and pathological examination and measure the glomerular count using magnetic resonance imaging. Models of decreased and increased glomerular numbers have been developed. Moreover, research regarding the causes of decreased glomerular number and its relationship with development of lifestyle-related diseases and renal dysfunction has significantly progressed, furthering our understanding of the importance of glomerular number.

Evidence-based interventions to reduce maternal malnutrition in low and middle-income countries: a systematic review.

Introduction: Despite remarkable strides in global efforts to reduce maternal mortality, low-and middle-income countries (LMICs) continue to grapple with a disproportionate burden of maternal mortality, with malnutrition emerging as a significant contributing factor to this enduring challenge. Shockingly, malnourished women face a mortality risk that is twice as high as their well-nourished counterparts, and a staggering 95% of maternal deaths in 2020 occurred within LMICs. The critical importance of addressing maternal malnutrition in resource-constrained settings cannot be overstated, as compelling research studies have demonstrated that such efforts could potentially save thousands of lives. However, the landscape is marred by a scarcity of evidence-based interventions (EBIs) specifically tailored for pregnant individuals aimed at combatting maternal malnutrition and reducing mortality rates. It is against this backdrop that our study endeavors to dissect the feasibility, adoption, sustainability, and cost-effectiveness of EBIs designed to combat maternal malnutrition. Methods: Our comprehensive search encompassed eight prominent databases covering the period from 2003 to 2022 in LMICs. We began our study with a comprehensive search across multiple databases, yielding a total of 149 studies. From this initial pool, we eliminated duplicate entries and the remaining studies underwent a thorough screening process resulting in the identification of 63 full-text articles that aligned with our predefined inclusion criteria. Results: The meticulous full-text review left us with a core selection of six articles that shed light on interventions primarily centered around supplementation. They underscored a critical issue -the limited understanding of effective implementation in these countries, primarily attributed to inadequate monitoring and evaluation of interventions and insufficient training of healthcare professionals. Moreover, our findings emphasize the pivotal role of contextual factors, such as cultural nuances, public trust in healthcare, the prevalence of misinformation, and concerns regarding potential adverse effects of interventions, which profoundly influence the successful implementation of these programs. Discussion: While the EBIs have shown promise in reducing maternal malnutrition, their true potential for feasibility, adoption, cost-effectiveness, and sustainability hinges on their integration into comprehensive programs addressing broader issues like food insecurity and the prevention of both communicable and non-communicable diseases.

Protein restriction during lactation causes transgenerational metabolic dysfunction in adult rat offspring.

Introduction: Protein restriction during lactation can induce metabolic dysfunctions and has a huge impact on the offspring's phenotype later in its life. We tested whether the effects of a maternal low-protein diet (LP) in rats can be transmitted to the F2 generation and increase their vulnerability to dietary insults in adulthood. Methods: Female Wistar rats (F0) were fed either a low-protein diet (LP; 4% protein) during the first 2 weeks of lactation or a normal-protein diet (NP; 23% protein). The female offspring (F1 generation) were maintained on a standard diet throughout the experiment. Once adulthood was reached, female F1 offspring from both groups (i.e., NP-F1 and LP-F1) were bred to proven males, outside the experiment, to produce the F2 generation. Male F2 offspring from both groups (NP-F2 and LP-F2 groups) received a standard diet until 60 days old, at which point they received either a normal fat (NF; 4.5% fat) or a high fat diet (HF; 35% fat) for 30 days. Results: At 90 days old, LPNF-F2 offspring had increased lipogenesis and fasting insulinemia compared to NPNF-F2, without alteration in insulin sensitivity. HF diet caused increased gluconeogenesis and displayed glucose intolerance in LPHF-F2 offspring compared to LPNF-F2 offspring. Additionally, the HF diet led to damage to lipid metabolism (such as steatosis grade 3), higher body weight, fat pad stores, and hepatic lipid content. Discussion: We concluded that an F0 maternal protein restricted diet during lactation can induce a transgenerational effect on glucose and liver metabolism in the F2 generation, making the offspring's liver more vulnerable to nutritional injury later in life.