Nutritional manipulations in the perinatal period program adipose tissue in offspring

2013 ◽  
Vol 305 (10) ◽  
pp. E1195-E1207 ◽  
Author(s):  
Marie-Amélie Lukaszewski ◽  
Delphine Eberlé ◽  
Didier Vieau ◽  
Christophe Breton

Epidemiological studies demonstrated initially that maternal undernutrition results in low birth weight with increased risk for long-lasting energy balance disorders. Maternal obesity and diabetes associated with high birth weight, excessive nutrition in neonates, and rapid catchup growth also increase the risk of adult-onset obesity. As stated by the Developmental Origin of Health and Disease concept, nutrient supply perturbations in the fetus or neonate result in long-term programming of individual body weight set point. Adipose tissue is a key fuel storage unit involved mainly in the maintenance of energy homeostasis. Studies in numerous animal models have demonstrated that the adipose tissue is the focus of developmental programming events in a sex- and depot-specific manner. In rodents, adipose tissue development is particularly active during the perinatal period, especially during the last week of gestation and during early postnatal life. In contrast to rodents, this process essentially takes place before birth in bigger mammals. Despite these different developmental time windows, altricial and precocial species share several mechanisms of adipose tissue programming. Offspring from malnourished dams present adipose tissue with a series of alterations: impaired glucose uptake, insulin and leptin resistance, low-grade inflammation, modified sympathetic activity with reduced noradrenergic innervations, and thermogenesis. These modifications reprogram adipose tissue metabolism by changing fat distribution and composition and by enhancing adipogenesis, predisposing the offspring to fat accumulation. Subtle adipose tissue circadian rhythm changes are also observed. Inappropriate hormone levels, modified tissue sensitivity (especially glucocorticoid system), and epigenetic mechanisms are key factors for adipose tissue programming during the perinatal period.

Author(s):  
Christophe Breton

AbstractThe epidemiological studies initially indicated that maternal undernutrition leading to a low birth weight may predispose to the long-lasting energy balance disorders. A high birth weight due to maternal obesity or diabetes, inappropriate early postnatal nutrition, and rapid catch-up growth, may also sensitize to an increased risk of obesity. As stated by the developmental origin of health and disease concept, the perinatal perturbation of the fetus/neonate nutrient supply might be a crucial determinant of the individual programming of the body weight set point. The adipose tissue is considered as the main fuel storage unit involved in the maintenance of the energy homeostasis. Several models have demonstrated that this tissue is a prime target of the developmental programming in a gender- and depot-specific manner. In the rodents, the perinatal period of life corresponds largely to the period of adipogenesis. In contrast, this phenomenon essentially takes place before birth in bigger mammals. Despite these different developmental time windows, the altricial and precocial species share several common offspring programming mechanisms. Thus, the adipose tissue of the offspring from malnourished dams exhibited impaired glucose uptake and leptin/insulin resistance with increased proinflammatory markers. It also displayed a modified sympathetic activity, circadian rhythm, fatty acid composition, and thermogenesis. This might lead to the reprogrammed metabolism and distribution of the adipose tissue with enhanced adipogenesis and fat accumulation predisposing to adiposity. The inappropriate glucocorticoid (GC) levels and modified tissue sensitivity might be key actors of perinatal programming and long-lasting altered adipose tissue activity in the offspring. Following maternal malnutrition, the epigenetic mechanisms might also be responsible for the adipose tissue programming.


2012 ◽  
Vol 216 (2) ◽  
pp. R19-R31 ◽  
Author(s):  
Christophe Breton

Epidemiological studies initially demonstrated that maternal undernutrition leading to low birth weight may predispose for energy balance disorders throughout life. High birth weight due to maternal obesity or diabetes, inappropriate early post-natal nutrition and rapid catch-up growth may also sensitise to increased risk of obesity. As stated by the Developmental Origin of Health and Disease concept, the perinatal perturbation of foetus/neonate nutrient supply might be a crucial determinant of individual programming of body weight set point. The hypothalamus–adipose axis plays a pivotal role in the maintenance of energy homoeostasis controlling the nutritional status and energy storage level. The perinatal period largely corresponds to the period of brain maturation, neuronal differentiation and active adipogenesis in rodents. Numerous dams and/or foetus/neonate dietary manipulation models were developed to investigate the mechanisms underlying perinatal programming in rodents. These models showed several common offspring hypothalamic consequences such as impaired neurogenesis, neuronal functionality, nuclei structural organisation and feeding circuitry hardwiring. These alterations led to a persistent reprogrammed appetite system that favoured the orexigenic pathways, leptin/insulin resistance and hyperphagia. Impaired hypothalamic sympathetic outflow to adipose tissue and/or reduced innervation may also account for modified fat cell metabolism. Thus, enhanced adipogenesis and/or lipogenesis capacities may predispose the offspring to fat accumulation. Abnormal hypothalamus–adipose axis circadian rhythms were also evidenced. This review mainly focuses on studies in rodents. It highlights hormonal and epigenetic mechanisms responsible for long-lasting programming of energy balance in the offspring. Dietary supplementation may provide a therapeutic option using a specific regimen for reversing adverse programming outcomes in humans.


Author(s):  
Kristin André ◽  
Andrea Stuart ◽  
Kärin Kallén

Objective. To determine risk and protective factors of obstetric anal sphincter injuries (OASIS). Design. A retrospective register-based observational study. Setting. Sweden. Population. A cohort of 988, 988 singleton term deliveries 2005-2016 were included. Methods. Data from the Swedish Medical Birth Registry and Statistics Sweden were extracted to identify cases of OASIS and maternal and foetal characteristics. Modified Poisson Regression analyses were performed to assess risk factors. Main outcome measures. Risk ratios for OASIS with 95% confidence interval associated with maternal and foetal risk factors were calculated. Results. The rate of OASIS was 3.5% (n=34, 583). Primiparity (aRR 3.13 95% CI 3.05–3.21), vacuum extraction (aRR 2.79 95% CI 2.73–2.86), forceps (aRR 4.27 95% CI 3.86–4.72) and high birth weight (aRR 2.61 95% CI 2.50–2.72) were associated with a significantly increased risk of OASIS. Increasing maternal age and decreasing maternal height increased the risk of OASIS. Smoking (aRR 0.74 95% CI 0.70–0.79) and low maternal education (aRR 0.87 95% CI 0.83–0.92) were associated with a decreased frequency of reported OASIS. Obesity decreased the risk of OASIS (aRR 0.90 95% CI 0.87–0.94), but only after adjusting for foetal birth weight. Previous caesarean section increased the risk of OASIS (aRR 1.41; 95% CI 1.36–1.47). Conclusion. Primiparity, instrumental delivery and high birth weight increased the risk of OASIS. Risk factors including BMI, height, age, smoking, maternal education, ethnicity and previous caesarean section also contribute to the overall risk of OASIS. Keywords. Obstetric sphincter injuries, risk factors, pregnancy.


BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e024532 ◽  
Author(s):  
Zhiyong Zou ◽  
Zhongping Yang ◽  
Zhaogeng Yang ◽  
Xijie Wang ◽  
Di Gao ◽  
...  

BackgroundThe prevalence of childhood overweight and obesity in China has drastically increased 57 times over the past 30 years, and to control birth weight is an effective way to reduce the risk of overweight and obesity across the life course.ObjectiveThis paper aimed to evaluate the association of high birth weight (HBW) with overweight and obesity in Chinese students aged 6–18 years.MethodsAll students with HBW (n=4981) aged 6–18 years were selected from a cross-sectional survey from seven provinces of China, and 4981 other students with normal birth weight (NBW) were randomly sampled with matched gender, age and province. Anthropometric parameters were measured and characteristics were collected by questionnaires. Multiple logistic regression was used to estimate the OR of overweight and obesity with HBW, unadjusted and adjusted for confounding factors.ResultsParticipants with HBW revealed higher body mass index in childhood. The prevalence of overweight and obesity was significantly higher in the HBW group than in the NBW group (overweight 15.3% vs 13.1%, p<0.05; obesity 16.9% vs 10.6%, p<0.05), and the results were similar for overweight in all age groups except age 6–7, age 14–15 and age 16–18. Additionally, HBW was positively associated with overweight (OR=1.230; 95% CI 1.056 to 1.432) and obesity (OR=1.611; 95% CI 1.368 to 1.897) after adjustment for covariates.ConclusionsHBW leads to an increased risk of overweight and obesity in childhood; thus, measures to control birth weight, such as controlling gestational weight gain, should be taken from the earliest beginning of life.Trial registration numberNCT02343588; Post-results.


Reproduction ◽  
2001 ◽  
pp. 853-862 ◽  
Author(s):  
ME Symonds ◽  
H Budge ◽  
T Stephenson ◽  
IC McMillen

This article reviews the fetal endocrine system in sheep, a species that has a long gestation and primarily produces a singleton fetus. Attention is focused on information that is applicable to humans. The endocrinology of metabolic homeostasis in sheep fetuses is well adapted to respond to a range of metabolic challenges, including placental restriction and maternal undernutrition. A small placenta results in hypoxaemia, hypoglycaemia, reduced abundance of anabolic hormones, and fetal growth restriction. Fetuses with restricted growth are characterized by tissue-specific reductions in hormone receptor mRNA, for example mRNA for the long form of prolactin receptor is reduced in adipose tissue. In contrast, the adipose tissue of fetuses with accelerated growth, stimulated by increasing maternal nutrition in the second half of gestation, has more protein for the long form of the prolactin receptor and more uncoupling protein 1, by which large amounts of heat are generated at birth. Maternal undernutrition in early gestation, coinciding with the period of rapid placental growth, initially restricts placental growth, but when mothers are fed to requirements, a longer fetus results with a disproportionately large placenta. This nutritional manipulation replicates, in part, epidemiological findings from the Dutch famine of 1944-1945, for which the offspring are at increased risk of adult obesity.


2017 ◽  
Vol 312 (4) ◽  
pp. E309-E325 ◽  
Author(s):  
Pia S. Petersen ◽  
Xia Lei ◽  
Risa M. Wolf ◽  
Susana Rodriguez ◽  
Stefanie Y. Tan ◽  
...  

Chronic low-grade inflammation and cellular stress are important contributors to obesity-linked metabolic dysfunction. Here, we uncover an immune-metabolic role for C1q/TNF-related protein 7 (CTRP7), a secretory protein of the C1q family with previously unknown function. In obese humans, circulating CTRP7 levels were markedly elevated and positively correlated with body mass index, glucose, insulin, insulin resistance index, hemoglobin A1c, and triglyceride levels. Expression of CTRP7 in liver was also significantly upregulated in obese humans and positively correlated with gluconeogenic genes. In mice, Ctrp7 expression was differentially modulated in various tissues by fasting and refeeding and by diet-induced obesity. A genetic loss-of-function mouse model was used to determine the requirement of CTRP7 for metabolic homeostasis. When fed a control low-fat diet, male or female mice lacking CTRP7 were indistinguishable from wild-type littermates. In obese male mice consuming a high-fat diet, however, CTRP7 deficiency attenuated insulin resistance and enhanced glucose tolerance, effects that were independent of body weight, metabolic rate, and physical activity level. Improved glucose metabolism in CTRP7-deficient mice was associated with reduced adipose tissue inflammation, as well as decreased liver fibrosis and cellular oxidative and endoplasmic reticulum stress. These results provide a link between elevated CTRP7 levels and impaired glucose metabolism, frequently associated with obesity. Inhibiting CTRP7 action may confer beneficial metabolic outcomes in the setting of obesity and diabetes.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhaogen Yang ◽  
Bin Dong ◽  
Yi Song ◽  
Xijie Wang ◽  
Yanhui Dong ◽  
...  

Abstract Background Abdominal obesity is becoming an increasingly serious public health challenge in children and adolescents, there remains controversial opinions on birth weight and risk of childhood abdominal obesity. This study aims to assess the association between birth weight and the risk of abdominal obesity in childhood, as well as to compare the associations among different sex and age groups. Methods A total number of 30,486 (15,869 boys and 14,617 girls) participants aged 6–17 years old were included in this study. Participants were classified into five groups according to their birth weight. Waist-to-height ratio (WHtR) was used to define abdominal obesity. Fractional polynomial regression model was used to assess the association between birth weight and WHtR, and a multi-variable logistic regression model was applied to evaluate the risk of abdominal obesity in different birth weight groups. Results A J-shaped association was observed between birth weight and WHtR. Compared with birth weight of 2500–2999 g, high birth weight was associated with increased risk of abdominal obesity [OR (95% CI) for 3000–3499 g: 1.12(1.00–1.24); 3500–3999 g: 1.19(1.07–1.34); ≥4000 g: 1.42(1.24–1.62)]. No significant correlation was observed in children with birth weight ≤ 2499 g. Similar patterns were observed across different age groups. Abdominal obesity risk for high birth weight was particularly pronounced in boys compared to girls. Conclusions Birth weight ≥ 3000 g, especially for boys, was associated with an elevated risk of abdominal obesity in childhood and may benefit from intervention to mitigate this risk.


Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 584
Author(s):  
Laura Bordoni ◽  
Irene Petracci ◽  
Jean Calleja-Agius ◽  
Joan G. Lalor ◽  
Rosita Gabbianelli

Perinatal life represents a delicate phase of development where stimuli of all sorts, coming to or from the mother, can influence the programming of the future baby’s health. These stimuli may have consequences that persist throughout adulthood. Nuclear receptor related 1 protein (NURR1), a transcription factor with a critical role in the development of the dopaminergic neurons in the midbrain, mediates the response to stressful environmental stimuli in the perinatal period. During pregnancy, low-grade inflammation triggered by maternal obesity, hyperinsulinemia or vaginal infections alters NURR1 expression in human gestational tissues. A similar scenario is triggered by exposure to neurotoxic compounds, which are associated with NURR1 epigenetic deregulation in the offspring, with potential intergenerational effects. Since these alterations have been associated with an increased risk of developing late-onset diseases in children, NURR1, alone, or in combination with other molecular markers, has been proposed as a new prognostic tool and a potential therapeutic target for several pathological conditions. This narrative review describes perinatal stress associated with NURR1 gene deregulation, which is proposed here as a mediator of late-onset consequences of early life events.


Reproduction ◽  
2009 ◽  
Vol 138 (3) ◽  
pp. 609-617 ◽  
Author(s):  
P J Williams ◽  
N Marten ◽  
V Wilson ◽  
J C Litten-Brown ◽  
A M Corson ◽  
...  

Epidemiological studies suggest that low-birth weight infants show poor neonatal growth and increased susceptibility to metabolic syndrome, in particular, obesity and diabetes. Adipose tissue development is regulated by many genes, including members of the peroxisome proliferator-activated receptor (PPAR) and the fatty acid-binding protein (FABP) families. The aim of this study was to determine the influence of birth weight on key adipose and skeletal muscle tissue regulating genes. Piglets from 11 litters were ranked according to birth weight and 3 from each litter assigned to small, normal, or large-birth weight groups. Tissue samples were collected on day 7 or 14. Plasma metabolite concentrations and the expression ofPPARG2,PPARA,FABP3, andFABP4genes were determined in subcutaneous adipose tissue and skeletal muscle. Adipocyte number and area were determined histologically. Expression ofFABP3and4was significantly reduced in small and large, compared with normal, piglets in adipose tissue on day 7 and in skeletal muscle on day 14. On day 7,PPARAandPPARG2were significantly reduced in adipose tissue from small and large piglets. Adipose tissue from small piglets contained more adipocytes than normal or large piglets. Birth weight had no effect on adipose tissue and skeletal muscle lipid content. Low-birth weight is associated with tissue-specific and time-dependent effects on lipid-regulating genes as well as morphological changes in adipose tissue. It remains to be seen whether these developmental changes alter an individual's susceptibility to metabolic syndrome.


2006 ◽  
Vol 96 (2) ◽  
pp. 408-414 ◽  
Author(s):  
Elisabet Forsum ◽  
Marie Löf ◽  
Hanna Olausson ◽  
Elisabeth Olhager

Infant birth weight has increased recently, representing an obstetric and potentially a public health problem since high birth weight involves a risk of obesity later in life. Maternal nutritional status is important for fetal growth and therefore relationships between maternal body weight and composition v. birth weight and infant subcutaneous adipose tissue were investigated in twenty-three healthy women and their newborn infants using multiple and simple linear regression analysis. Furthermore, using previously published data for nineteen infants, it was demonstrated that an anthropometric method could provide useful estimates of the amount of subcutaneous adipose tissue. Birth weight was correlated with the maternal content of total body fat (TBF) both before pregnancy and in gestational week 32 and, together with gestational age at birth, TBF (%) before pregnancy explained 45% of the variation in birth weight. This figure was not increased when gestational gains in weight or TBF were added to the model. Furthermore, in infants, birth weight correlated with the amount of their subcutaneous adipose tissue. Together maternal TBF (%) and amount of subcutaneous adipose tissue in infants explained 61–63% of the variation in birth weight while the amount of infant subcutaneous adipose tissue alone explained only 55%. The maternal TBF content is likely to be important for the recent increase in birth weight. This factor probably causes a general augmentation in fetal growth rather than a specific stimulation of adipose tissue growth.


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