Obesity In Offspring Research Articles

Perinatal Fat-Diets Increased Angiotensin II-Mediated Ca2+ through PKC-L-Type Calcium Channel Axis in Resistance Arteries via Agtr1a-Prkcb Gene Methylation.

Perinatal malnutrition affects vascular functions, and calcium is important in vascular regulations. It is unknown whether and how perinatal maternal high-fat diets (MHF)-mediated vascular dysfunction occurs via the angiotensin-PKC-L-type-calcium-channels (LTCC) axis. This study determined angiotensin II (AII) roles in the PKC-LTCC axis in controlling calcium influx in the arteries of offspring after perinatal MHF. Mesenteric arteries (MA) and smooth muscle cells (SMCs) from 5-month-old offspring rats were studied using physiological, ion channel, molecular, and epigenetic analysis. Pressor responses to AII were significantly increased in the free-moving MHF offspring rats. In cell experiments, MA-SMC proliferation was enhanced, and associated with thicker vascular wall in the obese offspring. Imaging analysis showed increase of fluorescence Ca2+ intensity in the SMCs of the MHF group. Angiotensin II receptor (AT1R)-mediated PKC-LTCC axis in vasoconstrictions was altered by perinatal MHF via reduced DNA methylation at specific CpG sites of Agtr1a and Prkcb gene promoters at the transcription level. Accordingly, mRNA and protein expression of AT1R and PKCβ in the offspring MA were increased, contributing to enhanced Ca2+ currents and vascular tone. The results showed that DNA methylation resulted in perinatal MHF-induced vascular disorders via altered AT1-PKC-LTCC pathway in resistance arteries of the offspring, providing new insights into the pathogenesis and early prevention/treatments for hypertension in developmental origins.

Maternal bariatric surgery: a sibling-matched analysis comparing health of offspring born before and after surgery

Due to the global escalation in the prevalence of obesity, bariatric surgeries have become a popular solution in many western countries. The aim of the current study was to compare offspring health and obesity of women before and after undergoing bariatric surgeries. A retrospective population based study was performed, including all singleton deliveries which occurred at a tertiary medical center between the years 1991-2021. Among women who had bariatric surgeries, health of the offspring born before and after the surgery were compared. The offspring were followed-up until the age of 18 years, and their hospitalization records were summarized. The incidence of hospitalization with either endocrine, cardiac, respiratory, neurologic or infectious diagnoses were compared between the groups, as well as offspring obesity. Multivariable Cox proportional models were used to match between siblings and to address confounding variables, including maternal age, gestational age at delivery, fertility treatment, smoking and pregnancy hypertensive disorders. The study population included 380,258 deliveries, 3,074 were of women who underwent bariatric surgeries (1,586 were before and 1,488 after the surgery). Offspring born after maternal bariatric surgeries were at a comparable risk for most morbidities (Table), besides endocrine related morbidities (3.2% vs. 5.2%, OR=1.68; 1.17-2.41) and obesity (2.5% vs. 4.1%, OR=1.61; 1.08-2.41). The risk for these morbidities was higher among offspring of mothers after versus before the surgery, although adjustment for maternal age and other confounding variables (Graph). While bariatric surgeries are considered an effective treatment for obesity, it seems to have less effect on offspring of women who underwent such surgeries. Other persistent factors are most likely associated with the offspring risk for morbidities, especially endocrine morbidities and obesity, which remain although the mother underwent bariatric surgeries.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Maternal Polycystic Ovary Syndrome and the Risk of Early Childhood Obesity in Female Offspring: A Nationwide Population-Based Study.

To investigate the relationship between polycystic ovary syndrome (PCOS) in Korean women and childhood growth and obesity of their offspring. This longitudinal case-control study using the Korean National Health Insurance claims database and the National Health Screening Program for Infants and Children database included women who delivered singletons between January 2007 and December 2008. Offspring's body mass index (BMI) measurements taken between 42 and 80 months of age were compared according to a maternal history of PCOS. Among a total of 131,805 participants, 1,213 women had a history of PCOS and 130,592 women did not. Female offspring aged 66-80 months born to women with PCOS had significantly higher BMI than those born to women without PCOS; there was no significant difference in that of male offspring regardless of maternal PCOS. In the generalized estimating equation and multivariable logistic regression analyses, the female offspring born to women with PCOS had a significantly higher risk of obesity during the age of 42-54 and 66-80 months (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.09-2.21 and OR, 1.5; 95% CI, 1.05-2.15, respectively), than those born to women without PCOS, after adjusting for several confounding factors. Maternal PCOS is independently associated with an increased incidence of childhood obesity in female offspring among Korean women. Women with PCOS should consider the risk of early childhood obesity in their daughters, even if they maintain a healthy weight themselves.

Maternal obesity: Perinatal implications.

Over the previous three decades, the prevalence and growth of overweight and obese status has risen relentlessly in both the general population and pregnant women. This rise is seen in both higher pre-pregnancy body mass index measurements along with excessive weight gain during pregnancy. Maternal obesity has been shown to exacerbate co-morbidities such as insulin resistance, pregnancy induced hypertension, and infectious states in parturient mothers. These changes have been shown to subsequently increase rates of fetal anomalies and affect fetal growth, as well as various aspects of the delivery such as rates of instrumented vaginal deliveries and an increase in delivery by cesarean section. Maternal obesity increases fetal birth weight, influences the delivery room resuscitation of the neonate by increasing the need for respiratory support, and increases the risk of neonatal hypoxic ischemic encephalopathy. This review also looks at recent studies revealing the strong association between maternal and offspring obesity and other long-term neurodevelopmental outcomes of offspring.

Women with gestational diabetes mellitus controlled for their plasma glucose levels, exhibit dyslipidaemia that may contribute to offspring obesity and the risk of future gestational diabetes mellitus

Women with gestational diabetes mellitus controlled for their plasma glucose levels, exhibit dyslipidaemia that may contribute to offspring obesity and the risk of future gestational diabetes mellitus - Volume 82 Issue OCE2

Intergenerational Transmission of Obesity: Role of Education and Income

Based on the sixth round of the 2018 Chinese Household Income Project family income survey (CHIP) data, this study made use of the OLS estimation and transfer matrix method to measure and test the problem of obesity intergenerational transmission, analyze whether there is obesity intergenerational transmission as well as between urban and rural areas, gender, and the parental education level and income level on the suppression of the obesity intergenerational transmission effect. The empirical results draw the following main conclusions: obesity intergenerational transmission in Chinese families, the degree of parental obesity has a significant positive impact on the degree of offspring obesity; the higher the degree of parental obesity, the more it can promote the degree of obesity in the offspring. Moreover, the degree of obesity intergenerational transmission is heterogeneous in urban and rural areas and gender. At the same time, the degree of rural obesity intergenerational transmission is higher than that of urban areas, and the degree of male obesity intergenerational transmission is higher than that of women.

Prenatal metabolomic profiles mediate the effect of maternal obesity on early childhood growth trajectories and obesity risk: the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) Study

Maternal prepregnancy obesity is an important risk factor for offspring obesity, which may partially operate through prenatal programming mechanisms. The study aimed to systematically identify prenatal metabolomic profiles mediating the intergenerational transmission of obesity. We included 450 African American mother-child pairs from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood Study (CANDLE) pregnancy cohort. Liquid chromatography-mass spectrometry was used to conduct metabolomic profiling on the maternal plasma samples of the second trimester. The childhood growth outcomes of interest included body mass index (BMI) trajectories from birth to age 4 (rising-high-, moderate-, and low-BMI trajectories) as well as overweight/obesity (OWO) risk at age 4. Mediation analysis was conducted to identify metabolite mediators linking maternal OWO and childhood growth outcomes. The potential causal effects of maternal OWO on metabolite mediators were examined using the Mendelian Randomization (MR) method. Among 880 metabolites detected in the maternal plasma during pregnancy, 14 and 11 metabolites significantly mediated the effects of maternal prepregnancy OWO on childhood BMI trajectories and the OWO risk at age 4, respectively, and five of those mediated both outcomes. The MR analysis suggested six of the 20 prenatal metabolite mediators might be causally influenced by maternal prepregnancy OWO, most of which are from the pathways related to the metabolism of amino acids (hydroxyasparagine, glutamate, and homocitrulline), sterols (campesterol), and nucleotides (N2, N2-dimethylguanosine). Our study provided further evidence that prenatal metabolomic profiles might mediate the effect of maternal OWO on early childhood growth trajectories and OWO risk in offspring. The metabolic pathways including identified metabolite mediators might provide novel intervention targets for preventing the intrauterine development of obesity in offspring of mothers with obesity.

Maternal inappropriate calcium intake aggravates dietary-induced obesity in male offspring by affecting the differentiation potential of mesenchymal stem cells.

The effects of inappropriate dietary calcium intake in early life on later obesity have not been fully elucidated. To raise the mechanism of maternal calcium intake on the multi-differentiation potential of mesenchymal stem cells among their male offspring. Four-week-old female C57BL/6N mice were fed by deficient, low, normal and excessive calcium reproductive diets throughout pregnancy and lactation. Bone MSCs (BMSCs) were obtained from 7-day-old male offspring to measure the adipogenic differentiation potential by the Wnt/β-catenin signaling pathway. The other weaning male pups were fed a high-fat diet for 16 wk, along with normal-fat diet as the control. Then the serum was collected for the measurement of biochemical indicators. Meanwhile, the adipose tissues were excised to analyze the adipocyte sizes and inflammatory infiltration. And the target gene expressions on the adipogenic differentiation and Wnt/β-catenin signaling pathway in the adipose tissues and BMSCs were determined by real-time reverse transcription polymerase chain reaction. Compared with the control group, maternal deficient, low and excessive calcium intake during pregnancy and lactation aggravated dietary-induced obesity, with larger adipocytes, more serious inflammatory infiltration and higher serum metabolism indicators by interfering with higher expressions of adipogenic differentiation (PPARγ, C/EBPα, Fabp4, LPL, Adiponectin, Resistin and/or Leptin) among their male offspring (P < 0.05). And there were significantly different expression of similar specific genes in the BMSCs to successfully polarize adipogenic differentiation and suppress osteogenic differentiation in vivo and in vitro, respectively (P < 0.05). Meanwhile, it was accompanied by more significant disorders on the expressions of Wnt/β-catenin signaling pathway both in BMSCs and adulthood adipose tissues among the offspring from maternal inappropriate dietary calcium intake groups. Early-life abnormal dietary calcium intake might program the adipogenic differentiation potential of BMSCs from male offspring, with significant expressions on the Wnt/β-catenin signaling pathway to aggravate high-fat-diet-induced obesity in adulthood.

The influence of perinatal maternal exposure to dibutyl phthalate on glucolipid metabolism in adult female offspring

BackgroundMaternal exposure to dibutyl phthalate (DBP) may result in obesity in female offspring. However, the underlying mechanisms remain elusive. Materials and methodsSprague-Dawley rats were intraperitoneally injected with different doses of DBP and corn oil from gestational day 7 until the end of lactation. The weights, visceral fat percentage, serum lipid, insulin and glucose, protein levels of PI3K signal pathway in muscle were detected in F1 female offspring. ResultsAlthough the birth weight of F1 female offspring was not different among groups, the weights were heavier in DBP groups from postnatal day 7 to adult (P < 0.001). The visceral adipose percentage in adult female offspring was increased by perinatal exposure to DBP (P < 0.001). Decreased serum level of triglyceride (P = 0.001) in F1 female offspring was found in DBP group as compared to control, especially in medium and high DBP. However, none difference was found for fasting glucose, prolactin, HOMA-IR, fasting insulin, total cholesterol, adiponectin. Different protein levels of GPR30 were observed in muscle of female offspring among four groups (P = 0.016). The protein level of AKT seemed higher in DBP group but without statistical significance (P = 0.05). None difference was observed for the protein levels of PI3K, p-AKT, pAKT/AKT, PTEN, GLUT4, InsR, IRS. ConclusionMaternal perinatal exposure to DBP might induce obesity and accumulation of visceral adipose tissue for the adult female offspring. Serum glucolipid and local signal transduction of PTEN/PI3K/AKT pathway in muscle were not adversely affected by perinatal exposure to DBP for adult female offspring.

Maternal consumption of ultra-processed foods and subsequent risk of offspring overweight or obesity: results from three prospective cohort studies

ObjectiveTo assess whether maternal ultra-processed food intake during peripregnancy and during the child rearing period is associated with offspring risk of overweight or obesity during childhood and adolescence.DesignPopulation based prospective...

Molecular programming modulates hepatic lipid metabolism and adult metabolic risk in the offspring of obese mothers in a sex-specific manner

Male and female offspring of obese mothers are known to differ extensively in their metabolic adaptation and later development of complications. We investigate the sex-dependent responses in obese offspring mice with maternal obesity, focusing on changes in liver glucose and lipid metabolism. Here we show that maternal obesity prior to and during gestation leads to hepatic steatosis and inflammation in male offspring, while female offspring are protected. Females from obese mothers display important changes in hepatic transcriptional activity and triglycerides profile which may prevent the damaging effects of maternal obesity compared to males. These differences are sustained later in life, resulting in a better metabolic balance in female offspring. In conclusion, sex and maternal obesity drive differently transcriptional and posttranscriptional regulation of major metabolic processes in offspring liver, explaining the sexual dimorphism in obesity-associated metabolic risk.

Association between maternal erythrocyte polyunsaturated fatty acid levels during pregnancy and offspring weight status: A birth cohort study.

BackgroundThe findings of the association between maternal polyunsaturated fatty acid (PUFA) levels during pregnancy and offspring weight status are controversial. Furthermore, few studies have focused on Asian populations or used erythrocyte membranes as biological markers. We aimed to examine the associations between maternal erythrocyte PUFA and offspring weight status within the first 2 years among the Chinese population.Materials and methodsA total of 607 mother-child pairs were recruited from a birth cohort. Maternal erythrocyte n-3 and n-6 PUFA during pregnancy were measured by gas chromatography, and the ratio of PUFA was calculated. Weight- and body mass index (BMI)-for-age z (WAZ and BAZ) scores were calculated for offspring at 1, 3, 6, 8, 12, 18, and 24 months of age. The risk of overweight and obesity was defined by the WHO criterion. The Generalized Estimating Equation (GEE) model was carried out for repeated anthropometric data within 2 years of age.ResultsMaternal erythrocyte docosapentaenoic acid (DPA, n-3) was inversely associated with offspring BAZ score [tertile 2 vs. tertile 1, β: −0.18 (−0.29, −0.00)]. Higher maternal erythrocyte arachidonic acid (AA) was inversely associated with lower offspring WAZ and BAZ [tertile 3 vs. tertile 1, β: −0.18 (−0.35, −0.02), −0.22 (−0.38, −0.06), respectively]. Furthermore, higher maternal erythrocyte AA [tertile 3 vs. tertile 1, odds ratio [OR]: 0.52 (0.36, 0.75), ptrend < 0.001] and total n-6 PUFA [tertile 3 vs. tertile 1, OR: 0.56 (0.39, 0.81), ptrend = 0.002] were associated with decreased risk of overweight and obesity in offspring. Maternal erythrocyte n-6/n-3 PUFA and AA/eicosapentaenoic acid (EPA) ratios were not associated with offspring weight status.ConclusionMaternal erythrocyte PUFA might influence offspring weight status within 2 years of age in the Chinese population. Further Asian studies are still needed.

Female and male C57BL/6J offspring exposed to maternal obesogenic diet develop altered hypothalamic energy metabolism in adulthood.

Maternal obesity is exceedingly common and strongly linked to offspring obesity and metabolic disease. Hypothalamic function is critical to obesity development. Hypothalamic mechanisms causing obesity following exposure to maternal obesity have not been elucidated. Therefore, we studied a cohort of C57BL/6J dams, treated with a control or high-fat-high-sugar diet, and their adult offspring to explore potential hypothalamic mechanisms to explain the link between maternal and offspring obesity. Dams treated with obesogenic diet were heavier with mild insulin resistance, which is reflective of the most common metabolic disease in pregnancy. Adult offspring exposed to maternal obesogenic diet had no change in body weight but significant increase in fat mass, decreased glucose tolerance, decreased insulin sensitivity, elevated plasma leptin, and elevated plasma thyroid-stimulating hormone. In addition, offspring exposed to maternal obesity had decreased energy intake and activity without change in basal metabolic rate. Hypothalamic neurochemical profile and transcriptome demonstrated decreased neuronal activity and inhibition of oxidative phosphorylation. Collectively, these results indicate that maternal obesity without diabetes is associated with adiposity and decreased hypothalamic energy production in offspring. We hypothesize that altered hypothalamic function significantly contributes to obesity development. Future studies focused on neuroprotective strategies aimed to improve hypothalamic function may decrease obesity development.NEW & NOTEWORTHY Offspring exposed to maternal diet-induced obesity demonstrate a phenotype consistent with energy excess. Contrary to previous studies, the observed energy phenotype was not associated with hyperphagia or decreased basal metabolic rate but rather decreased hypothalamic neuronal activity and energy production. This was supported by neurochemical changes in the hypothalamus as well as inhibition of hypothalamic oxidative phosphorylation pathway. These results highlight the potential for neuroprotective interventions in the prevention of obesity with fetal origins.

Abstracts from the NIH Office of Research on Women's Health 2022 Annual BIRCWH Meeting:Building Interdisciplinary Research Careers in Women's Health November 2, 2022

Abstracts from the NIH Office of Research on Women's Health 2022 Annual BIRCWH Meeting:Building Interdisciplinary Research Careers in Women's Health November 2, 2022

How Do the Different Types of Maternal Diabetes during Pregnancy Influence Offspring Outcomes?

Background/Aim of the study: Exposure to maternal diabetes is considered one of the most common in utero insults that can result in an increased risk of complications later in life with a permanent effect on offspring health. In this study, we aim to assess the level of risk associated with each type of maternal diabetes on obesity, glucose intolerance, cardiovascular diseases (CVD), and neurodevelopmental disorders in offspring. Methods: We conducted a systematic review of the literature utilizing PubMed for studies published between January 2007 and March 2022. Our search included human cohorts and case control studies following offspring exposed at least to two different types of maternal diabetes clearly identified during pregnancy. Collected outcomes included prevalence, incidence, odds ratio, hazard ratio and risk ratio. Results: Among 3579 published studies, 19 cohorts were eligible for inclusion in our review. The risks for overweight, obesity, type 2 diabetes (T2D), glucose intolerance, metabolic syndrome, and CVD were increased for all types of maternal diabetes during pregnancy. The risk of overweight or obesity in infancy and in young adults was similar between gestational diabetes mellitus (GDM) and type 1 diabetes (T1D). The risk for T2D or abnormal glucose tolerance was double for offspring from GDM mothers compared to offspring from T1D mothers. In contrast, the risk for T1D in offspring at any age until young adulthood was increased when mothers had T1D compared to GDM and T2D. The risk for CVD was similar for all types of maternal diabetes, but more significant results were seen in the occurrence of heart failure and hypertension among offspring from T2D mothers. The risk of autism spectrum disorders and attention deficit/hyperactivity disorders was mainly increased after in utero exposure to preexisting T1D, followed by T2D. Conclusions: Offspring of diabetic mothers are at increased risk for multiple adverse outcomes with the highest risk detected among offspring from T2D mothers. Future work warrants large multiethnic prospective cohort studies that aim to identify the risks associated with each type of maternal diabetes separately.

A prospective cohort study of the association between key family and individual factors and obesity status among youth

There remains a significant gap in our knowledge of the synergistic nature of family dynamics, child characteristics, and child-rearing features in the etiology of obesity from childhood through adolescence. We assessed the associations of family dynamics (poverty, family structure), child characteristics (child temperament), and child-rearing features (maternal depression, maternal sensitivity, and type of child care) with the development of childhood obesity. Children (n = 1240) whose weights and heights were measured at least once for ten time points (from 2 years through 15 years) from the NICHD Study of Early Child Care and Youth Development were included. Generalized estimating equation (GEE) was used to examine the associations of family and individual factors with the childhood obesity after adjusting for covariates. Adjusted GEE models showed that living below poverty level was associated with an increased odds of obesity (odds ratio = 1.62, 95% confidence interval 1.05, 2.53). Among these key family and individual factors, poverty status was observed to be the strongest predictor of obesity of offspring across time. Findings highlight the importance of systemic-level public health changes in obesity reduction efforts and suggest that poverty-reduction based prevention and intervention are likely more effective targets than more individual/family specific targets.

Early life dietary emulsifier exposure predisposes the offspring to obesity through gut microbiota-FXR axis

The prevalence of obesity is increasing rapidly around the world, and there is growing evidence that obesity is closely related to diet and gut microbiota. Early life adverse exposures have profound effects on gut microbiota. However, the effects of maternal emulsifier polysorbate 80 (P80) exposure in early life on obesity of offspring remains unclear. Female C57BL/6 mice were free access to water containing 1 % P80 during pregnancy and lactation to investigate the effects of maternal P80 exposure on gut microbiota and obesity susceptibility of offspring, while bile acid composition and the FGF15-FXR axis were also analyzed. Maternal P80 exposure significantly impaired intestinal development and barrier function and increased intestinal low-grade inflammation in offspring mice. Maternal P80 exposure led to gut dysbiosis in offspring at 3 weeks of age, which was characterized by increased potentially harmful bacteria, Prevotella, Helicobacter and Ruminococcus and Mucin degrading bacteria, Akkermansia. Interestingly, mice transplanted with the fecal microbiota of offspring exposed to maternal P80 showed more serious intestinal barrier impairment and increased low-grade inflammation than that received microbiota of offspring fed with normal diet. After a high-fat diet, Maternal P80 exposed offspring showed more severe in gut dysbiosis and obesity, accompanied by alternation in bile acid profile and up regulation of the FXR-FGF15 axis. Conclusively, early life emulsifier exposure predisposes the offspring to obesity through gut microbiota-FXR axis. The findings will provide new insights into effects of P80 on health.

Maternal programming by high-energy diets primes ghrelin sensitivity in the offspring of rats exposed to chronic immobilization stress

Maternal overnutrition during pregnancy leads to metabolic and immune alterations, including obesity, hyperphagia, and central and peripheral inflammation in offspring. Exposure to high-energy diets during pregnancy primes ghrelin sensitivity to overfeeding in the offspring at early stages of life. Overfeeding has also been partially related to the early stages of chronic stress. We hypothesized that maternal programming sensitizes ghrelin-induced overfeeding following a chronic stress schedule in the offspring. We used a nutritional programming model exposing female Wistar rats to a cafeteria (CAF) or control diet from prepregnancy to weaning. Male offspring were injected with ghrelin and then subjected to a chronic immobilization stress (CIS) schedule, after which food intake was determined. Hypothalamic and plasma accumulation of cytokines and cortisol were evaluated using BioPlex analysis and enzyme-linked immunosorbent assay, respectively. We found that rats exposed to the CAF diet exhibited overfeeding after fasting and peripheral ghrelin administration, which was exacerbated in rats exposed to chronic stress. Offspring exposed to the CAF diet accumulated pro-inflammatory interleukin-6 (IL-6), interferon-γ, and monocyte chemoattractant protein-1 cytokines in plasma, and IL-6 cytokine in the hypothalamus. Ghrelin-sensitive overfeeding in rats exposed to CAF diet + CIS display increased cortisol levels and decreased IL-6 accumulation in plasma. Together, our results suggest that maternal nutritional programming primes susceptibility to ghrelin response for overfeeding after a CIS schedule that mirrors plasma cortisol accumulation in male offspring.

Growth patterns among late preterm infants of mothers with diabetes

Objective Exposure to diabetes mellitus during pregnancy increases the risk of offspring obesity and cardiometabolic disease. Limited information exists regarding growth patterns among preterm infants exposed to maternal diabetes. This study describes growth differences during early childhood among late preterm infants of mothers with and without diabetes during pregnancy. Materials and methods In a retrospective longitudinal analysis, weight trajectories from birth to age 2 years were compared between diabetes exposure groups (N = 1554) using mixed effects modeling and adjusting for maternal and infant demographic covariates. Results Overall, 134 (9%) infants were exposed to diabetes (DM-group). DM-group had higher average weight (adjusted difference 300 g [95% CI: 228, 371]) and weight z-score (adjusted difference 0.67 standard deviation scores (SDS) [95% CI: 0.50, 0.84]) compared with unexposed infants. DM-group infants had accelerated weight gain from birth to discharge (adjusted weight difference 31.8 g [95% CI: 12.5, 51.1], adjusted weight z-score difference 0.07 SDS [95% CI: 0.02, 0.11]) compared with unexposed infants, including in the first postnatal week (adjusted weight gain velocity difference, day 0–3: 6.07 g/day [95% CI: 0.88, 11.25]; day 3–7: 8.37 g/day [95% CI: 1.60, 15.13]). Through age two, infants in the DM-group maintained higher average weight (adjusted difference 185.7 g [95% CI: 37.2, 334.3]) and weight z-score (adjusted difference 0.32 SDS [95% CI: 0.09, 0.55]) than unexposed infants, with greater weight gain between 18 and 24 months (adjusted difference 28.5 g/week [95% CI: 2.6, 54.4]). Conclusions Maternal diabetes exposed late preterm infants had higher weight from birth to age two and greater weight gain in the first postnatal week than unexposed infants. Long term risk associated with weight trajectories in this population requires further study.

Abstract 112: Role Of Endogenous Brain Melanocortin-4 Receptor Activation In Regulating Blood Pressure And Metabolic Function In Offspring Of Parents With Obesity

We previously demonstrated that activation of the central nervous system (CNS) melanocortin system modulates sympathetic nerve activity (SNA) and blood pressure (BP) in obese Zucker rats and spontaneously hypertensive rats (SHRs). In the present study, we examined whether endogenous activation of the brain melanocortin-4 receptors (MC4R) contributes to the regulation of BP and metabolic function in adult male (24-26 weeks-old) obese and lean offspring from parents fed a normal (N) or high fat diet (H). The rats were implanted with telemetry probes to measure BP and heart rate (HR) 24-hrs/day, and an intracerebroventricular (ICV) cannula was placed into the lateral ventricle. After 1 week to recover from surgery and 2 days of control measurements, the MC4R antagonist (SHU-9119) was infused (1 nmol/h, ICV) for 7 days followed by a 7-day recovery period. MC4R antagonism markedly increased food intake in all groups; however, the increase was more pronounced in obese offspring from obese H-fed parents (HH), especially when analyzing the net cumulative increase in food intake during the 7 days of treatment (191±11 vs. 136±14, 65±18 and 72±12 g) compared with obese offspring from lean N-fed parents (NH), lean offspring from obese H-fed parents (HN) and lean offspring from lean parents (NN), respectively. This increased food intake was associated with more weight gain in HH compared with NH, HN and NN offspring (Δ: 92±12 vs. 81±17, 52±11 and 38±9 g). Plasma leptin and insulin levels were markedly increased in HH offspring compared to NH, HN and NN offspring. Compared to NH and NN offspring from lean parents, HH and HN offspring from obese parents exhibited higher baseline mean arterial pressure (125±2 and 122±3 vs. 118±1 and 113±3 mmHg) and greater reduction in BP during SHU-9119 infusion (average last 3 days of infusion: -14.3±0.1 and -5.6±0.5 vs. -9.8±0.2 and -3.4±0.2 mmHg, respectively). The reduction in HR during SHU-9119 infusion, however, was more pronounced in NH and NN groups compared with HH and HN offspring (average last 3 days of infusion: -55±2 and -43±1 vs. -34±2 and -34±1 bpm). These results suggest that endogenous activation of brain MC4R may contribute to the elevated BP in obese offspring but not lean offspring from obese parents.