Erratum to: Mismatch Between Poor Fetal Growth and Rapid Postnatal Weight Gain in the First 2 Years of Life Is Associated with Higher Blood Pressure and Insulin Resistance without Increased Adiposity in Childhood: The GUSTO Cohort Study

Abstract Background Using longitudinal ultrasounds as an improved fetal growth marker, we aimed to investigate if fetal growth deceleration followed by rapid postnatal weight gain is associated with childhood cardiometabolic risk biomarkers in a contemporary well-nourished population. Methods We defined fetal growth deceleration (FGD) as ultrasound-measured 2nd-3rd-trimester abdominal circumference decrease by ≥0.67 standard deviation score (SDS) and rapid postnatal weight gain (RPWG) as 0–2-year-old weight increase by ≥0.67 SDS. In the GUSTO mother-offspring cohort, we grouped 797 children into four groups of FGD-only (14.2%), RPWG-only (23.3%), both (mismatch, 10.7%) or neither (reference, 51.8%). Adjusting for confounders and comparing with the reference group, we tested associations of these growth groups with childhood cardiometabolic biomarkers: magnetic resonance imaging (MRI)-measured abdominal fat (n = 262), liver fat (n = 216), intramyocellular lipids (n = 227), quantitative magnetic resonance-measured overall body fat % (BF%) (n = 310), homeostasis model assessment of insulin resistance (HOMA-IR) (n = 323), arterial wall thickness (n = 422) and stiffness (n = 443), and blood pressure trajectories (ages 3–6 years). Results Mean±SD birthweights were: FGD-only (3.11 ± 0.38 kg), RPWG-only (3.03 ± 0.37 kg), mismatch (2.87 ± 0.31 kg), reference (3.30 ± 0.36 kg). FGD-only children had elevated blood pressure trajectories without correspondingly increased BF%. RPWG-only children had altered body fat partitioning, higher BF% [BF = 4.26%, 95% confidence interval (CI) (2.34, 6.19)], HOMA-IR 0.28 units (0.11, 0.45)] and elevated blood pressure trajectories. Mismatch children did not have increased adiposity, but had elevated ectopic fat, elevated HOMA-IR [0.29 units (0.04,0.55)] and the highest blood pressure trajectories. Associations remained even after excluding small-for-gestational-age infants from analyses. Conclusions Fetal growth deceleration coupled with rapid postnatal weight gain was associated with elevated childhood cardiometabolic risk biomarkers without correspondingly increased BF%.

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Antenatal sildenafil citrate treatment increases offspring blood pressure in the placental-specific Igf2 knockout mouse model of FGR

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00568.2019 ◽

2020 ◽

Vol 318 (2) ◽

pp. H252-H263 ◽

Cited By ~ 2

Author(s):

L. J. Renshall ◽

E. C. Cottrell ◽

E. Cowley ◽

C. P. Sibley ◽

P. N. Baker ◽

...

Keyword(s):

Blood Pressure ◽

Weight Gain ◽

Mouse Model ◽

Systolic Blood Pressure ◽

Fetal Growth ◽

Knockout Mouse ◽

Female Offspring ◽

Sildenafil Citrate ◽

Postnatal Weight Gain

Fetal growth restriction (FGR), where a fetus fails to reach its genetic growth potential, affects up to 8% of pregnancies and is a major risk factor for stillbirth and adulthood morbidity. There are currently no treatments for FGR, but candidate therapies include the phosphodiesterase-5 inhibitor sildenafil citrate (SC). Randomized clinical trials in women demonstrated no effect of SC on fetal growth in cases of severe early onset FGR; however, long-term health outcomes on the offspring are unknown. This study aimed to assess the effect of antenatal SC treatment on metabolic and cardiovascular health in offspring by assessing postnatal weight gain, glucose tolerance, systolic blood pressure, and resistance artery function in a mouse model of FGR, the placental-specific insulin-like growth factor 2 (PO) knockout mouse. SC was administered subcutaneously (10 mg/kg) daily from embryonic day (E)12.5. Antenatal SC treatment did not alter fetal weight or viability but increased postnatal weight gain in wild-type (WT) female offspring ( P < 0.05) and reduced glucose sensitivity in both WT ( P < 0.01) and P0 ( P < 0.05) female offspring compared with controls. Antenatal SC treatment increased systolic blood pressure in both male (WT vs. WT-SC: 117 ± 2 vs. 140 ± 3 mmHg, P < 0.0001; P0 vs. P0-SC: 113 ± 3 vs. 140 ± 4 mmHg, P < 0.0001; means ± SE) and female (WT vs. WT-SC: 121 ± 2 vs. 140 ± 2 mmHg, P < 0.0001; P0 vs. P0-SC: 117 ± 2 vs. 144 ± 4 mmHg, P < 0.0001) offspring at 8 and 13 wk of age. Increased systolic blood pressure was not attributed to altered mesenteric artery function. In utero exposure to SC may result in metabolic dysfunction and elevated blood pressure in later life. NEW & NOTEWORTHY Sildenafil citrate (SC) is currently used to treat fetal growth restriction (FGR). We demonstrate that SC is ineffective at treating FGR, and leads to a substantial increase systolic blood pressure and alterations in glucose homeostasis in offspring. We therefore urge caution and suggest that further studies are required to assess the safety and efficacy of SC in utero, in addition to the implications on long-term health.

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Birthweight And Postnatal Growth As Predictors of Elevated Blood Pressure In Adolescents of Low Socioeconomic Condition: A Cohort Study In Northeast Brazil

10.21203/rs.3.rs-592145/v1 ◽

2021 ◽

Author(s):

Marcelo S Oliveira ◽

Fabiana C L S P Gonçalves ◽

Pedro I. C. Lira ◽

Sidrack L Vila Nova Filho ◽

Sophie H Eickmann ◽

...

Keyword(s):

Blood Pressure ◽

Cohort Study ◽

Weight Gain ◽

Nutritional Status ◽

Activity Level ◽

Elevated Blood Pressure ◽

Elevated Blood ◽

Rapid Weight Gain ◽

Low Socioeconomic ◽

Postnatal Weight Gain

Abstract Objective: To evaluate low birthweight and rapid postnatal weight gain as predictors of elevated blood pressure in adolescence in a population of low socioeconomic status.Methods: A cohort study was carried out with 208 adolescents, 78 born with low weight and 130 born with appropriate weight. The infants were followed up during the first six postnatal months and reassessed at 8 and 18 years of age. The main exposure variables were birth weight and weight gain in the first six postnatal months. Rapid weight gain was defined when above 0.67 z score. The investigated co-variables were: sex, maternal height and family income at birth, breastfeeding duration from birth to six months, nutritional status at eight years old, socioeconomic conditions, nutritional status, fat mass index and physical activity level at 18 years. The outcome variable was the occurrence of elevated blood pressure at 18 years old.Results: The proportion of adolescents with elevated blood pressure was 37.5%. The multivariable logistic regression analysis showed the variables independently associated with a higher chance of elevated blood pressure in adolescence were rapid postnatal weight gain (OR=2.74; 95% CI 1.22-6.14; p=0.014), male sex (OR=4.15; 95% CI 1.66-40 10.38; p=0.002) and being physically active (OR=2.70; 95% CI 1.08-6.74; p=0.034).Conclusions: The occurrence of rapid weight gain in the first six postnatal months was a predictor for elevated blood pressure in adolescence. This result highlights the influence of factors related to development in early childhood on health problems in the future.

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Voluntary wheel running is effective on suppressing of obesity but not on blood pressure and insulin resistance in female rats fed with high fructose diet

Trakia Journal of Sciences ◽

10.15547/tjs.2021.01.004 ◽

2021 ◽

Vol 19 (1) ◽

pp. 21-28

Author(s):

P. Tayfur ◽

K. Gökçe Tezel ◽

Ö. Barutçu ◽

S. Yılmaz ◽

E. Ö. Özgür ◽

...

Keyword(s):

Physical Activity ◽

Insulin Resistance ◽

Blood Pressure ◽

Body Weight ◽

Weight Gain ◽

Wheel Running ◽

Female Rats ◽

Walking Distance ◽

Voluntary Activity ◽

Voluntary Physical Activity

A fructose-rich diet has been known to cause metabolic syndrome effects such as body weight gain, increased blood pressure, blood lipids and glucose levels. The role of voluntary physical activity in these alterations is not known clearly. The aim of this study was to investigate the possible improving effects of voluntary physical activity in rats that were feeding with a fructose-rich diet. Spraque-Dawley female rats were separated as control (C;n=7), voluntary physical activity (A;n=7), fructose (F;n=7) and fructose+activity (F+A;n=7) groups. A and FA groups were kept in cages with running wheels during six weeks. F and FA groups were fed with adding 20% fructose in drinking water. Body weight was measured weekly and Lee Index was used to determine obesity. At the end of the feeding period serum glucose, insulin and lipid levels were measured by enzymatic method and blood pressure was determined with the tail-cuff method. Daily voluntary walking distance in F+A and A groups were similar during six weeks. Fructose intake induced to increase systolic blood pressure (p=0.001), diastolic blood pressure (p=0.002), glucose (p=0.041), insulin (p=0.001), cholesterol (p=0.001), triglyceride (p=0.001) and liver weight (p=0.035). The voluntary activity was found effective on the decrease of weight gain (p=0.018) however we did not observe a significant effect on blood pressure (p=0.917) and insulin resistance (p=0.565) following the fructose-rich diet. We conclude that voluntary activity has preventive effect on obesity but may not to be effective on increased blood pressure and insulin resistance in female rats which were feeding fructose-rich diet during six weeks.

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Abstract 015: Increased 20-HETE Levels Contribute to Impaired Glucose Metabolism and Type 2 Diabetes in Cyp4a14 Knockout Mice Fed on High Fat Diet.

Hypertension ◽

10.1161/hyp.66.suppl_1.015 ◽

2015 ◽

Vol 66 (suppl_1) ◽

Author(s):

Varunkumar G Pandey ◽

Lars Bellner ◽

Victor Garcia ◽

Joseph Schragenheim ◽

Andrew Cohen ◽

...

Keyword(s):

Insulin Resistance ◽

Blood Pressure ◽

Type 2 Diabetes ◽

Weight Gain ◽

Blood Glucose ◽

High Fat Diet ◽

Plasma Insulin ◽

High Fat ◽

Plasma Insulin Levels

20-HETE (20-Hydroxyeicosatetraenoic acid) is a cytochrome P450 ω-hydroxylase metabolite of arachidonic acid that promotes endothelial dysfunction, microvascular remodeling and hypertension. Previous studies have shown that urinary 20-HETE levels correlate with BMI and plasma insulin levels. However, there is no direct evidence for the role of 20-HETE in the regulation of glucose metabolism, obesity and type 2 diabetes mellitus. In this study we examined the effect of 20-SOLA (2,5,8,11,14,17-hexaoxanonadecan-19-yl-20-hydroxyeicosa-6(Z),15(Z)-dienoate), a water-soluble 20-HETE antagonist, on blood pressure, weight gain and blood glucose in Cyp4a14 knockout (Cyp4a14-/-) mice fed high-fat diet (HFD). The Cyp4a14-/- male mice exhibit high vascular 20-HETE levels and display 20-HETE-dependent hypertension. There was no difference in weight gain and fasting blood glucose between Cyp4a14-/- and wild type (WT) on regular chow. When subjected to HFD for 15 weeks, a significant increase in weight was observed in Cyp4a14-/- as compared to WT mice (56.5±3.45 vs. 30.2±0.7g, p<0.05). Administration of 20-SOLA (10mg/kg/day in drinking water) significantly attenuated the weight gain (28.7±1.47g, p<0.05) and normalized blood pressure in Cyp4a14-/- mice on HFD (116±0.3 vs. 172.7±4.6mmHg, p<0.05). HFD fed Cyp4a14-/- mice exhibited hyperglycemia as opposed to normal glucose levels in WT on a HFD (154±1.9 vs. 96.3±3.0 mg/dL, p<0.05). 20-SOLA prevented the HFD-induced hyperglycemia in Cyp4a14-/- mice (91±8mg/dL, p<0.05). Plasma insulin levels were markedly high in Cyp4a14-/- mice vs. WT on HFD (2.66±0.7 vs. 0.58±0.18ng/mL, p<0.05); corrected by the treatment with 20-SOLA (0.69±0.09 ng/mL, p<0.05). Importantly, glucose and insulin tolerance tests showed impaired glucose homeostasis and insulin resistance in Cyp4a14-/- mice on HFD; ameliorated by treatment with 20-SOLA. This novel finding that blockade of 20-HETE actions by 20-SOLA prevents HFD-induced obesity and restores glucose homeostasis in Cyp4a14-/- mice suggests that 20-HETE contributes to obesity, hyperglycemia and insulin resistance in HFD induced metabolic disorder. The molecular mechanisms underlying 20-HETE mediated metabolic dysfunction are being currently explored.

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