Hepatic and Skeletal Muscle Autophagy Marker Levels in Rat Models of Prenatal and Postnatal Protein Restriction.

Fetal growth restriction (FGR) leads to adult-onset metabolic syndrome. Intrauterine and early postnatal caloric restriction ameliorates the risk in animal models. To understand the underlying mechanism, we compared autophagic marker levels between offspring with FGR and those with prenatal and early postnatal protein restriction (IPPR). We postulated that FGR would impair, whereas IPPR would help regulate, autophagy in neonatal rats. This study involved control (Con), FGR offspring (Pre), and IPPR offspring groups (Pre + Post); n = 5/group. We assessed the abundance of autophagy markers in the liver and skeletal muscles. At birth, the Pre group pups had lower levels of some autophagy-related proteins, with increased p62 expression and a low microtubule-associated protein light chain beta (LC3-II:LC3-I) ratio. This finding suggests a lower hepatic autophagy flux in FGR offspring than the Con group. The hepatic levels of autophagy proteins were considerably decreased in the Pre and Pre + Post groups at 21 days of age compared to the Con group, but the LC3-II:LC3-I ratio was higher in the Pre + Post group than in the Con and Pre groups. The muscle levels of beclin-1, LC3-II, and p62 were lower in the Pre group pups, with no difference in the LC3-II:LC3-I ratio among the groups. An imbalance in the nutritional environment is associated with downstream autophagic flux, thus suggesting that FGR offspring will have impaired autophagic flux, and that post-natal nutrition restriction might help reduce this risk.

Effects of Fetal Growth Restriction on Postnatal Gut Microbiota in a Rat Model.

OBJECTIVE: Fetal growth restriction (FGR) indicates increased risks of lifestyle-related diseases in adulthood. Previous studies showed the association between human gut dysbiosis and various diseases. However, reports examining the relationship between FGR and gut microbiota are scarce. Herein, we hypothesized that FGR may cause gut dysbiosis and analyzed the gut microbiota in a FGR rat model by restricting maternal protein intake during pregnancy. METHODS: The FGR group was developed by feeding pregnant Sprague Dawley rats a diet containing 7% protein until birth. Control rats were fed 21% protein. Fecal samples of 2-11-week-old pups were collected weekly. DNA was extracted from each sample and subjected to polymerase chain reaction (PCR) amplification and sequencing. Additionally, short-chain fatty acids in the cecum were analyzed at 2 weeks of age, when there were differences in the occupancy of the gut microbiota. RESULTS: Comparative analysis of the gut microbiota showed differences only at 2 weeks of age. Verrucomicrobia was significantly more abundant in the control group ( q < 0.1), whereas pathogenic bacteria, including Enterococcus and Enterobacteriaceae , tended to increase in the FGR group. The abundance of acetic and butyric acid-producing bacteria also differed between groups. Acetic acid in the cecum was considerably decreased in the FGR group, while butyric acid was increased compared to that in the control group. CONCLUSIONS: Normalizing the alteration of FGR on postnatal gut microbiota may have beneficial effects for the host, since the FGR group caused gut dysbiosis.

Skeletal Muscle Insulin Resistance in a Novel Fetal Growth Restriction Model.

The abnormal fetal environment exerts long-term effects on skeletal muscle, and fetal growth restriction (FGR) is associated with insulin resistance in adulthood. In this study, we examined insulin resistance in early adulthood and insulin signaling in skeletal muscle using a novel FGR rat model. Ameroid constrictors (AC) were placed on the bilateral uterine and ovarian arteries of rats on day 17 of gestation; placebo surgery was performed on the control group. We measured body weight at birth, 4, 8, and 12 weeks of age and performed oral glucose tolerance tests at 8 and 12 weeks. Rats were dissected at 12 weeks of age. We examined the mRNA and protein expression of insulin signaling pathway molecules in skeletal muscle. FGR rats had a significantly lower birth weight than control rats (p = 0.002). At 12 weeks of age, the incremental area under the curve of blood glucose was significantly higher, and GLUT4 mRNA and protein expression in soleus muscle was significantly lower in the FGR group than in the control group. Reduced placental blood flow in the AC-attached FGR group caused insulin resistance and altered insulin signaling in skeletal muscles. Therefore, FGR causes skeletal muscle insulin resistance in early adulthood.

Evaluation of the use of non-invasive hemoglobin measurement in early childhood.

BACKGROUND: Iron deficiency anemia in children affects psychomotor development. We compared the accuracy and trend of a non-invasive transcutaneous spectrophotometric estimation of arterial hemoglobin (Hb) concentration (SpHb) by rainbow pulse CO-oximetry technology to the invasive blood Hb concentration measured by an automated clinical analyzer (Hb-Lab). METHODS: We measured the SpHb and Hb-Lab in 109 patients aged 1-5 years. Regression analysis was used to evaluate differences between the two methods. The bias, accuracy, precision, and limits of agreement of SpHb compared with Hb-Lab were calculated using the Bland-Altman method. RESULTS: Of the 109 enrolled subjects, 102 pairs of the SpHb and Hb-Lab datasets were collected. The average value of measured Hb was 12.9 ± 1.03 (standard deviation [SD]) g/dL for Hb-Lab. A significant correlation was observed between SpHb and Hb-Lab measurements (SpHb = 7.002 + 0.4722 Hb-Lab, correlation coefficient r = 0.548, 95% confidence interval = 0.329-0.615). Bland-Altman analysis showed good visual agreement, with a mean bias between SpHb and Hb-Lab of 0.188 ± 0.919 g/dL (mean ± SD). CONCLUSIONS: We concluded that non-invasive Hb measurement is useful for Hb estimation in children and provides new insights as a screening tool for anemia. IMPACT: Our results indicated a good correlation between non-invasive transcutaneous spectrophotometric estimation of arterial hemoglobin (Hb) concentration using a finger probe sensor by rainbow pulse CO-oximetry technology and invasive blood Hb concentration. Although previous studies have indicated that in patients with a worse condition, the bias between the two methods was large, this study, which was conducted on children with stable disease, showed a relatively small bias. Further studies using this non-invasive device might help to understand the current status of anemia in Japan and promote iron intake and nutritional management in children.

Growth Trajectories during the First 6 Years in Survivors Born at Less Than 25 Weeks of Gestation Compared with Those between 25 and 29 Weeks.

We aimed to determine the differences in the growth trajectories of the youngest gestational survivors (<25 weeks' gestation) up to 6 years of age compared to those of older gestational ages. Preterm infants were divided into two groups: 22−24 weeks' gestation (male (M) 16, female (F) 28) and 25−29 weeks' gestation (M 84, F 59). Z-scores of body weight (BW), body length (BL), and body mass index (BMI) were derived from Japanese standards at 1, 1.5, 3, and 6 years of corrected age. Comparisons between the two groups by sex were made using the Wilcoxon test and linear regression analysis to examine the longitudinal and time-point associations of anthropometric z-scores, the presence of small for gestational age (SGA), and the two gestational groups. BW, BL, BMI, and z-scores were significantly lower in the 22−24 weeks group at almost all assessment points. However, there were no significant differences in BW, BL, BMI, and z-scores between the two female groups after 3 years. BMI z-scores were significantly associated with the youngest gestational age and the presence of SGA at all ages in males, but not in females. The youngest gestational age had a greater influence in males on the z-score of anthropometric parameters up to 6 years of age.

Resistin in Urine and Breast Milk: Relation to Type of Feeding and Anthropometry at 1-Month.

Breast milk contains adipokines such as resistin and leptin and is known for its protective effect against obesity and insulin resistance. This pilot study aims to evaluate the correlation between resistin levels, feeding types (breast milk and formula), and anthropometric parameters in healthy 1-month-old term infants. Urine and breast milk samples were collected from 32 infants and their mothers at 1 month postpartum. Twelve infants were included in the breastfed group, while thirteen infants comprised the breastfed-dominant mix-fed group, and seven infants the formula-dominant mix-fed group. Using ELISA kits, we analyzed resistin levels in the infants' urine and the mothers' breast milk, and leptin levels in breast milk. Urinary resistin levels among the three groups were not significantly different. There was no correlation between the following: urinary resistin levels in the breastfed group with resistin levels in breast milk; resistin levels in urine with infant's body weight and weight gain; resistin levels in breast milk with weight, age, and BMI of mothers and leptin levels in breast milk. This study suggests that the type of feeding does not affect resistin levels in term infants and resistin level does not affect growth in early infancy.