Fetal overgrowth and weight trajectories during infancy and adiposity in early childhood.

BACKGROUND: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood. Little is known about how infancy growth trajectories affect adiposity in early childhood in LGA. METHODS: In the Shanghai Birth Cohort, we followed up 259 LGA (birth weight >90th percentile) and 1673 appropriate-for-gestational age (AGA, 10th-90th percentiles) children on body composition (by InBody 770) at age 4 years. Adiposity outcomes include body fat mass (BFM), percent body fat (PBF), body mass index (BMI), overweight/obesity, and high adiposity (PBF >85th percentile). RESULTS: Three weight growth trajectories (low, mid, and high) during infancy (0-2 years) were identified in AGA and LGA subjects separately. BFM, PBF and BMI were progressively higher from low- to mid-to high-growth trajectories in both AGA and LGA children. Compared to the mid-growth trajectory, the high-growth trajectory was associated with greater increases in BFM and the odds of overweight/obesity or high adiposity in LGA than in AGA children (tests for interactions, all P < 0.05). CONCLUSIONS: Weight trajectories during infancy affect adiposity in early childhood regardless of LGA or not. The study is the first to demonstrate that high-growth weight trajectory during infancy has a greater impact on adiposity in early childhood in LGA than in AGA subjects. IMPACT: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood, but little is known about how weight trajectories during infancy affect adiposity during early childhood in LGA subjects. The study is the first to demonstrate a greater impact of high-growth weight trajectory during infancy (0-2 years) on adiposity in early childhood (at age 4 years) in subjects with fetal overgrowth (LGA) than in those with normal birth size (appropriate-for-gestational age). Weight trajectory monitoring may be a valuable tool in identifying high-risk LGA children for close follow-ups and interventions to decrease the risk of obesity.

Prenatal and early postnatal exposure to high-saturated-fat diet represses Wnt signaling and myogenic genes in offspring rats.

The prenatal and early postnatal period is a key developmental window for nutrition status, and high-fat exposure in this period has been shown to be associated with type 2 diabetes, obesity and other features of metabolic disorders later in life. The present study was designed to investigate the underlying molecular mechanisms and role of relative genes involved in this process. We investigated the impact of prenatal and early postnatal exposure to a high-saturated-fat diet on the regulation of the Wnt signaling pathway and myogenic genes in skeletal muscle of rat offspring as well as the serum and muscle physiological outcomes. Timed-pregnant Sprague-Dawley rats were fed either a control (C, 16% kcal fat) or high-saturated-fat diet (HF, 45% kcal fat) throughout gestation and lactation. After weaning, female offspring were fed a control diet to generate two offspring groups: control diet-fed offspring of control diet-fed dams (C/C) and control diet-fed offspring of HF diet-fed dams (HF/C). The serum glucose of the HF/C offspring (5.58 ± 0.26 mmol/L) was significantly higher than that of C/C offspring (4.97 ± 0.28 mmol/L), and the Homeostasis Model Assessment-Insulin Resistance of HF/C offspring (2.00 ± 0.11) was also significantly higher when compared with C/C (1.84 ± 0.09). Furthermore, HF/C offspring presented excessive intramuscular fat accumulation (1.8-fold, P < 0.05) and decreased muscle glycogen (1.3-fold, P < 0.05), as well as impairment of muscle development at the age of 12 weeks. Meanwhile, we observed the repression of Wnt/ß-catenin signaling and myogenic genes in HF/C offspring. The present study indicates that prenatal and early postnatal exposure to a high-saturated-fat diet suppresses the development of skeletal muscle and myogenic genes via Wnt/ß-catenin signaling, and the inappropriate muscle development could potentially contribute to the predisposition of offspring to develop metabolic-syndrome-like phenotype in adulthood.

Vitamin E regulates adipocytokine expression in a rat model of dietary-induced obesity.

The aim of this study was to determine the effect of the antioxidant vitamin E (VE) on adiponectin and leptin expression in obese rats. Thirty weaning male Sprague-Dawley rats were divided into three groups as follows: (1) a control group, fed with normal chow; (2) a diet-induced obesity group (DIO), fed with a high-fat diet and (3) an intervention group, fed with a high-fat diet supplemented with VE (350 mg/kg). After 10 weeks of being fed according to these group assignments, rats were weighed and euthanized. Blood and adipose tissues were then immediately collected; mRNA and protein levels of leptin and adiponectin were measured by realtime reverse transcription-polymerase chain reaction and Western blotting. Biomarkers of oxidative stress, including serum levels of 8-epi-prostaglandin-F(2)alpha (8-epi-PGF(2)alpha) and glutathione peroxidase activity, were also examined. Adiponectin and leptin levels were lower in the DIO group than in the control group. VE intervention increased the expression of both leptin and adiponectin (P values < 0.05). Association analysis showed that serum leptin levels correlated positively with body fat mass (r = 0.601, P < 0.05). Both serum leptin and adiponectin levels were associated with the presence of serum 8-epi-PGF2 alpha (leptin, r = 0.513, P < 0.05; adiponectin, r = -0.422, P < 0.05). Administration of VE decreases leptin and adiponectin expression in obese rats. This finding is consistent with the view that antioxidants can play an important role in the treatment of obesity-related diseases.

Effects of dietary supplementation with vitamin E and selenium on rat hepatic stellate cell apoptosis.

AIM: To evaluate the effects of dietary supplementation with vitamin E and selenium on proliferation and apoptosis of hepatic stellate cells (HSCs), in acute liver injury induced by CCl(4), and to explore their role in the recovery from hepatic fibrosis phase. METHODS: An acute liver damage model of rats was established by intraperitoneal injection of carbon tetrachloride (0.3 mL/100 g body weight) twice a week, then the rats were killed at 6, 24, 48, and 72 h after the first and third injection, respectively. A liver fibrosis model was established by the same injection for 8 wk. Then three rats were killed at 3, 7, 14, and 28 d after the last injection, respectively. The rats from the intervention group were fed with chow supplemented with vitamin E (250 mg/kg) and selenium (0.2 mg/kg), and the rats in the normal control group and pathological group were given standard chow. Livers were harvested and stained with hematoxylin and eosin, Sirius red. Activated HSCs were determined by alpha-smooth muscle actin immunohistochemistry staining. Apoptotic HSCs were determined by dual staining with the terminal deoxynucleotidyl transferase UTP nick end labeling (TUNEL) and alpha-smooth muscle actin immunohistochemistry. Serum alanine aminotransferase and aspartate aminotransferase were also analyzed. RESULTS: In the acute liver damage model, the degree of liver injury was more serious in the pathological group than in the intervention group. At each time point, the number of activated HSCs was less in the intervention group than in the pathological group, while the number of apoptotic HSCs was more in the intervention group than in the pathological group. In the liver fibrosis model, the degree of liver fibrosis was more serious in the pathological group than in the intervention group. At each time point, the number of activated HSCs was less in the intervention group than in the pathological group, and the number of apoptotic HSCs was more in the intervention group than in the pathological group. CONCLUSION: Vitamin E and selenium supplementation at the given level can inhibit CCl(4)-induced activation and proliferation of HSCs and promote the apoptosis of activated HSCs in acute damage phase. Vitamin E and selenium can also effectively decrease the degree of hepatic fibrosis and promote the recovery process.

[Effect of antioxidant on hepatic stellate cell proliferation and apoptosis during recovery from liver fibrosis].

OBJECTIVE: Effects of dietary supplementation of vitamin E and selenium on proliferation and apoptosis of activated hepatic stellate cell(HSC) were investigated in the rat model of liver fibrosis induced by intraperitoneal injection with CCl4. METHODS: Activated HSC was determined by alpha-smooth muscle actin immunohistochemistry staining and apoptotic HSC determined by dual staining both of the terminal deoxynucleotidyl transferase UTP nick end labeling(TUNEL) and of alpha-smooth muscle actin immunohistochemistry. RESULT: During fibrosis recovery, the number of activated HSCs both in pathological group and in intervention group went down gradually,meanwhile, both the number of apoptotic HSCs and the collagen liver also descend little by little. These data confirmed that HSCs had the core effect on liver fibrogenesis and apoptosis may be a major factor regulating HSCs numbers during the injury-fibrosis-recovery sequence. At each time point, the number of activated HSCs in pathological group is more than intervention group, while apoptotic HSCs are less, which suggested dietary supplement with antioxidative nutrients had effect on HSC apoptosis but more studies are necessary to make the mechanism clearer. CONCLUSION: Dietary supplement with proper vitamin E and selenium can effectively lighten the hepatic fibrosis and promote the recovery of hepatocyte and the degradation of the existing collagens, ie, it is beneficial to the recovery of hepatic fibrosis.