Na+-K+-ATPase alpha 2-gene and skeletal muscle characteristics in response to long-term overfeeding.
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The role of Na(+)-K(+)-ATPase alpha2-gene BglII polymorphism in the changes of skeletal muscle metabolic properties after a 100-day overfeeding protocol conducted with 12 pairs of monozygotic twins is reported. The activities of oxoglutarate dehydrogenase (OGDH) and phosphofructokinase (PFK) were determined from muscle biopsies. A larger increase in the total fat mass (127 vs. 61%) (P < 0.05) and low-density lipoprotein cholesterol (20 vs. 0.7%) (P = 0.05) in 8.0/8.0-kb [3.3-kb negative (-); n = 7 pairs] than in 8.0/3.3 + 3.3/3.3-kb [3.3-kb positive (+); n = 5 pairs] subjects was observed. OGDH activity decreased in 3.3-kb(-) (-15%), whereas PFK (+26%) as well as the PFK-to-OGDH ratio (90%) increased. In contrast, among 3.3-kb(+), OGDH increased (+54%) together with a decrease in PFK (-1%) and PFK-to-OGDH ratio (-5%). These changes were significantly different between genotypes (P from <0.05 to 0.01). In conclusion, fat mass, low-density lipoprotein cholesterol, and skeletal muscle glycolytic-to-oxidative enzyme ratio increased more in the alpha2-gene 3.3-kb(-) subjects with overfeeding, suggesting more unfavorable metabolic changes compared with the 3.3-kb(+) subjects. (+info)
The effects of ad libitum overfeeding and moderate and marked dietary restriction on age-related spontaneous pituitary gland pathology in Sprague-Dawley rats.
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This study compared the effects of ad libitum (AL) overfeeding and moderate or marked dietary restriction (DR) on the pathogenesis of aged-related pituitary gland changes in Sprague-Dawley (SD) rats. SD rats were fed Purina Certified Rodent Diet AL (group 1), DR at 72-79% of AL (group 2), DR at 68-72% of AL (group 3) or DR at 47-48% of AL (group 4) for 106 weeks. Interim necropsies were performed at 13, 26, and 53 weeks, after a 7-day 5-bromo-2-deoxyuridine (BrdU)-filled minipump implantation. Body weights, organ weights and insulin-like growth factor 1 (IGF-1) serum levels were measured at interim and final necropsies. Serum levels of prolactin (PRL), progesterone, estradiol, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured at 53 and/or 106 weeks. In addition to the routine histopathologic examination, determination of 7 stereologic parameters after pituitary immunohistochemistry of PRL, growth hormone (GH) and BrdU was done in both sexes at 13, 26, and 53 weeks. Body and pituitary weights were proportional to the food intake. In AL-fed rats, hyperplastic and neoplastic changes developed early and progressed with age, affecting almost all animals by 106 weeks. These changes were associated with high PRL serum levels. Pituitary adenomas were the most common cause of death in both sexes. In DR rats, a delayed onset and a decreased incidence of pituitary tumors were observed in association with decreased serum IGF-1, PRL, estradiol, and LH levels. The results of the stereological analysis demonstrated that, compared to AL-fed rats, pituitary glands from DR rats contained lower PRL and GH secreting cell volumes, and a lower epithelial cell BrdU labeling index, which correlated with a lower incidence of pituitary tumors at study termination. Moderate and marked degrees of DR delayed the onset of pituitary tumors in a temporal- and dose-related manner. In contrast to marked DR, which dramatically reduced the incidence of hyperplastic and neoplastic pituitary gland changes, moderate DR delayed the onset but did not prevent the development of pituitary tumors. (+info)
Influence of progesterone supplementation during the first third of pregnancy on fetal and placental growth in overnourished adolescent ewes.
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Overnourishing adolescent ewes throughout pregnancy promotes maternal tissue synthesis at the expense of placental growth, which in turn leads to a major decrease in lamb birth weight. As maternal dietary intakes are inversely related to peripheral progesterone concentrations in these adolescent dams, it was hypothesized that sup-optimal progesterone concentrations in overnourished dams may compromise the growth of the differentiating conceptus resulting in fewer uterine caruncles being occupied and, hence, fewer placentomes formed. This hypothesis was tested by supplementing overnourished adolescent dams with exogenous progesterone during early pregnancy and determining the impact on pregnancy outcome at term. Embryos recovered from superovulated adult ewes inseminated by a single sire were transferred in singleton to the uterus of peripubertal adolescent recipients. After transfer of embryos, ewes were offered a moderate or high amount of a complete diet (n=11 per group). A further high intake group received a progesterone supplement each day from day 5 to day 55 of gestation (term=145 days) to restore circulating progesterone concentrations to moderate values throughout the first third of pregnancy (n=11). For ewes establishing pregnancies (n=7 per group), live weight gain during the first 100 days of gestation was 66+/-4, 323+/-17 and 300+/-7 g per day, body condition score at term was 2.1+/-0.05, 3.0+/-0.08 and 3.1+/-0.07 units and the duration of gestation after spontaneous delivery was 148+/-1.7, 144+/-0.8 and 143+/-0.8 days for the moderate intake, high intake and high intake plus progesterone groups, respectively. At delivery, fetal cotyledon mass (136+/-12.1 versus 57+/-8.2g, P<0.001) and lamb birth weight (5164+/-151 versus 2893+/-381 g, P<0.001) were higher in moderate intake than in high intake dams. Progesterone supplementation restored circulating concentrations to moderate values during the first third of gestation. Lamb birth weight in the high intake plus progesterone group (4150+/-389 g) was intermediate between the high intake (P<0.02) and moderate intake (P<0.05) groups, but this change in birth weight was not associated with corresponding changes in fetal cotyledon mass (76+/-10.3 g). Moreover, the number of fetal cotyledons was similar in all three groups. Thus, progesterone did not directly affect the growth of the fetal cotyledon but may have influenced placental vascularity, blood flow or nutrient transfer capacity or alternatively the development of the embryonic inner cell mass. (+info)
Dual forms of malnutrition in the same households in Malaysia--a case study among Malay rural households.
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This report is a part of a multi-centre study in Asia on the problem of dual forms of malnutrition in the same households. In Malaysia, the prevalence of underweight and stunting persist among young children from poor rural areas. Overweight in adults, especially women from poor rural areas has been reported in recent years. Thus, this study was undertaken in order to assess the presence of the dual burden of underweight child-overweight mother pairs in a poor rural community. Out of 140 Malay households identified to have at least one child aged 1-6 years and mother aged above 20 years, 52.1% of the mothers were overweight, 15.7% of the children were underweight, 27.1% stunted and 5% wasted. Socio-economic background and food intake frequency data were collected from 54 underweight child/overweight mother pairs (UW/OW) and 41 normal weight child/normal weight mother pairs (NW/NW). Compared with the overweight mothers, a higher percentage of the normal weight mothers had received secondary education, were employed and with a higher household monthly income, although these differences were not significant. Patterns of food intake of the mothers and children appeared to have more similarities than differences between the UW/OW and NW/NW groups. Quantitative dietary intakes for 2 days using 24-hr recall and physical activity energy expenditure over the same period were assessed in a sub-group of UW/OW and NW/NW mothers and children. The NW/NW children showed significantly higher intake of total calories, fat and riboflavin than the UW/OW counterparts. Mean energy and nutrient intake of mothers from both groups were not significantly different, although the NW/NW mothers showed higher intake adequacy for total calories and most nutrients. While most of the mothers from both groups reported having no chronic illnesses, about half of the children in both groups had infections, especially gastrointestinal infections, over a 2-week period. Energy expenditure from physical activity for both UW/OW and NW/NW mothers and children did not differ significantly. This study confirmed inadequate intake of total energy and nutrients as the major factor for underweight in Malay children from rural areas. However, assessing intake and physical activity by interview methods were not sensitive enough to overcome perceived problems of under-reporting of energy intake and over-estimation of energy expenditure, especially by overweight subjects. Further investigations on a larger sample are necessary to understand the family dynamics leading to the double burden of malnutrition within the same household. (+info)
A case study on dual forms of malnutrition among selected households in District 1, Tondo, Manila.
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The co-existence of under-and overnutrition in developing countries might be the resultant factor of a marked shift in dietary and lifestyle practices of people, especially in urban areas. The eating of high fat, high caloric diets, the presence of inactive entertainment devices and mechanized labour influence patterns of food demand and physical activity. This study identified factors associated with the occurrence of under/overweight or normal/normal nutritional status of child-mother pairs in one household. This study was conducted in two phases. The first phase was a survey of 376 child-mother pairs. The children aged 33-83 months were attending classes in government day care centres. Anthropometric indices: weight-for-age Z score (WAZ) < or = -2SD was used to classify underweight in children. WAZ+1 to -1SD was used to indicate normal nutritional status in children, specifically for this study, in order to establish a more homogenous group. Body mass index (BMI) > or = 25 kg/m2 was used to measure overweight among mothers. Results showed that about 59% of the child-mother pairs were suffering from two different types of malnutrition. From this, 31 (8.2%) child-mother pairs in the same household were experiencing underweight/overweight: the child was underweight and the mother was overweight. The second phase of the study was an in-depth study of these 31 under/overweight child-mother pairs and 30 randomly selected normal/normal pairs. Pre-tested questionnaires were used to gather socio-economic-demographic data; 3 day 24-h food recall for dietary intake and 24-h activity recall for physical activity. Results showed that the different factors associated with the existence of underweight child/overweight mother (UC/OM) or normal child/normal mother (NC/NM) in this study were: mother's educational level, mother's occupation, and number of children in the household; energy intake, the preference of meats, sweets and sugars among children or meats and fried foods among mothers; and mother's perception on body size. Physical activity of both mothers and children was higher in the UC/OM than in the NC/NM group. The problem of undernutrition and overnutrition in one household poses enormous challenges. Although this study cannot make an inference to the whole population, the results indicate that there is a need to consider whether public health programs should focus on healthy diet and lifestyle patterns that will lead to optimal health outcomes at both ends of the spectrum of nutritional status. (+info)
Maternal growth hormone treatment from day 35 to 80 of gestation alters nutrient partitioning in favor of uteroplacental growth in the overnourished adolescent sheep.
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Overnourishing the pregnant adolescent ewe promotes maternal tissue synthesis at the expense of placental growth and leads to a major reduction in lamb birth weight at term. Growth hormone (GH) secretion is attenuated in these overnourished dams and the maternal somatotrophic axis may play a key role in coordinating nutrient usage in the pregnant adolescent. Thus we investigated whether increasing maternal GH during the period of rapid placental proliferation alters nutrient partitioning between the maternal, placental, and fetal tissues as assessed at Day 81 of gestation. Adolescent recipient ewes were implanted with singleton embryos, derived from superovulated dams and a single sire on Day 4 postestrus. Thereafter, the ewes were offered either a high (H) or moderate intake (M) of the same complete diet. From Day 35 to 80 of gestation, ewes were either injected twice daily (s.c. at 0800 and 1800 h) with recombinant bovine GH (bGH, 0.14 mg/kg live weight/day) or remained untreated (n = 8 ewes per group). Maternal concentrations of GH, insulin, insulin-like growth factor (IGF-1), glucose, and non-esterified fatty acids (NEFAs) were higher, and leptin secretion lower, in bGH-treated dams from both nutritional groups. Maternal body weight gain was higher in H versus M groups and was independent of bGH treatment. Treatment with bGH reduced relative perirenal and carcass fat deposition and increased carcass protein content in both H and M dams. Uteroplacental mass (uterus + placentomes + fetal membranes) averaged 1099, 1069, 1112, and 1754 g in M, H, M+GH, and H+GH groups. This significant increase in uteroplacental development in the H+GH group was associated with higher fetal kidney and liver weights and elevated fetal insulin, glucose, and lactate concentrations. Treatment with bGH also induced polyhydramnios in the H group. The transplacental glucose gradient was increased twofold in the H+GH group but placental GLUT- 1 and GLUT-3 expression was unaffected. In conclusion, administration of GH during the period of rapid placental proliferation alters endocrine status and thus nutrient partitioning in the overnourished adolescent dam in favor of uteroplacental and fetal growth. It remains to be established whether these effects are due wholly to alterations in maternal metabolism or if they also reflect an effect of bGH and/or the IGF system at the level of the uteroplacenta. (+info)
Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited.
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Type 2 diabetes is a worldwide increasing disease resulting from the interaction between a subject's genetic makeup and lifestyle. In genetically predisposed subjects, the combination of excess caloric intake and reduced physical activity induces a state of insulin resistance. When beta cells are no longer able to compensate for insulin resistance by adequately increasing insulin production, impaired glucose tolerance appears, characterized by excessive postprandial hyperglycemia. Impaired glucose tolerance may evolve into overt diabetes. These 3 conditions, ie, insulin resistance, impaired glucose tolerance, and overt diabetes, are associated with an increased risk of cardiovascular disease. Because all these conditions are also accompanied by the presence of an oxidative stress, this article proposes oxidative stress as the pathogenic mechanism linking insulin resistance with dysfunction of both beta cells and endothelium, eventually leading to overt diabetes and cardiovascular disease. This hypothesis, moreover, may also contribute to explaining why treating cardiovascular risk with drugs, such as calcium channel blockers, ACE inhibitors, AT-1 receptor antagonists, and statins, all compounds showing intracellular preventive antioxidant activity, results in the onset of new cases of diabetes possibly being reduced. (+info)
Nutritionally mediated placental growth restriction in the growing adolescent: consequences for the fetus.
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Human adolescent pregnancy is characterized by poor pregnancy outcome; the risks of spontaneous miscarriage, prematurity, and low birth weight are particularly acute in girls who are still growing at the time of conception. Studies using a highly controlled sheep paradigm demonstrate that, in growing adolescents who are overnourished throughout pregnancy, growth of the placenta is impaired, resulting in a decrease in lamb birth weight relative to control-fed adolescents of equivalent age. Rapid maternal growth is also associated with increased spontaneous abortion rates in late gestation and a reduction in gestation length. Nutritionally sensitive hormones of the maternal somatotrophic axis may orchestrate nutrient partitioning in this paradigm and the particular role of growth hormone is discussed. At midgestation, the placentae of rapidly growing dams exhibit less proliferation in the fetal trophectoderm and reduced placental mRNA expression of a range of angiogenic factors. These changes occur before differences in placental size are apparent but may impact on subsequent vascularity. By late pregnancy, placental mass in the rapidly growing versus the control dams is reduced by approximately 45%; the fetuses display asymmetric growth restriction and are hypoxic and hypoglycemic. These growth-restricted pregnancies are associated with major reductions in absolute uterine and umbilical blood flows, leading to attenuated fetal oxygen, glucose, and amino acid uptakes. Placental glucose transport capacity is markedly reduced in the rapidly growing dams but is normal when expressed on a weight-specific placental basis. Thus, it is the small size of the placenta per se rather than alterations in its nutrient metabolism or transfer capacity that is the major limitation to fetal growth in the growing adolescent sheep. Information obtained from this highly controlled paradigm is clearly relevant to the clinical management of human adolescent pregnancies. In addition, the paradigm provides a robust model of placental growth restriction that replicates many of the key features of human intrauterine growth restriction per se. (+info)