RESUMEN
Maternal vitamin deficiencies are associated with low birth weight and increased perinatal morbidity and mortality. We hypothesize that maternal folate and/or vitamin B(12) restrictions alter body composition and fat metabolism in the offspring. Female weaning Wistar rats received ad libitum for 12 weeks a control diet (American Institute of Nutrition-76A) or the same with restriction of folate, vitamin B(12) or both (dual deficient) and, after confirming vitamin deficiency, were mated with control males. The pregnant/lactating mothers and their offspring received their respective diets throughout. Biochemical and body composition parameters were determined in mothers before mating and in offspring at 3, 6, 9 and 12 months of age. Vitamin restriction increased body weight and fat and altered lipid profile in female Wistar rats, albeit differences were significant with only B(12) restriction. Offspring born to vitamin-B(12)-restricted dams had lower birth weight, while offspring of all vitamin-restricted dams weighed higher at/from weaning. They had higher body fat (specially visceral fat) from 3 months and were dyslipidemic at 12 months, when they had high circulating and adipose tissue levels of tumor necrosis factor α, leptin and interleukin 6 and low levels of adiponectin and interleukin 1ß. Vitamin-restricted offspring had higher activities of hepatic fatty acid synthase and acetyl-CoA-carboxylase and higher plasma cortisol levels. In conclusion, maternal and peri-/postnatal folate and/or vitamin B(12) restriction increased visceral adiposity (due to increased corticosteroid stress), altered lipid metabolism in rat offspring perhaps by modulating adipocyte function and may thus predispose them to high morbidity later.
Asunto(s)
Composición Corporal/efectos de los fármacos , Ácido Fólico/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Vitamina B 12/farmacología , Tejido Adiposo/efectos de los fármacos , Animales , Animales Recién Nacidos , Peso al Nacer , Femenino , Masculino , Embarazo , Ratas , Ratas Wistar , Deficiencia de Vitamina B 12/metabolismoRESUMEN
Growth in utero is largely a reflection of nutrient and oxygen supply to the foetus. We studied the effects of Mn restriction per se, maternal Mn restriction, and postnatal high-fat feeding in modulating body composition, lipid metabolism and adipocyte function in Wistar/NIN (WNIN) rat offspring. Female weanling, WNIN rats received ad libitum for 4 months, a control or Mn-restricted diet and were mated with control males. Some restricted mothers were rehabilitated with control diet from conception (MnRC) or parturition (MnRP), and their offspring were raised on control diet. Some restricted offspring were weaned onto control diet (MnRW), while others continued on restricted diet throughout (MnR). A set of offspring from each group was fed high-fat diet from 9 months onwards. Body composition, adipocytes function, and lipid metabolism were monitored in male rat offspring at regular intervals. Maternal manganese restriction increased the susceptibility of the offspring to high-fat-induced adiposity, dyslipidaemia, and a proinflammatory state but did not affect their glycemic or insulin status.
Asunto(s)
Adipocitos/metabolismo , Grasas de la Dieta/efectos adversos , Dislipidemias/etiología , Manganeso/deficiencia , Fenómenos Fisiologicos Nutricionales Maternos , Obesidad/etiología , Adiposidad , Animales , Susceptibilidad a Enfermedades , Dislipidemias/inmunología , Dislipidemias/metabolismo , Dislipidemias/patología , Femenino , Resistencia a la Insulina , Lactancia , Metabolismo de los Lípidos , Lípidos/sangre , Hígado/metabolismo , Hígado/patología , Masculino , Manganeso/administración & dosificación , Obesidad/inmunología , Obesidad/metabolismo , Obesidad/patología , Embarazo , Ratas , Ratas Mutantes , Ratas WistarRESUMEN
Intrauterine growth retardation programs the fetus to manipulated metabolic changes that lead to adult diseases. Considering that chromium (Cr) supplements influence lean body mass (LBM) in both humans and experimental animals, we have studied the effect of maternal Cr restriction on muscle development and function in the rat offspring. Female weanling Wistar/NIN rats received, for 12 weeks, a control or 65% Cr-restricted diet ad libitum and mated with control males. While control mothers/offspring received control diet throughout (CrC), some restricted mothers were switched to control diet from conception (CrRC) and parturition (CrRP) and their offspring were weaned on to control diet. Half of the remaining restricted pups were weaned on to control diet (CrRW) and the other half continued on restricted diet throughout (CrR). Maternal CrR significantly decreased the percent of LBM (LBM %) and fat-free mass (FFM %) in the offspring and this was associated with decreased expression of the myogenic genes: MyoD, Myf5 and MyoG. Surprisingly, expression of the muscle atrophy genes, Atrogin and MuRF 1, was also decreased in CrR offspring. Although basal glucose uptake by muscle was higher in CrR than in CrC offspring, the stimulation with insulin was comparable, implying no change in its insulin sensitivity. Rehabilitation partly corrected myogenic and atrophic gene expression but had no effect on LBM % or FFM % or glucose uptake by muscle. The results show that maternal Cr restriction in rats may irreversibly impair muscle development and glucose uptake by muscle. Modulation of muscle atrophy appears to be an adaptive mechanism to preserve muscle mass in CrR offspring.
Asunto(s)
Alimentación Animal , Cromo/metabolismo , Músculos/embriología , Músculos/fisiología , 3-O-Metilglucosa/metabolismo , Animales , Composición Corporal , Índice de Masa Corporal , Femenino , Regulación de la Expresión Génica , Glucosa/metabolismo , Resistencia a la Insulina/fisiología , Masculino , Exposición Materna , Atrofia Muscular/patología , Ratas , Ratas WistarRESUMEN
OBJECTIVE: We demonstrated previously that chronic maternal micronutrient restriction altered the body composition in rat offspring and may predispose offspring to adult-onset diseases. Chromium (Cr) regulates glucose and fat metabolism. The objective of this study is to determine the long-term effects of maternal Cr restriction on adipose tissue development and function in a rat model. RESEARCH DESIGN AND METHODS: Female weanling WNIN rats received, ad libitum, a control diet or the same with 65% restriction of Cr (CrR) for 3 months and mated with control males. Some pregnant CrR mothers were rehabilitated from conception or parturition and their pups weaned to control diet. Whereas some CrR offspring were weaned to control diet, others continued on CrR diet. Various parameters were monitored in the offspring at three monthly intervals up to 15-18 months of age. RESULTS: Maternal Cr restriction significantly increased body weight and fat percentage, especially the central adiposity in both male and female offspring. Further, the expression of leptin and 11 beta-hydroxysteroid dehydrogenase 1 genes were significantly increased in CrR offspring of both the sexes. Adipocytokine levels were altered in plasma and adipose tissue; circulating triglyceride and FFA levels were increased, albeit in female offspring only. Rehabilitation regimes did not correct body adiposity but restored the circulating levels of lipids and adipocytokines. CONCLUSIONS: Chronic maternal Cr restriction increased body adiposity probably due to increased stress and altered lipid metabolism in WNIN rat offspring, which may predispose them to obesity and associated diseases in later life.
Asunto(s)
Tejido Adiposo/fisiología , Cromo/deficiencia , Privación Materna , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Adiponectina/genética , Tejido Adiposo/anatomía & histología , Tejido Adiposo/efectos de los fármacos , Animales , Peso Corporal , Cromo/sangre , Modelos Animales de Enfermedad , Femenino , Leptina/genética , Lípidos/fisiología , Masculino , PPAR gamma/genética , Embarazo , ARN Ribosómico 18S/genética , Ratas , Ratas Endogámicas , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Maternal undernutrition increases the risk of adult chronic diseases, such as obesity and type 2 diabetes. This study evaluated the effect of maternal zinc restriction in predisposing the offspring to adiposity and altered insulin response in later life. Seventy-day-old female Wistar/NIN rats received a control (ZnC) or zinc-restricted (ZnR) diet for 2 weeks. Following mating with control males, a subgroup of the ZnR dams were rehabilitated with ZnC diet from parturition. Half the offspring born to the remaining ZnR dams were weaned onto the ZnC diet and the other half continued on the ZnR diet throughout their life. Body composition, glucose tolerance, insulin response and plasma lipid profile were assessed in male and female offspring at 3 and 6 months of age. The ZnR offspring weighed less than control offspring at birth and weaning and continued so until 6 months of age. Rehabilitation regimens corrected the body weights of male but not female offspring. Maternal zinc restriction increased the percentage of body fat and decreased lean mass, fat-free mass and fasting plasma insulin levels in both male and female offspring at 6 months of age. Also, glucose-induced insulin secretion was decreased in female but not male offspring. Despite the differences in fasting insulin and the area under the curve for insulin, the fasting glucose and the area under the curve for glucose were in general comparable among offspring of different groups. Rehabilitation from parturition or weaning partly corrected the changes in the percentage of body fat but had no such effect on other parameters. Changes in plasma lipid profile were inconsistent among the offspring of different groups. Thus chronic maternal zinc restriction altered the body composition and impaired the glucose-induced insulin secretion in the offspring.
Asunto(s)
Desnutrición/complicaciones , Desnutrición/fisiopatología , Fenómenos Fisiologicos Nutricionales Maternos , Intercambio Materno-Fetal/fisiología , Complicaciones del Embarazo/fisiopatología , Zinc/deficiencia , Animales , Animales Recién Nacidos , Glucemia/metabolismo , Composición Corporal , Dieta , Femenino , Prueba de Tolerancia a la Glucosa , Insulina/sangre , Insulina/metabolismo , Resistencia a la Insulina , Secreción de Insulina , Masculino , Embarazo , Ratas , Ratas Wistar , Zinc/administración & dosificaciónRESUMEN
OBJECTIVE: We investigated the long-term effects of maternal/postnatal magnesium (Mg) restriction on adiposity, glucose tolerance, and insulin secretion in the offspring and the probable biochemical mechanisms associated with them. METHODS AND PROCEDURES: Female weanling Wistar/NIN (WNIN) rats received a control diet or 70% Mg-restricted (MgR) diet for 9 weeks and mated with control males. A third of the restricted dams were shifted to control diet from parturition. Half of the pups born to the remaining restricted dams were weaned on to control diet, while the other half continued on MgR diet. Various parameters were determined in the offspring at 18 months of age. RESULTS: The percentage of body fat increased, lean body mass (LBM) and fat free mass (FFM) decreased in restricted offspring and were irreversible by rehabilitation. While glucose tolerance and insulin resistance (IR) were comparable among groups, glucose-stimulated insulin secretion and basal glucose uptake by the diaphragm were significantly decreased in restricted offspring and not corrected by rehabilitation. Plasma leptin was lower, and tumor necrosis factor-alpha (TNF-alpha) was higher in restricted offspring, whereas expression of fatty acid synthase (FAS) and fatty acyl transport protein 1 (FATP 1) was higher in liver and adipose tissue. While changes in FAS and FATP 1 were not correctible by rehabilitation, those in leptin and TNF-alpha were corrected by rehabilitation from parturition but not from weaning. Tissue oxidative stress and antioxidant status were comparable among groups. DISCUSSION: Results indicate that maternal and postnatal Mg status is important in the long-term programming of body adiposity and insulin secretion in rat offspring.
Asunto(s)
Adiposidad/fisiología , Animales Recién Nacidos/fisiología , Resistencia a la Insulina/fisiología , Deficiencia de Magnesio/fisiopatología , Magnesio/fisiología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Adipoquinas/sangre , Tejido Adiposo/metabolismo , Animales , Composición Corporal/fisiología , Ácido Graso Sintasas/metabolismo , Proteínas de Unión a Ácidos Grasos/metabolismo , Femenino , Glucosa/metabolismo , Insulina/metabolismo , Lípidos/sangre , Hígado/metabolismo , Embarazo , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
According to the fetal programming hypothesis, impaired intrauterine development results in insulin resistance and associated metabolic disturbances. Recently, we reported increased body fat, a forerunner of insulin resistance, in the pups of mineral-restricted rat dams. To identify the causative mineral(s), the effect of magnesium restriction was assessed. Female weanling WNIN rats (n = 21) consumed ad libitum for 9 wk a 70% magnesium-restricted diet or were pair-fed a control (C) diet (n = 7). After 9 wk, they were mated with control males. Control dams and pups were fed the control diet throughout, whereas 7 Mg-restricted dams were switched to the control diet at parturition and their pups weaned onto the control diet (RP). Pups of the remaining 14 restricted dams were weaned onto the control diet (RW) or the Mg-restricted diet (R). All groups had 8 male pups from weaning. Pups were studied on postnatal d 90 and 180. R pups weighed less than C pups at weaning, but both RP and RW pups caught up with controls by d 90. At this time, R pups were neither insulin resistant nor glucose intolerant, but had a higher percentage of body fat and plasma triglycerides and lower lean body and fat-free mass than C pups. These variables were partially corrected in both RP and RW pups. On postnatal d 180, R, RP, and RW pups were insulin resistant and had a lower insulin response to a glucose challenge than C pups; however, glucose tolerance was impaired only in RW pups. Thus, maternal magnesium restriction irreversibly increases body fat and induces insulin resistance in pups by 6 mo of age, whereas additional perinatal Mg deficiency impairs glucose tolerance.
Asunto(s)
Intolerancia a la Glucosa/etiología , Resistencia a la Insulina , Deficiencia de Magnesio/complicaciones , Deficiencia de Magnesio/fisiopatología , Complicaciones del Embarazo , Efectos Tardíos de la Exposición Prenatal , Animales , Animales Recién Nacidos , Composición Corporal , Femenino , Feto/metabolismo , Homeostasis , Lípidos/sangre , Magnesio/sangre , Masculino , Embarazo , Ratas , Ratas EndogámicasRESUMEN
BACKGROUND: Maternal undernutrition is hypothesized to predispose the offspring to disease in adult life. The relevance of maternal macronutrient deficiency has been well studied but not that of micronutrients. OBJECTIVE: To assess the effect of maternal dietary mineral restriction per se on oral glucose tolerance (OGT), insulin resistance (IR) and fat metabolism in offspring. DESIGN: Female weanling Wistar/NIN rats received a control or a 50% mineral-restricted (MR) diet for 12 weeks, by which time MR rats had lower plasma Fe, Zn, Mg and Ca concentrations. Following mating with control males, a third of the MR dams were shifted to the control diet from parturition. Half of the pups born to the remaining MR dams were weaned onto the control diet while the other half continued on the MR diet. RESULTS: Pregnant MR dams had a higher abortion rate, body weights of their pups at birth and weaning were lower and rehabilitation had no beneficial effect. No offspring had impaired OGT, and IR status was comparable among different groups on postnatal days 40, 70, 100 or 180. Compared with controls, total body electrical conductivity measurements indicated significantly higher body fat %, lower lean body mass and fat-free mass in MR offspring besides elevated plasma triacylglycerols. Mineral rehabilitation from parturition or weaning had little effect on these changes, which did not appear to be due to increased oxidative stress. CONCLUSIONS: Maternal MR per se resulted in an increase in body fat and in plasma triacylglycerol concentrations in the offspring. These changes had, however, no discernable effect on insulin sensitivity over the first 180 days of life.