RESUMO
We investigated whether gestational diabetes mellitus (GDM) associated with maternal obesity modifies the placental profile of F4-Neuroprostanes and F2-Isoprostanes, metabolites of non-enzymatic oxidation of docosahexaenoic acid (DHA) and arachidonic acid (AA), respectively. Twenty-five placental samples were divided into lean (n=11), obesity (n=7) and overweight/obesity+GDM (n=7) groups. F4-Neuroprostanes and F2-Isoprostanes were higher in obesity compared to lean controls, but reduced to levels similar to lean women when obesity is further complicated with GDM. Lower content of F2-Isoprostanes suggests adaptive placental responses in GDM attenuating oxidative stress. However, low levels of placental F4-Neuroprostanes may indicate impaired DHA metabolism in GDM, affecting fetal development and offspring health. These results were not related to differences in placental content of DHA, AA and polyunsaturated fatty acids status nor to maternal diet or gestational weight gain. Placental DHA and AA metabolism differs in obesity and GDM, highlighting the importance of investigating the signalling roles of F4-Neuroprostanes and F2-Isoprostanes in the human term placenta.
Assuntos
Diabetes Gestacional , Neuroprostanos , Obesidade Materna , Humanos , Feminino , Gravidez , Neuroprostanos/metabolismo , Isoprostanos , Diabetes Gestacional/metabolismo , Placenta/metabolismo , F2-Isoprostanos/metabolismo , Obesidade Materna/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Araquidônico/metabolismo , Obesidade/metabolismoRESUMO
The rise in prevalence of obesity in women of reproductive age in developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health. Placental lipid metabolism is disrupted by maternal obesity, which possibly affects the life-long health of the offspring. Here, we investigated placental lipid metabolism in women with pre-gestational obesity as a sole pregnancy complication and compared it to placental responses of lean women. Open profile and targeted lipidomics were used to assess placental lipids and oxidised products of docosahexaenoic (DHA) and arachidonic acid (AA), respectively, neuroprostanes and isoprostanes. Despite no overall signs of lipid accumulation, DHA and AA levels in placentas from obese women were, respectively, 2.2 and 2.5 times higher than those from lean women. Additionally, a 2-fold increase in DHA-derived neuroprostanes and a 1.7-fold increase in AA-derived isoprostanes were seen in the obese group. These changes correlated with a 70% decrease in placental FABP1 protein. Multivariate analyses suggested that neuroprostanes and isoprostanes are associated with maternal and placental inflammation and with birth weight. These results might shed light on the molecular mechanisms associated with altered placental fatty acid metabolism in maternal pre-gestational obesity, placing these oxidised fatty acids as novel mediators of placental function.
Assuntos
Proteínas de Ligação a Ácido Graxo/metabolismo , Isoprostanos/metabolismo , Fenômenos Fisiológicos da Nutrição Materna/genética , Neuroprostanos/metabolismo , Obesidade Materna/metabolismo , Adulto , Peso ao Nascer , Feminino , Humanos , Inflamação , Metabolismo dos Lipídeos , Placenta/metabolismo , GravidezRESUMO
Long-chain polyunsaturated fatty acids (LC-PUFA), mainly docosahexaenoic (DHA) and arachidonic acids (AA), are critical for adequate fetal growth and development. We investigated mRNA expression of proteins involved in hydrolysis, uptake and/or transport of fatty acids in placenta of fifteen full term normal pregnancies and eleven pregnancies complicated by intrauterine growth restriction (IUGR) with normal umbilical blood flows. The mRNA expression of LPL, FATPs (-1, -2 and -4) and FABPs (-1 and -3) was increased in IUGR placentas, however, tissue profile of LC-PUFA was not different between groups. Erythrocytes from both mothers and fetuses of the IUGR group showed lower concentrations of AA and DHA and inferior DHA/ALA ratio compared to normal pregnancies (P < 0.05). We hypothesize that reduced circulating levels of AA and DHA could up-regulate mRNA expression of placental fatty acids transporters, as a compensatory mechanism, however this failed to sustain normal LC-PUFA supply to the fetus in IUGR.
Assuntos
Eritrócitos/metabolismo , Proteínas de Transporte de Ácido Graxo/metabolismo , Ácidos Graxos/metabolismo , Retardo do Crescimento Fetal/metabolismo , Placenta/metabolismo , Adulto , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/genética , Feminino , Retardo do Crescimento Fetal/genética , Humanos , Lipase Lipoproteica/genética , Troca Materno-Fetal , Gravidez , RNA Mensageiro/genética , Adulto JovemRESUMO
The quality of dietary lipids in the maternal diet can programme the offspring to diseases in later life. We investigated whether the maternal intake of palm oil or interesterified fat, substitutes for trans-unsaturated fatty acids (FA), induces metabolic changes in the adult offspring. During pregnancy and lactation, C57BL/6 female mice received normolipidic diets containing partially hydrogenated vegetable fat rich in trans-unsaturated fatty acids (TG), palm oil (PG), interesterified fat (IG) or soyabean oil (CG). After weaning, male offspring from all groups received the control diet until day 110. Plasma glucose and TAG and liver FA profiles were ascertained. Liver mitochondrial function was accessed with high-resolution respirometry by measuring VO2, fluorimetry for detection of hydrogen peroxide (H2O2) production and mitochondrial Ca2+ uptake. The results showed that the IG offspring presented a 20 % increase in plasma glucose and both the IG and TG offspring presented a 2- and 1·9-fold increase in TAG, respectively, when compared with CG offspring. Liver MUFA and PUFA contents decreased in the TG and IG offspring when compared with CG offspring. Liver MUFA content also decreased in the PG offspring. These modifications in FA composition possibly affected liver mitochondrial function, as respiration was impaired in the TG offspring and H2O2 production was higher in the IG offspring. In addition, mitochondrial Ca2+ retention capacity was reduced by approximately 40 and 55 % in the TG and IG offspring, respectively. In conclusion, maternal consumption of trans-unsaturated and interesterified fat affected offspring health by compromising mitochondrial bioenergetics and lipid metabolism in the liver.
Assuntos
Metabolismo Energético , Ácidos Graxos/efeitos adversos , Lactação , Fígado/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Mitocôndrias/metabolismo , Ácidos Graxos trans/efeitos adversos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Glicemia/metabolismo , Cálcio/metabolismo , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/metabolismo , Ácidos Graxos/metabolismo , Ácidos Graxos Monoinsaturados/metabolismo , Ácidos Graxos Insaturados/metabolismo , Feminino , Peróxido de Hidrogênio/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Consumo de Oxigênio , Óleos de Plantas , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Respiração , Ácidos Graxos trans/metabolismo , Triglicerídeos/sangueRESUMO
We investigated whether maternal intake of normolipidic diets with distinct fatty acid (FA) compositions alters the lipidic profile and influences the inflammatory status of the adult offsprings׳ brains. C57BL/6 female mice during pregnancy and lactation received diets containing either soybean oil (CG), partially hydrogenated vegetable fat rich in trans-fatty acids (TG), palm oil (PG), or interesterified fat (IG). After weaning, male offspring from all groups received control diet. The FA profile was measured in the offspring׳s brains at post-natal days 21 and 90. Brain functional capillary density as well as leukocyte-endothelial interactions in the cerebral post-capillary venules was assessed by intravital fluorescence microscopy at post-natal day 90. Inflammation signaling was evaluated through toll-like receptor 4 (TLR4) content in brain of the adult offspring. In the 21-day old offspring, the brains of the TG showed higher levels of trans FA and reduced levels of linoleic acid (LA) and total n-6 polyunsaturated fatty acids (PUFA). At post-natal day 90, TG and IG groups showed reduced levels of eicosapentaenoic acid (EPA) and total n-3 PUFA tended to be lower compared to CG. The offspring׳s brains exhibited an altered microcirculation with increased leukocyte rolling in groups TG, PG and IG and in TG group increased leukocyte adhesion. The TLR4 content of TG, IG and PG groups only tended to increase (23%; 20% and 35%, respectively). Maternal consumption of trans FA, palm oil or interesterified fat during pregnancy and lactation can trigger the initial steps of inflammatory pathways in the brain of offspring in adulthood.
Assuntos
Encéfalo/metabolismo , Ácidos Graxos/metabolismo , Microcirculação/fisiologia , Óleos de Plantas/administração & dosagem , Efeitos Tardios da Exposição Pré-Natal , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Peso Corporal , Encéfalo/anatomia & histologia , Encéfalo/crescimento & desenvolvimento , Dieta , Ingestão de Alimentos , Endotélio/metabolismo , Feminino , Humanos , Leucócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óleo de Palmeira , Gravidez , Óleo de Soja/administração & dosagem , Receptor 4 Toll-Like/metabolismo , Ácidos Graxos trans/administração & dosagemRESUMO
Prenatal and early postnatal nutritional status may predispose offspring to impaired glucose tolerance and changes in insulin sensitivity in adult life. The long-term consequences of changes in maternal dietary fatty acid composition were determined in rats. From day 1 until day 12 of pregnancy, rats were given isocaloric diets containing 9% nonvitamin fat based on soybean, olive, fish (FO), linseed, or palm oil. Thereafter, they were maintained on the standard diet; offspring were studied at different ages. Body weight at 4, 8, and 12 mo and lumbar adipose tissue and liver weights at 12 mo did not differ between females on the different diets, whereas in males the corresponding values were all lower in the offspring from the FO group compared with the other dietary groups. Plasma glucose concentrations (both basal and after an oral glucose load) did not change with sex or dietary group, but plasma insulin concentrations were lower in females than in males and, in males, were lowest in the FO group. Similar relations were found with both the homeostasis model assessment of insulin resistance and insulin sensitivity index. In conclusion, the intake of more n-3 fatty acids (FO diet) during early pregnancy reduced both fat accretion and age-related decline in insulin sensitivity in male offspring but not in females. It is proposed that the lower adiposity caused by the increased n-3 fatty acids during the intrauterine life was responsible of the lower insulin resistance in male offspring.
Assuntos
Envelhecimento/efeitos dos fármacos , Suplementos Nutricionais , Óleos de Peixe/administração & dosagem , Resistência à Insulina/fisiologia , Fenômenos Fisiológicos da Nutrição Pré-Natal , Tecido Adiposo/anatomia & histologia , Tecido Adiposo/efeitos dos fármacos , Envelhecimento/fisiologia , Animais , Glicemia/efeitos dos fármacos , Glicemia/fisiologia , Peso Corporal/efeitos dos fármacos , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Homeostase/efeitos dos fármacos , Homeostase/fisiologia , Insulina/sangue , Masculino , Tamanho do Órgão , Gravidez , Ratos , Fatores SexuaisRESUMO
BACKGROUND: Considering the importance of long chain polyunsaturated fatty acids to fetal development and the lack of studies that have compared the status of fatty acids between adolescents and adults mothers, the purpose of this study was to evaluate the composition of fatty acids in maternal and umbilical cord plasma from adolescent and adults mothers. METHODS: Forty pregnant adolescents and forty pregnant adults were selected to assess the distribution profile of fatty acids in the maternal and umbilical cord plasma. Quantification of fatty acids in the total lipids of the sample groups was performed through the use of gas-liquid chromatography. RESULTS: The maternal and umbilical cord plasma of the adolescents showed a greater concentration of AA than did that of the adults (P < 0.05). However, a greater percentage of EPA was found in the umbilical cord plasma of the adults (P < 0.05). DHA in the plasma of the adolescent mothers correlated positively to birth weight and head circumference. CONCLUSIONS: This suggests that in situations of greater nutritional risk, as in adolescent pregnancy, n-3PUFA concentrations have a greater influence on the proper development of newborns. Moreover, variations in fatty acid concentrations in the maternal and cord plasma of adolescents and adults may indicate that pregnancy affects the LC-PUFA status of adults and adolescents in distinct ways.
Assuntos
Ácidos Graxos Ômega-3/sangue , Ácidos Graxos , Sangue Fetal , Mães/psicologia , Adolescente , Adulto , Antropometria , Peso ao Nascer , Ácidos Graxos/sangue , Ácidos Graxos/química , Feminino , Humanos , Recém-Nascido , GravidezRESUMO
Pregnant rats received soybean (SO), olive (OO), fish (FO) and linseed (LO) oil diets from conception to d12 of gestation (early diets) and standard diet thereafter. At d12 and d20 the lipoprotein lipase (LPL) activity was evaluated in maternal adipose tissues (ATs). Fatty Acid (FA) profile was determined in maternal lumbar AT (LAT), in milk and in pup's plasma and brain. LPL activity was higher in ATs at d12 than d20, all groups presenting hypertriglyceridemia at d20. At d12, the LO diet resulted higher LPL activity and incorporation of 18:3 n-3 into LAT. FA profile in maternal LAT at d20 and colostrum was similar to early diets, reflected also in FA composition of pup's plasma. In FO, brain phospholipids had higher 22:6 n-3 without affecting arachidonic acid. These results suggest that specifics dietary FA in early pregnancy modulates lipid metabolism and the provision of LC-PUFA in milk and pups brain.
Assuntos
Tecido Adiposo/metabolismo , Gorduras na Dieta/metabolismo , Ácidos Graxos/metabolismo , Prenhez/metabolismo , Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Animais , Animais Recém-Nascidos , Gorduras Insaturadas na Dieta/metabolismo , Gorduras Insaturadas na Dieta/farmacologia , Feminino , Óleos de Peixe/farmacologia , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: Our previous study indicated that partially hydrogenated fat (PHF) diets, rich in trans-isomers, alter plasma lipids and increase the lipogenesis rate on adipose tissue in rats at a young age. In the present study we investigated the effects of dietary PHF on the expression of genes associated with glucose and lipid metabolism in rat adipose tissue. METHODS: Female Wistar rats were fed normolipidic diets containing PHF (rich in trans-fatty acids and poor in polyunsaturated fatty acids [PUFAs]), soy oil (rich in omega-6 PUFAs), and fish oil (rich in omega-3 PUFAs) during gestation and lactation; young male pups were fed the same diets from weaning until 120 d of life. The mRNA expression of peroxisome proliferator-activated receptor-gamma, tumor necrosis factor-alpha, resistin, adiponectin, and leptin were analyzed in retroperitoneal adipose tissue (RET) using real time polymerase chain reaction. RESULTS: The PHF group showed the highest triacylglycerol, glucose, and insulin levels and the lowest plasma adiponectin level. The RET of PHF incorporated trans-fatty acids, whereas fish oil and soy oil groups had increased omega-3 and omega-6 PUFAs, respectively. In the RET the PHF group had the highest resistin and tumor necrosis factor-alpha levels and the lowest adiponectin and peroxisome proliferator-activated receptor-gamma gene expressions, whereas the fish oil group had the highest peroxisome proliferator-activated receptor-gamma and the lowest leptin gene expression. CONCLUSION: Prolonged intake of PHF has a negative effect on the expression of genes in RET when compared with diets with omega-6 and omega-3 PUFAs. These changes may be an effect of the smaller proportions of PUFAs in this fat, instead of being only caused by trans-fatty acids.
Assuntos
Adipocinas/metabolismo , Gorduras na Dieta/farmacologia , Ácidos Graxos Insaturados/farmacologia , Expressão Gênica/efeitos dos fármacos , Gordura Intra-Abdominal/efeitos dos fármacos , Adipocinas/genética , Animais , Glicemia , Peso Corporal/efeitos dos fármacos , Gorduras na Dieta/metabolismo , Ácidos Graxos Insaturados/metabolismo , Feminino , Óleos de Peixe/farmacologia , Hidrogenação , Insulina/sangue , Gordura Intra-Abdominal/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , PPAR gama/genética , PPAR gama/metabolismo , Gravidez , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Óleo de Soja/farmacologia , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/metabolismoRESUMO
We have previously shown that adult female rats exposed to intra-uterine malnutrition were normophagic, although obese and resistant to insulin-induced hypophagia. The present study aimed at examining aspects of another important catabolic component of energy homeostasis control, the hypothalamic serotonergic function, which inhibits feeding and stimulates energy expenditure. Pregnant dams were fed ad libitum or were restricted to 50 % of ad libitum intake during the first 2 weeks of pregnancy. Control and restricted 4-month-old progeny were studied. The restricted rats had increased body adiposity with normal daily food intake but failed to respond with hypophagia to an intracerebroventricular injection of serotonin (5-hydroxytryptamine; 5-HT). Stimulation, by food ingestion, of extracellular levels of serotonin in medial hypothalamus microdialysates was more pronounced and lasted longer in the restricted than in the control rats. In the restricted group, hypothalamic levels of 5-HT 2C receptor protein tended to be reduced (P = 0.07) while the levels of 5-HT1B receptor and serotonin transporter proteins were significantly elevated (36 and 79 %, respectively). In conclusion, female rats undernourished in utero had normophagic obesity as adults but had an absence of serotonin-induced hypophagia and low hypothalamic levels of the 5-HT 2C receptor. Compensatory adaptations for the functional serotonergic impairment were evidenced, such as an enhanced release of serotonin in response to a meal allied to up-regulated hypothalamic 5-HT1B and transporter expression. Whether these compensations will persist in later life warrants further investigation. Moreover, it cannot be ruled out that the serotonergic component of energy expenditure was already impaired, thus contributing to the observed body-fat phenotype.
Assuntos
Desnutrição/fisiopatologia , Obesidade/embriologia , Efeitos Tardios da Exposição Pré-Natal , Fenômenos Fisiológicos da Nutrição Pré-Natal/fisiologia , Serotonina/fisiologia , Animais , Peso Corporal/fisiologia , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Feminino , Doenças Fetais/fisiopatologia , Hipotálamo/metabolismo , Microdiálise/métodos , Obesidade/etiologia , Obesidade/fisiopatologia , Gravidez , Ratos , Ratos Wistar , Serotonina/farmacologiaRESUMO
OBJECTIVE: We evaluated whether insulin hypophagia and hypothalamic signaling are affected in adult rats exposed to intrauterine undernutrition. METHODS: Pregnant rats ate ad libitum throughout pregnancy and lactation (control, C) or 50% of control intake in the first 2 wk of pregnancy (restricted, R). Four-month-old C and R progeny received insulin or vehicle intracerebroventricular injections for evaluation of 24-h food intake, hypothalamic insulin receptor (IR), and IR substrate-1 (IRS-1) protein content and tyrosine phosphorylation, pp185 phosphorylation, and IRS-1 association with phosphatidylinositol 3-kinase (PI3-K). RESULTS: With respect to males, R males had normal body composition and insulin-induced hypophagia. IR protein levels were lower but IR phosphorylation was higher in R than in C males. IRS-1 levels and phosphorylation were similar between C and R males, insulin stimulated an IRS-1/PI3-K association in C but not in R males, and pp185 phosphorylation was higher in R than in C males. For females, body fat and serum leptin were elevated in R females. Insulin inhibited food intake in C but not in R females. Insulin-induced IR phosphorylation and protein levels of IR and IRS-1 were higher in R than in C females. However, IRS-1 and pp185 phosphorylation and IRS-1/PI3-K association were significantly stimulated by insulin in C but not in R females. CONCLUSIONS: Female adult rats exposed to intrauterine undernutrition had increased adiposity, marked impairment of hypothalamic insulin signaling, and loss of insulin-induced hypophagia. These disturbances were less severe or even absent in male progeny. The findings show that female progeny are more susceptible than their male siblings to the effects of maternal malnutrition.
Assuntos
Animais Recém-Nascidos/metabolismo , Hipotálamo/fisiopatologia , Insulina/metabolismo , Desnutrição/fisiopatologia , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Receptor de Insulina/metabolismo , Animais , Composição Corporal/fisiologia , Dieta Redutora , Ingestão de Alimentos/fisiologia , Feminino , Hipotálamo/metabolismo , Injeções Intraventriculares , Proteínas Substratos do Receptor de Insulina , Peptídeos e Proteínas de Sinalização Intracelular , Lactação/fisiologia , Masculino , Desnutrição/sangue , Desnutrição/metabolismo , Fosfoproteínas/metabolismo , Fosforilação , Gravidez , Prenhez/metabolismo , Prenhez/fisiologia , Efeitos Tardios da Exposição Pré-Natal , Ratos , Ratos Wistar , Fatores Sexuais , Transdução de Sinais/fisiologiaRESUMO
The purpose of this study was to evaluate the effects of four isoenergetic diets of differing fat composition on blood lipid profile and adiposity in young rats. Diets containing different lipid sources--partially hydrogenated vegetable oil (PHVO), palm oil (PO), canola oil (CO), and soy oil (SO)--were fed to lactating rats during the 21 days of lactation, and then fed to young males following weaning until the 45th day of life. In vivo lipogenesis rate (LR), lipid content (LC), relative level of FA, and the activity of lipoprotein lipase (LPL) enzyme were measured in epididymal adipose tissue (EPI). Fasting blood lipoproteins and LC in the carcass were also appraised. Body weight of PO and PHVO groups was significantly higher than CO and SO groups from day 14 of lactation to day 45, despite the lower food intake in the PHVO group. PO and PHVO groups presented higher LR and LC in EPI than SO and CO groups. Carcass fat content was significantly higher in PHVO and PO groups than in CO and SO groups. The LPL activity in EPI was unaffected by dietary lipids. PHVO group had increased total cholesterol and TAG concentrations in comparison with the PO group, and significantly lower HDL level compared with the other groups. These results show that the kind of FA in the dietary lipid offered early in life can affect lipid metabolism and adiposity.
Assuntos
Adiposidade/fisiologia , Gorduras na Dieta/farmacologia , Ácidos Graxos/fisiologia , Metabolismo dos Lipídeos/fisiologia , Tecido Adiposo/química , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Recém-Nascidos , Peso Corporal , Dieta , Gorduras na Dieta/metabolismo , Ingestão de Alimentos/fisiologia , Ácidos Graxos/química , Feminino , Lactação/fisiologia , Masculino , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , RatosRESUMO
OBJECTIVE: Using rats we examined whether maternal intake of hydrogenated fat rich in trans fatty acids affects brain fatty acid profile, hypothalamic content of insulin receptor and insulin receptor substrate-1 proteins, and the hypophagic effect of centrally administered insulin in 3-mo-old male progeny. METHODS: Throughout pregnancy and lactation, Wistar rats ate isocaloric/normolipidic diets with soybean oil (control) or soybean oil-derived hydrogenated fat (trans diet) as a fat source. Upon weaning, the trans offspring continued on the trans diet (trans group) or were switched to a control diet (trans-control group). RESULTS: Compared with control rats, trans rats had lower brain levels of eicosapentaenoic acid. Compared with trans rats, trans-control rats had increased levels of total polyunsaturated fatty acids and arachidonic acid and decreased levels of trans fatty acids, saturated fatty acids, and monounsaturated fatty acids. Insulin receptor and insulin receptor substrate-1 levels were significantly lower (44% and 38%, respectively) in trans than in control rats. In trans-control rats, insulin receptor was 26% lower (P < 0.05), whereas insulin receptor substrate-1 was 50% lower, than in control rats. Insulin decreased 24-h feeding in control (27%) and trans (38%) rats but failed to do so in trans-control rats. The latter group had increased serum glucose levels. CONCLUSIONS: The data suggest that the early (intrauterine/perinatal) exposure to hydrogenated fat rich in trans fatty acids programmed the hypothalamic feeding control mechanisms. As young adults, only trans-control animals showed loss of insulin-induced hypophagia, indicating that the mismatch between early and later nutritional environments was relevant. However, the trans group also showed signs of altered appetite signaling mechanisms, suggesting that the early adaptations may have deleterious consequences later in life.