RESUMO
BACKGROUND: While the adverse metabolic effects of exposure to obesogenic diets during both the prenatal and early postnatal period are well established, the relative impact of exposure during these separate developmental windows remains unclear. This study aimed to assess the relative contribution of exposure to a maternal cafeteria diet during pregnancy and lactation on body weight, fat mass and expression of lipogenic and adipokine genes in the offspring. METHODS: Wistar rats were fed either a control chow (Control, n = 14) or obesogenic cafeteria diet (CAF, n = 12) during pregnancy and lactation. Pups were cross-fostered to another dam in either the same or different dietary group within 24 h of birth. Body weight, body fat mass and expression of lipogenic and adipokine genes in subcutaneous and visceral adipose tissues were determined in offspring at weaning and 3 weeks post-weaning. RESULTS: Offspring suckled by CAF dams had a lower body weight (P < 0.05), but ~ 2-fold higher percentage body fat at weaning than offspring suckled by Control dams (P < 0.01), independent of whether they were born to a Control or CAF dam. At 6 weeks of age, after all offspring were weaned onto standard chow, males and females suckled by CAF dams remained lighter (P < 0.05) than offspring suckled by Control dams, but the percentage fat mass was no longer different between groups. Sterol Regulatory Element Binding Protein-1c (SREBP-1c) mRNA expression was ~ 25% lower in offspring suckled by cafeteria dams in males at weaning (P < 0.05) and in females at 6 weeks of age (P < 0.05). Exposure to a cafeteria diet during the suckling period alone also resulted in increased adipocyte Peroxisome Proliferator Activated Receptor-γ (PPAR-γ) mRNA expression in females, and adiponectin and leptin mRNA expression in both sexes at weaning. CONCLUSIONS: The findings from this study point to the critical role of the suckling period for deposition of adipose tissue in rodents, and the potential role of altered adipocyte gene expression in mediating these effects.
RESUMO
Most individuals whose growth was restricted before birth undergo accelerated or catch-up neonatal growth. This is an independent risk factor for later metabolic disease, but the underlying mechanisms are poorly understood. This study aimed to test the hypothesis that natural and experimentally induced in utero growth restriction increase neonatal appetite and milk intake. Control (CON) and placentally restricted (PR) ewes carrying multiple fetuses delivered naturally at term. Outcomes were compared between CON (n=14) and PR (n=12) progeny and within twin lamb pairs. Lamb milk intake and feeding behaviour and ewe milk composition were determined using a modified weigh-suckle-weigh procedure on days 15 and 23. PR lambs tended to have lower birth weights than CON (-15%, P=0.052). Neonatal growth rates were similar in CON and PR, whilst heavier twins grew faster in absolute but not fractional terms than their co-twins. At day 23, milk protein content was higher in PR than CON ewes (P=0.038). At day 15, PR lambs had fewer suckling bouts than CON lambs and in females light twins had more suckling attempts than their heavier co-twins. Birth weight differences between twins positively predicted differences in milk intakes. Lactational constraint and natural prenatal growth restriction in twins may explain the similar milk intakes in CON and PR. Within twin comparisons support the hypothesis that prenatal constraint increases lamb appetite, although this did not increase milk intake. We suggest that future mechanistic studies of catch-up growth be performed in singletons and be powered to assess effects in each sex.
Assuntos
Animais Lactentes/fisiologia , Peso ao Nascer/fisiologia , Comportamento Alimentar/fisiologia , Retardo do Crescimento Fetal/metabolismo , Tamanho da Ninhada de Vivíparos/fisiologia , Placenta/fisiologia , Animais , Animais Recém-Nascidos , Tamanho Corporal/fisiologia , Feminino , Masculino , Leite/fisiologia , Gravidez , OvinosRESUMO
Clinical studies have reported beneficial effects of a maternal low glycaemic index (GI) diet on pregnancy and neonatal outcomes, but the impact of the diet on the offspring in later life, and the mechanisms underlying these effects, remain unclear. In this study, Albino Wistar rats were fed either a low GI (n=14) or high GI (n=14) diet during pregnancy and lactation and their offspring weaned onto either the low or high GI diet. Low GI dams had better glucose tolerance (AUC[glucose], 1322±55 v. 1523±72 mmol min/l, P<0.05) and a lower proportion of visceral fat (19.0±2.9 v. 21.7±3.8% of total body fat, P<0.05) compared to high GI dams. Female offspring of low GI dams had lower visceral adiposity (0.45±0.03 v. 0.53±0.03% body weight, P<0.05) and higher glucose tolerance (AUC[glucose], 1243±29 v. 1351±39 mmol min/l, P<0.05) at weaning, as well as lower hepatic PI3K-p85 mRNA at 12 weeks of age. No differences in glucose tolerance or hepatic gene expression were observed in male offspring, but the male low GI offspring did have reduced hepatic lipid content at weaning. These findings suggest that consuming a low GI diet during pregnancy and lactation can improve glucose tolerance and reduce visceral adiposity in the female offspring at weaning, and may potentially produce long-term reductions in the hepatic lipogenic capacity of these offspring.
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Previous studies have demonstrated that exposure to a maternal cafeteria diet during the lactation period alone produces detrimental effects to offspring metabolic health comparable to exposure during the entire perinatal period. The present study used a rodent model to assess the effect of a maternal cafeteria diet on the fat content and fatty acid composition of the dams' milk, and to determine the degree to which this was related to the fatty acid status of offspring on postnatal day 1 (PND1), weaning and 3 weeks post-weaning onto a standard rodent diet. As expected, omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) content of both the milk and pup red blood cells (RBCs) was lower in the cafeteria (CAF) group on PND1. At 2 weeks post-partum, milk produced by CAF dams had a higher total fat, saturated fat and n-6 PUFA content, however these differences were modest in comparison with the differences in maternal intake between groups. Offspring suckled by CAF dams had a lower n-3 LCPUFA and n-6 PUFA status at weaning and higher trans fatty acid levels at both weaning and 6 weeks of age. These findings indicate that the fat content and fatty acid composition of the dam's milk is altered by exposure to a cafeteria diet. While it appears that the dam has a significant capacity to buffer the transfer of most dietary lipids into the milk, the trans fatty acids in particular appear to be readily transferred, resulting in persistent increases in trans fatty acid status of the offspring after weaning. The potential physiological implications of this warrants further examination.
Assuntos
Eritrócitos/química , Ácidos Graxos/análise , Lactação/metabolismo , Leite/química , Animais , Ácidos Graxos Ômega-3/metabolismo , Feminino , Humanos , Masculino , Modelos Animais , Ratos , DesmameRESUMO
We have previously reported that the opioid receptor blocker, naloxone, is less effective in reducing palatable food intake in offspring exposed to a maternal cafeteria diet during the perinatal period, implicating a desensitization of the central opioid pathway in the programming of food preferences. The present study aimed to investigate the effect of a maternal cafeteria diet and naloxone treatment on the development of the mesolimbic reward pathway and food choices in adulthood. We measured mRNA expression of key components of the reward pathway (mu-opioid receptor, proenkephalin, tyrosine hydroxylase, D1 and D2 receptors and the dopamine active transporter (DAT)) in the nucleus accumbens (NAc) and ventral tegmental area (VTA) of the offspring of control and cafeteria fed (JF) dams at weaning and after a 10-day naloxone treatment post-weaning and determined food preferences in adulthood in the remaining offspring. Naloxone treatment decreased the expression of DAT by 8.2 fold in female control offspring but increased it by 4.3 fold in female offspring of JF dams relative to the saline-injected reference groups. Proenkephalin mRNA expression was higher in the NAc of female JF offspring compared to controls, independent of naloxone treatment (P<0.05). There was no effect of naloxone treatment on food preferences in adulthood in either control or JF offspring. These data indicate that prenatal exposure to a cafeteria diet alters the impact of opioid signaling blockade in the early post-weaning period on gene expression in the central reward pathway in a sex specific manner, but that these changes in gene expression do not appear to have any persistent impact on food preferences in adulthood.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Caracteres Sexuais , Área Tegmentar Ventral/efeitos dos fármacos , Animais , Dieta Hiperlipídica/efeitos adversos , Sacarose Alimentar/efeitos adversos , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Encefalinas/genética , Encefalinas/metabolismo , Comportamento Alimentar , Feminino , Preferências Alimentares/efeitos dos fármacos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores Dopaminérgicos/genética , Receptores Dopaminérgicos/metabolismo , RecompensaRESUMO
Exposure to a maternal junk food (JF) diet in utero and during the suckling period has been demonstrated to increase the preference for palatable food and increase the susceptibility to diet-induced obesity in adult offspring. We aimed to determine whether the effects of prenatal exposure to JF could be ameliorated by cross-fostering offspring onto dams consuming a standard rodent chow during the suckling period. We report here that when all offspring were given free access to the JF diet for 7 weeks from 10 weeks of age, male offspring of control (C) or JF dams that were cross-fostered at birth onto JF dams (C-JF, JF-JF), exhibited higher fat (C-C: 12.3 ± 0.34 g/kg/day; C-JF: 14.7 ± 1.04 g/kg/day; JF-C: 11.5 ± 0.41 g/kg/day; JF-JF: 14.0 ± 0.44 g/kg/day; P < 0.05) and overall energy intake (C-C: 930.1 ± 18.56 kJ/kg/day; C-JF: 1029.0 ± 82.9 kJ/kg/day; JF-C: 878.3 ± 19.5 kJ/kg/day; JF-JF: 1003.4 ± 25.97 kJ/kg/day; P < 0.05) than offspring exposed to the JF diet only before birth (JF-C) or not at all (C-C). Female offspring suckled by JF dams, despite no differences in food intake, had increased fat mass as percentage of body weight (C-C: 19.9 ± 1.33%; C-JF: 22.8 ± 1.57%; JF-C: 17.4 ± 1.03%; JF-JF: 22.0 ± 1.0%; P < 0.05) after 3 weeks on the JF diet. No difference in fat mass was observed in male offspring. These findings suggest that the effects of prenatal exposure to a JF diet on food preferences in females and susceptibility to diet-induced obesity in males can be prevented by improved nutrition during the suckling period.
RESUMO
One of the major contributing factors to the continuous rise in obesity rates is the increase in caloric intake, which is driven to a large extent by the ease of access and availability of palatable high-fat, high-sugar 'junk foods'. It is also clear that some individuals are more likely to overindulge in these foods than others; however, the factors that determine an individual's susceptibility towards the overconsumption of palatable foods are not well understood. There is growing evidence that an increased preference for these foods may have its origins early in life. Recent work from our group and others has reported that in utero and early life exposure to these palatable foods in rodents increased the offspring's preference towards foods high in fat and sugar. One of the potential mechanisms underlying the programming of food preferences is the altered development of the mesolimbic reward system, a system that plays an important role in driving palatable food intake in adults. The aim of this review is to explore the current knowledge of the programming of food preferences, a relatively new and emerging area in the DOHAD field, with a particular focus on maternal overnutrition, the development of the mesolimbic reward system and the biological mechanisms which may account for the early origins of an increased preference for palatable foods.