Prenatal influences on leptin sensitivity and susceptibility to diet-induced obesity

Krechowec, Stefan O.; Vickers, Mark H.; Gertler, Arieh; Breier, Bernhard H.

doi:10.1677/joe.1.06679

Cited by 90 publications

(78 citation statements)

References 43 publications

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“…Our present findings also suggest that exposure to prenatal undernutrition results in adult dysregulation of appetite homeostasis and reduced AgRP mRNA expression, possibly via central leptin resistance, which we have previously shown can occur in the absence of obesity and hyperleptinaemia and is associated with increased plasma C-peptide and triglyceride levels (Krechowec et al 2006). We have also demonstrated that, while exposure to prenatal undernutrition can increase food intake, the development of amplified obesity characterised by excessive fat mass accrual requires a critical interaction with postnatal high-fat nutrition.…”

Section: Discussionsupporting

confidence: 79%

Prenatal influences on susceptibility to diet-induced obesity are mediated by altered neuroendocrine gene expression

Ikenasio-Thorpe¹,

Breier²,

Vickers³

et al. 2007

Journal of Endocrinology

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The escalating rates of obesity and type 2 diabetes have reached pandemic proportions. It has been proposed that the risk of developing metabolic disorders in adult life is influenced by environmental factors, which operate during the early periods of development. We have previously shown that an interaction between the prenatal and the postnatal dietary environment amplifies the propensity towards dietinduced obesity, although the mechanisms are unclear. In the present study, we investigated the interaction between prenatal undernutrition and postnatal high-fat nutrition on key genes of the hypothalamic appetite regulatory network. Pregnant Wistar rats were fed a standard chow diet either ad libitum (AD) or at 30% of AD intake throughout gestation (UN). From weaning, female AD and UN offspring were fed either a standard chow (ADC nZ8, UNC nZ8) or a high-fat diet (45% kcal as fat; ADHF nZ8, UNHF nZ8) ad libitum for the remainder of the study. At 24 weeks of age, body composition was assessed by dual energy X-ray absorptiometry analysis and total RNA was extracted from whole rat hypothalami. Real-time PCR was performed to characterise pro-opiomelanocortin (POMC), neuropeptide Y (NPY), agouti-related protein (AgRP) and OBRb gene expression at the mRNA level. Our results demonstrate that the amplification of postnatal obesity develops as a consequence of an interaction between prenatal undernutrition and postnatal high-fat nutrition. This phenotype also shows significant alterations in POMC, NPY, AgRP and OBRb gene expression together with elevations in circulating levels of both plasma leptin and insulin. These findings are consistent with the predictive adaptive response hypothesis that neuroendocrine development during fetal life may be based on predictions about postnatal environmental conditions. Increased susceptibility to diet-induced obesity develops if a mismatch between the anticipated and the actual conditions are encountered.

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Section: Discussionsupporting

confidence: 79%

Prenatal influences on susceptibility to diet-induced obesity are mediated by altered neuroendocrine gene expression

Ikenasio-Thorpe¹,

Breier²,

Vickers³

et al. 2007

Journal of Endocrinology

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show abstract

“…31,33,34,[36][37][38][39][40] Although we did not have data regarding maternal obesity during pregnancy, the odds favouring overweight in children with increasing weight gained during pregnancy was adjusted for the current maternal BMI. As in other studies, [41][42][43][44] we used self-reported height and weight in order to categorize parental BMI, although this measures might not be extremely reliable, because of the low sensitivity of this method to evaluate the prevalence of overweight and obesity.…”

Section: Discussionmentioning

confidence: 99%

Maternal weigh gain during pregnancy and overweight in Portuguese children

et al. 2007

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Objective: The objective of our study was to assess the association between maternal weight gain during pregnancy and childhood overweight. Design: This study was a cross-sectional analysis. Setting: The data were derived from a community-based survey of children from primary schools of Portugal. Subjects: The study was performed in a sample of 6-12-year-old Portuguese school children (2445 girls and 2400 boys; age was 8.570.91 years). Measurements: Height and weight were measured according to international standards, and body mass index (BMI) was calculated. The definition of overweight was based on average centiles according to the International Obesity Task Force cutoffs. Children's parents completed a self-administered questionnaire, which provided information on general family background characteristics, maternal weight gain during pregnancy and children's physical activity. The response rate was 70.6%. Children's dietary intake was measured using a 24-h dietary recall. Logistic regression models were fitted to estimate the magnitude of the association between maternal weight gain during pregnancy and overweight in their children, adjusting for confounders (gender, age, birthweight, order of birth, breastfeeding, smoking during pregnancy, physical activity, parental BMI, parental education, calcium to protein ratio and energy intake). Results: The prevalence of overweight (including obesity) was 29% in boys and 33% in girls. The odds favouring overweight (including obesity) increased significantly for those women who gained X16 kg during pregnancy, compared to those with o9 kg , even after adjustment for confounders (crude odds ratio (OR) ¼ 1.53, confidence interval (CI) 95% 1.27-1.84, P-trend o0.001; Adjusted OR ¼ 1.27, CI 95% 1.01-1.61, P-trend ¼ 0.038). Conclusion: Large maternal weight gain during pregnancy (X16 kg) was significantly associated with higher risk of overweight in Portuguese children.

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“…Many epidemiological studies have indeed demonstrated that infants born small for gestational age are more prone to develop obesity, hypertension and type 2 diabetes in adulthood. [27][28][29] Experimental studies have further corroborated that rodents and other animal species submitted to protein or calorie restriction during gestation and/or suckling exhibit hyperphagia, [30][31][32][33] insulin resistance, 34,35 reduced leptin sensitivity, 36,37 hepatic steatosis, 38 elevated blood pressure 39,40 and hyperlipidemia. 35,37,38 These observations have been explained by the thrifty phenotype hypothesis, also called metabolic programming or the developmental origins of disease.…”

Section: Introductionmentioning

confidence: 93%

Perinatal nutrient restriction induces long-lasting alterations in the circadian expression pattern of genes regulating food intake and energy metabolism

et al. 2010

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Objective: Several lines of evidence indicate that nutrient restriction during perinatal development sensitizes the offspring to the development of obesity, insulin resistance and cardiovascular disease in adulthood via the programming of hyperphagia and reduced energy expenditure. Given the link between the circadian clock and energy metabolism, and the resetting action of food on the circadian clock, in this study, we have investigated whether perinatal undernutrition affects the circadian expression rhythms of genes regulating food intake in the hypothalamus and energy metabolism in the liver. Design: Pregnant Sprague-Dawley rats were fed ad libitum either a control (20% protein) or a low-protein (8% protein) diet throughout pregnancy and lactation. At weaning, pups received a standard diet and at 17 and 35 days of age, their daily patterns of gene expression were analyzed by real-time quantitative PCR experiments. Results: 17-day-old pups exposed to perinatal undernutrition exhibited significant alterations in the circadian expression profile of the transcripts encoding diverse genes regulating food intake, the metabolic enzymes fatty acid synthase and glucokinase as well as the clock genes BMAL1 and Period1. These effects persisted after weaning, were associated with hyperphagia and mirrored the results of the behavioral analysis of feeding. Thus, perinatally undernourished rats exhibited an increased hypothalamic expression of the orexigenic peptides agouti-related protein and neuropeptide Y. Conversely, the mRNA levels of the anorexigenic peptides pro-opiomelanocortin and cocaine and amphetamine-related transcripts were decreased. Conclusion: These observations indicate that the circadian clock undergoes nutritional programming. The programming of the circadian clock may contribute to the alterations in feeding and energy metabolism associated with malnutrition in early life, which might promote the development of metabolic disorders in adulthood.

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Prenatal influences on leptin sensitivity and susceptibility to diet-induced obesity

Cited by 90 publications

References 43 publications

Prenatal influences on susceptibility to diet-induced obesity are mediated by altered neuroendocrine gene expression

Prenatal influences on susceptibility to diet-induced obesity are mediated by altered neuroendocrine gene expression

Maternal weigh gain during pregnancy and overweight in Portuguese children

Perinatal nutrient restriction induces long-lasting alterations in the circadian expression pattern of genes regulating food intake and energy metabolism

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