Gestational weight gain by reduced brain melanocortin activity affects offspring energy balance in rats

Heinsbroek, A. C. M.; Dijk, van Jitse

doi:10.1038/ijo.2008.211

Cited by 5 publications

(3 citation statements)

References 52 publications

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“…While our observation of a loss of response to α‐MSH during pregnancy seems quite clear, these data are not supported by a previous study using chronic third‐cerebral ventricular infusion of SHU9119, a melanocortin‐3,4 receptor blocker. That study found that SHU9119 administered from day 4 of pregnancy significantly increased food intake and weight gain during pregnancy, suggesting that there is ongoing melanocortin tone (Heinsbroek & van Dijk, ). It seems likely that this apparent contradiction is explained by the different timing in the two experiments.…”

Section: Discussionmentioning

confidence: 99%

Attenuated hypothalamic responses to α‐melanocyte stimulating hormone during pregnancy in the rat

Ladyman

Augustine

Scherf

et al. 2016

The Journal of Physiology

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Key pointsr Increased appetite and weight gain occurs during pregnancy, associated with development of leptin resistance, and satiety responses to the anorectic peptide α-melanocyte stimulating hormone (α-MSH) are suppressed.r This study investigated hypothalamic responses to α-MSH during pregnancy, using c-fos expression in specific hypothalamic nuclei as a marker of neuronal signalling, and in vivo electrophysiology in supraoptic nucleus (SON) oxytocin neurons, as a representative α-MSH-responsive neuronal population that shows a well-characterised α-MSH-induced inhibition of firing.r While ICV injection of α-MSH significantly increased the number of c-fos-positive cells in the paraventricular, supraoptic, arcuate and ventromedial hypothalamic nuclei in non-pregnant rats, this response was suppressed in pregnant rats. Similarly, SON oxytocin neurons in pregnant rats did not demonstrate characteristic α-MSH-induced inhibition of firing that was observed in non-pregnant animals.r Given the known functions of α-MSH in the hypothalamus, the attenuated responses are likely to facilitate adaptive changes in appetite regulation and oxytocin secretion during pregnancy.Abstract During pregnancy, a state of positive energy balance develops to support the growing fetus and to deposit fat in preparation for the subsequent metabolic demands of lactation. As part of this maternal adaptation, the satiety response to the anorectic peptide α-melanocyte stimulating hormone (α-MSH) is suppressed. To investigate whether pregnancy is associated with changes in the response of hypothalamic α-MSH target neurons, non-pregnant and pregnant rats were treated with α-MSH or vehicle and c-fos expression in hypothalamic nuclei was then examined. Furthermore, the firing rate of supraoptic nucleus (SON) oxytocin neurons, a known α-MSH responsive neuronal population, was examined in non-pregnant and pregnant rats following α-MSH treatment. Intracerebroventricular injection of α-MSH significantly increased the number of c-fos-positive cells in the paraventricular, arcuate and ventromedial hypothalamic nuclei in non-pregnant rats, but no significant increase was observed in any of these regions in pregnant rats. In the SON, α-MSH did induce expression of c-fos during pregnancy, but this was significantly reduced compared to that observed in the non-pregnant group. Furthermore, during pregnancy, SON oxytocin neurons did not demonstrate the characteristic α-MSH-induced inhibition of firing rate that was observed in non-pregnant animals. Melanocortin receptor mRNA levels during pregnancy were similar to non-pregnant animals, suggesting that receptor down-regulation is unlikely to be a mechanism underlying the attenuated responses to α-MSH during pregnancy. Given the known functions of α-MSH in the hypothalamus, the attenuated responses will facilitate adaptive changes in appetite regulation and oxytocin secretion during pregnancy.

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Section: Discussionmentioning

confidence: 99%

Attenuated hypothalamic responses to α‐melanocyte stimulating hormone during pregnancy in the rat

Ladyman

Augustine

Scherf

et al. 2016

The Journal of Physiology

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“…Leptin is an anorexigenic hormone secreted by adipose tissue and the placenta, but its main function is in the hypothalamus, decreasing appetite and food intake (42). Heinsbroek and van Dijk (43) showed in rats that brain melanocortin receptor blockade during pregnancy induced GWG and increased the body weight of offspring postnatally; the melanocortin receptor blockade can alter leptin and anorexigenic effects in rats, leading to postnatal obesity (44). In addition to rat models, a mouse model has supported the hypothesis that a high-fat diet in obese female mice can alter both adiposity and DNA hypomethylation of inflammation-associated genes in offspring (45).…”

Section: Discussionmentioning

confidence: 99%

Maternal and Early Childhood Determinants of Women's Body Size in Midlife: Overall Cohort and Sibling Analyses

Ester

Houghton

Lumey

et al. 2017

American Journal of Epidemiology

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Observational evidence suggests that adult body size has its roots earlier in life, yet few life-course studies have data on siblings with which to control for family-level confounding. Using prospective data from the Early Determinants of Mammographic Density Study (n = 1,108; 1959-2008), we examined the association of maternal prepregnancy body mass index (BMI; weight (kg)/height (m)2), gestational weight gain (GWG), birth size, and childhood growth factors with adult BMI in daughters at midlife using quantile, linear, and logistic regression models. We compared overall cohort findings (n = 1,108) with sibling differences (n = 246 sibling sets). Results derived by all 3 regression methods supported positive and independent associations of prepregnancy BMI, GWG, and percentile change in early childhood growth with BMI in daughters at midlife. Sibling analyses demonstrated that higher GWG was independently related to a higher adult BMI in daughters, particularly for the highest 90th quantile of adult BMI (β = 0.64 (standard error, 0.26) BMI units). Greater increases in weight percentiles between 1 and 4 years of age within siblings were also associated with higher adult BMI in the 75th quantile (β = 0.06 (standard error, 0.03) kg). Thus, even after consideration of the role of family-level fixed effects, maternal GWG and childhood weight gain are associated with adult body size in midlife.

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“…A simple increases in body weight gain during pregnancy and lactation due to hyperphagia induced by pharmacological inhibition of melanocortin 3/4 receptor leads to the development of obesity in offspring over time (Heinsbroek et al, 2009). Animal study suggests that overnutrition either starting prior to gestation or from gestation and lactation exert similar effect on the development of obesity and hyperinsulinemia in offspring (Howie et al, 2008), suggesting the critical windows of fetal development that determines the phenotype.…”

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confidence: 99%

Overnutrition in Mothers and Appetite Regulators in Offspring

Chen¹,

Morris

2011

Handbook of Behavior, Food and Nutrition

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The World Health Organization (WHO) formally recognized the obesity epidemic in 1997; however, as obesity continues to rise exponentially, it has now reached pandemic proportions. Increasingly around the world, obesity is no longer restricted to adults. Childhood obesity is currently rising at an alarming rate, with 20 million children under five estimated as overweight in 2005 (WHO, 2006). In the USA, the number of overweight children has doubled and the number of overweight adolescents has tripled since 1980 (WHO, 2003). It is increasingly accepted that obesity results from a combination of genetic and environmental factors. Impact of maternal nutrition on the risk of energy metabolic disorders in offspring Overconsumption of energy-rich food and a sedentary lifestyle make significant contributions to the rising rate of childhood obesity. However, apart from the social and environmental factors that influence children's behaviour (Nielson et al., 2006), the prenatal maternal condition is also critical to offspring body composition, and can predispose the fetus to the development of obesity after birth (Forsum et al., 2006). Increasing evidence suggests that both maternal phenotype and nutritional state during gestation and postnatal phase are important in promoting obesity in offspring. Human studies suggest that intrauterine factors may be more important than genetic factors in changing gene expression in response to high-fat diet, which may have a longstanding influence postnatally. Early research revealed the inverse relationship between low birth weight due to gestational malnutrition and the increased risks of obesity and cardiovascular disease (

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Gestational weight gain by reduced brain melanocortin activity affects offspring energy balance in rats

Cited by 5 publications

References 52 publications

Attenuated hypothalamic responses to α‐melanocyte stimulating hormone during pregnancy in the rat

Attenuated hypothalamic responses to α‐melanocyte stimulating hormone during pregnancy in the rat

Maternal and Early Childhood Determinants of Women's Body Size in Midlife: Overall Cohort and Sibling Analyses

Overnutrition in Mothers and Appetite Regulators in Offspring

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