Programming of hypothalamic neuropeptide gene expression in rats by maternal dietary protein content during pregnancy and lactation

Cripps, Roselle L.; Martin-Gronert, Malgorzata S.; Archer, Zoe A.; Hales, C. N.; Mercer, Julian G.; Ozanne, Susan E.

doi:10.1042/cs20080393

Cited by 64 publications

(60 citation statements)

References 36 publications

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“…This has been observed in rat and mouse models with bilateral uterine artery ligation or isocalorie low protein nutrition during pregnancy (Simmons et al 2001, Song et al 2008, Cripps et al 2009, Hermann et al 2009). In addition, these data are also supported by human observations (Baker et al 1989, Levy-Marchal & Czernichow 2006.…”

Section: Discussionmentioning

confidence: 99%

Macrophage migration inhibitory factor deficiency leads to age-dependent impairment of glucose homeostasis in mice

Serre‐Beinier

Toso²,

Morel³

et al. 2010

Journal of Endocrinology

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Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine produced by many cells and tissues including pancreatic b-cells, liver, skeletal muscle, and adipocytes. This study investigates the potential role of MIF in carbohydrate homeostasis in a physiological setting outside of severe inflammation, utilizing Mif knockout (MIFK/K) mice. Compared with wild-type (WT) mice, MIFK/K mice had a lower body weight, from birth until 4 months of age, but subsequently gained weight faster, resulting in a higher body weight at 12 months of age. The lower weight in young mice was related to a higher energy expenditure, and the higher weight in older mice was related to an increased food intake and a higher fat mass. Fasting blood insulin level was higher in MIFK/K mice compared with WT mice at any age. After i.p. glucose injection, the elevation of blood insulin level was higher in MIFK/K mice compared with WT mice, at 2 months of age, but was lower in 12-month-old MIFK/K mice. As a result, the glucose clearance during intraperitoneal glucose tolerance tests was higher in MIFK/K mice compared with WT mice until 4 months of age, and was lower in 12-month-old MIFK/K mice. Insulin resistance was estimated (euglycemic-hyperinsulinemic clamp tests), and the phosphorylation activity of AKT was similar in MIFK/K mice and WT mice. In conclusion, this mouse model provides evidence for the role of MIF in the control of glucose homeostasis.

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Section: Discussionmentioning

confidence: 99%

Macrophage migration inhibitory factor deficiency leads to age-dependent impairment of glucose homeostasis in mice

Serre‐Beinier

Toso²,

Morel³

et al. 2010

Journal of Endocrinology

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“…This enabled us to investigate mechanisms mediating the effects of early nutrition on susceptibility to developing diet-induced obesity without the confounding effects of obesity itself. In recent years, leptin has been studied as a key factor involved in programming of obesity risk (Cripps et al, 2009;Bouret, 2004). However, we previously showed that programming of increased adiposity is, at least in part, leptin-independent (Cottrell et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats

et al. 2016

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List of abbreviations5As the prevalence of obesity increases across the globe major efforts are directed at studying the mechanisms involved. Growing evidence suggests that susceptibility to obesity can be programmed by maternal and neonatal nutrition. In particular, individuals with low birth weight that undergo rapid postnatal growth are at higher risk of developing increased adiposity in later life. The molecular mechanisms mediating the interaction between early nutrition and obesity risk are, however, still largely unknown. Currently, there are no pharmacological therapies to prevent the increase in adiposity in individuals that underwent nutritional challenge in early life. Serotonin (5-HT) system is widely recognized as one of the key regulators of food intake and body weight. During fetal life serotonin also acts as a trophic factor that regulates brain development. As compounds targeting endogenous serotonin bioavailability have been among the most clinically effective treatments for obesity (e.g. d-fenfluramine), treatment targeting serotonin system may prevent the development of obesity in at risk individuals. Results:The study has shown that maternal protein restriction increased levels of serotonin in the blood of pregnant rat mums and in the placenta and the fetal brain. In adulthood the offspring had a reduced ability to sense serotonin, which was associated with a reduced hypothalamic expression of 5-HT2Creceptors -the primary serotonin receptor influencing appetite. As expected, reduced 5-HT2Creceptor expression was associated with impaired sensitivity to serotonin-mediated appetite suppression and hence could lead to increases in food intake. On the other hand offspring of low protein dams had a programmed increase in 5-HT2A receptors, which are positioned, just like 5-HT2C receptors, in the arcuate nucleus of the hypothalamus -a key area of the brain, involved in the control of food intake. Moreover, these animals were more sensitive to 5-HT2A receptor agonistinduced appetite suppression. Implications and future directions:This study identified a molecular mechanism that is involved in mediating the effects of suboptimal maternal diet on the regulation of food intake in the offspring. In addition, the authors showed that a treatment with 5-HT2A receptor agonist may potentially prevent the development of obesity in individuals that were exposed in utero to suboptimal nutrition and then underwent rapid postnatal growth. Non-hallucinogenic 5-HT2A receptor agonist should be used for such treatment. Combining the 5-HT2A receptor agonist with 5-HT2CR and 5-HT1BR agonists could potentially further increase the anorectic therapeutic effect. Disease Models & Mechanisms • DMM • Advance article AbstractThough obesity is a global epidemic, the physiological mechanisms involved are little understood.Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low protein diet during pregnancy causes decreased intrauterine growth, rapid...

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“…Weanling rat offspring from LP dams displayed enhanced orexigenic drive (i.e. increased NPY and decreased POMC mRNA expression; Cripps et al 2009). Thus, it may predispose them to hyperphagia and an increased risk of developing obesity later in life, particularly when nourished with a hypercaloric diet.…”

Section: Maternal Reduced Nutritionmentioning

confidence: 99%

The hypothalamus–adipose axis is a key target of developmental programming by maternal nutritional manipulation

Breton¹

2012

Journal of Endocrinology

114

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Epidemiological studies initially demonstrated that maternal undernutrition leading to low birth weight may predispose for energy balance disorders throughout life. High birth weight due to maternal obesity or diabetes, inappropriate early post-natal nutrition and rapid catch-up growth may also sensitise to increased risk of obesity. As stated by the Developmental Origin of Health and Disease concept, the perinatal perturbation of foetus/neonate nutrient supply might be a crucial determinant of individual programming of body weight set point. The hypothalamus-adipose axis plays a pivotal role in the maintenance of energy homoeostasis controlling the nutritional status and energy storage level. The perinatal period largely corresponds to the period of brain maturation, neuronal differentiation and active adipogenesis in rodents. Numerous dams and/or foetus/neonate dietary manipulation models were developed to investigate the mechanisms underlying perinatal programming in rodents. These models showed several common offspring hypothalamic consequences such as impaired neurogenesis, neuronal functionality, nuclei structural organisation and feeding circuitry hardwiring. These alterations led to a persistent reprogrammed appetite system that favoured the orexigenic pathways, leptin/insulin resistance and hyperphagia. Impaired hypothalamic sympathetic outflow to adipose tissue and/or reduced innervation may also account for modified fat cell metabolism. Thus, enhanced adipogenesis and/or lipogenesis capacities may predispose the offspring to fat accumulation. Abnormal hypothalamus-adipose axis circadian rhythms were also evidenced. This review mainly focuses on studies in rodents. It highlights hormonal and epigenetic mechanisms responsible for long-lasting programming of energy balance in the offspring. Dietary supplementation may provide a therapeutic option using a specific regimen for reversing adverse programming outcomes in humans.

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Programming of hypothalamic neuropeptide gene expression in rats by maternal dietary protein content during pregnancy and lactation

Cited by 64 publications

References 36 publications

Macrophage migration inhibitory factor deficiency leads to age-dependent impairment of glucose homeostasis in mice

Macrophage migration inhibitory factor deficiency leads to age-dependent impairment of glucose homeostasis in mice

5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats

The hypothalamus–adipose axis is a key target of developmental programming by maternal nutritional manipulation

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