Developmental changes in embryonic hypothalamic neurons during prenatal fat exposure

Poon, Kinning; Barson, Jessica R.; Fagan, Shawn E.; Leibowitz, Sarah F.

doi:10.1152/ajpendo.00238.2012

Cited by 27 publications

(53 citation statements)

References 62 publications

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“…Rats exposed in utero to a high-fat diet compared to a balanced diet show in adolescence and adulthood higher gene expression and peptide levels of OX (Chang, Gaysinskaya, Karatayev, & Leibowitz, 2008; Poon, Barson, Fagan, & Leibowitz, 2012). This increase in endogenous OX in prenatally-exposed animals is accompanied by an increase in the intake of calories of standard chow and also by a higher preference for the high-fat diet (Chang et al, 2008).…”

Section: Role Of Orexin/hypocretin In Non-homeostatic Intakementioning

confidence: 99%

Orexin/Hypocretin System: Role in Food and Drug Overconsumption

Barson

Leibowitz

2017

International Review of Neurobiology

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The neuropeptide orexin/hypocretin (OX), while largely transcribed within the hypothalamus, is released throughout the brain to affect complex behaviors. Primarily through the hypothalamus itself, OX homeostatically regulates adaptive behaviors needed for survival, including food intake, sleep-wake regulation, mating, and maternal behavior. However, through extra-hypothalamic limbic brain regions, OX promotes seeking and intake of rewarding substances of abuse, like palatable food, alcohol, nicotine, and cocaine. This neuropeptide, in turn, is stimulated by the intake of or early life exposure to these substances, forming a non-homeostatic, positive feedback loop. The OX receptor involved in these behaviors, adaptive behavior or substance seeking and intake, is dependent on the particular brain region that contributes to them. Thus, we propose that, while the primary function of OX is to maintain arousal for the performance of adaptive behaviors, this neuropeptide system is readily coopted by rewarding substances that involve positive feedback, ultimately promoting their abuse.

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Section: Role Of Orexin/hypocretin In Non-homeostatic Intakementioning

confidence: 99%

Orexin/Hypocretin System: Role in Food and Drug Overconsumption

Barson

Leibowitz

2017

International Review of Neurobiology

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“…The dams were individually housed in a fully accredited AAALAC facility (22°C, with a 12:12-h light-dark cycle with lights off at 12 pm). The rats were split into 2 groups of 8 dams each and maintained ad libitum from E7 on either a high-fat diet (HFD; 5.02 kcal/g) with 50% fat or a standard lab chow (3.36 kcal/g) with 13% fat (Purina, St. Louis, MO), as previously described (Dourmashkin et al, 2006, Chang et al, 2008, Poon et al, 2012). In the HFD group, standard lab chow was available for the first 3 days (until E9) before being completely removed, in order for the HFD group to overcome neophobia and adapt to the HFD.…”

Section: Methodsmentioning

confidence: 99%

“…There was no difference between the HFD and chow dams in their daily caloric intake during pregnancy (70–90 kcals). Dams were sacrificed on embryonic day 19 (E19), as previously described (Poon et al, 2012). The whole hypothalamus was extracted and dissociated for plating into cell culture, as previously described (Poon et al, 2012, Poon et al, 2013), or placed in either RNAlater for mRNA purification.…”

Section: Methodsmentioning

confidence: 99%

“…Dams were sacrificed on embryonic day 19 (E19), as previously described (Poon et al, 2012). The whole hypothalamus was extracted and dissociated for plating into cell culture, as previously described (Poon et al, 2012, Poon et al, 2013), or placed in either RNAlater for mRNA purification. Whole hypothalamus was used since individual regions of the hypothalamus are not fully differentiated at this age.…”

Section: Methodsmentioning

confidence: 99%

“…The standard lab chow diet (3.36 kcal/g) consisted of 13% fat and was acquired from Purina (St. Louis, MO), and the HFD used in this report has been described in detail in previous publications (Dourmashkin et al, 2006, Chang et al, 2008, Poon et al, 2012). Briefly, the HFD consisted of 50% fat composed of 75% lard (Armour Star, Peoria, IL) and 25% vegetable oil (Crisco, Orrville, OH), of 25% carbohydrate composed of 30% dextrin (ICN Pharmaceuticals, Costa Mesa, CA), 30% cornstarch (ICN Pharmaceuticals, Costa Mesa, CA), and 40% sucrose (Domino Foods Inc., Yonkers, NY), and of 25% protein from casein (Bio-Serv, Frenchtown, NJ), and it was supplemented with minerals (USP XIV Salt Mixture Briggs; ICN Pharmaceuticals, Costa Mesa, CA) and vitamins (Vitamin Diet Fortification Mixture; ICN Pharmaceuticals, Costa Mesa, CA).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Prenatal fat-rich diet exposure alters responses of embryonic neurons to the chemokine, CCL2, in the hypothalamus

Poon

Abramova

et al. 2016

Neuroscience

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Maternal consumption of a high fat diet (HFD) during pregnancy is found to stimulate the genesis of hypothalamic orexigenic peptide neurons in the offspring, while HFD intake in adult animals produces a systemic low-grade inflammation which increases neuroimmune factors that may affect neurogenesis and neuronal migration. Building on this evidence and our recent study showing that the inflammatory chemokine, CCL2, stimulates the migration of hypothalamic neurons and expression of orexigenic neuropeptides, we tested here the possibility that prenatal exposure to a HFD affects this chemokine system, both CCL2 and its receptors, CCR2 and CCR4, and alters its actions on hypothalamic neurons, specifically those expressing the neuropeptides, enkephalin (ENK) and galanin (GAL). Using primary dissociated hypothalamic neurons extracted from embryos on embryonic day 19, we found that prenatal HFD exposure compared to chow control actually reduces the expression of CCL2 in these hypothalamic neurons, while increasing CCR2 and CCR4 expression, and also reduces the sensitivity of hypothalamic neurons to CCL2. The HFD abolished the dose-dependent, stimulatory effect of CCL2 on the number of migrated neurons and even shifted its normal stimulatory effect on migrational velocity and distance traveled by control neurons to an inhibition of migration. Further, it abolished the dose-dependent, stimulatory effect of CCL2 on neuronal expression of ENK and GAL. These results demonstrate that prenatal HFD exposure greatly disturbs the functioning of the CCL2 chemokine system in embryonic hypothalamic neurons, reducing its endogenous levels and ability to promote the migration of neurons and their expression of orexigenic peptides.

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Maternal obesity induced by a high fat diet causes altered cellular development in fetal brains suggestive of a predisposition of offspring to neurological disorders in later life

et al. 2013

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Fetal development in an obese maternal intrauterine environment has been shown to predispose the offspring for a number of metabolic disorders in later life. The observation that a large percentage of women of child-bearing age in the US are overweight/obese during pregnancy is therefore a source of concern. A high fat (HF) diet-induced obesity in female rats has been used as a model for maternal obesity. The objective of this study was to determine cellular development in brains of term fetuses of obese rats fed a HF diet from the time of weaning. Fetal brains were dissected out on gestational day 21 and processed for immunohistochemical analysis in the hypothalamic as well as extra-hypothalamic regions. The major observation of this study is that fetal development in the obese HF female rat induced several alterations in the HF fetal brain. Marked increases were observed in orexigenic signaling and a significant decrease was observed for anorexigenic signaling in the vicinity of the 3rd ventricle in HF brains. Additionally, our results indicated diminished proliferation and maturation of stem-like cells in the hypothalamus (3rd ventricular region) as well as in the cortex. The results from the present study indicate developmental alterations in the hypothalamic and extra-hypothalamic regions in the HF fetal brain suggestive of a predisposition for the development of obesity and possibly neurodevelopmental abnormalities in the offspring.

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Developmental changes in embryonic hypothalamic neurons during prenatal fat exposure

Cited by 27 publications

References 62 publications

Orexin/Hypocretin System: Role in Food and Drug Overconsumption

Orexin/Hypocretin System: Role in Food and Drug Overconsumption

Prenatal fat-rich diet exposure alters responses of embryonic neurons to the chemokine, CCL2, in the hypothalamus

Maternal obesity induced by a high fat diet causes altered cellular development in fetal brains suggestive of a predisposition of offspring to neurological disorders in later life

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