Maternal hormonal manipulations in rats cause obesity and increase medial hypothalamic norepinephrine release in male offspring

Jones, Alan P.; Pothos, Emmanuel N.; Rada, Pedro; Olster, Deborah H.; Hoebel, Bartley G.

doi:10.1016/0165-3806(95)00078-r

Cited by 66 publications

(54 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…On the other hand, overnutrition during gestation and lactation may program the individual to become obese and insulin-resistant by increasing the number of adipocytes and by producing pancreatic b-cell hyperplasia which results in hyperinsulinaemia, insulin-resistance and increased deposition of lipids in adipose stores (Knittle & Hirsch 1968;Johnson et al 1973). Changes in the metabolic milieu during gestation and lactation in obese dams may also affect the development of offspring central systems involved in the regulation of energy homeostasi, possibly because of exposure to high insulin or leptin levels during the period of brain development ( Jones & Dayries 1990;Plagemann et al 1992a,b;Dorner & Plagemann 1994;Jones et al 1995Jones et al , 1996Ahima et al 1999a;Levin & Dunn-Meynell 2002a-c).…”

Section: Effects Of Altering the Maternal Environment Throughout Gestmentioning

confidence: 99%

Metabolic imprinting: critical impact of the perinatal environment on the regulation of energy homeostasis

Levin

2006

Phil. Trans. R. Soc. B

201

170

View full text Add to dashboard Cite

Epidemiological studies in humans suggest that maternal undernutrition, obesity and diabetes during gestation and lactation can all produce obesity in offspring. Animal models have allowed us to investigate the independent consequences of altering the pre-versus post-natal environments on a variety of metabolic, physiological and neuroendocrine functions as they effect the development in the offspring of obesity, diabetes, hypertension and hyperlipidemia (the 'metabolic syndrome'). During gestation, maternal malnutrition, obesity, type 1 and type 2 diabetes and psychological, immunological and pharmacological stressors can all promote offspring obesity. Normal post-natal nutrition can reduce the adverse impact of some of these pre-natal factors but maternal high-fat diets, diabetes and increased neonatal access to food all enhance the development of obesity and the metabolic syndrome in offspring. The outcome of these perturbations of the perinatal environmental is also highly dependent upon the genetic background of the individual. Those with an obesity-prone genotype are more likely to be affected by factors such as maternal obesity and high-fat diets than are obesity-resistant individuals. Many perinatal manipulations appear to promote offspring obesity by permanently altering the development of central neural pathways, which regulate food intake, energy expenditure and storage. Given their strong neurotrophic properties, either excess or an absence of insulin and leptin during the perinatal period are likely to be effectors of these developmental changes. Because obesity is associated with an increased morbidity and mortality and because of its resistance to treatment, prevention is likely to be the best strategy for stemming the tide of the obesity epidemic. Such prevention should begin in the perinatal period with the identification and avoidance of factors which produce permanent, adverse alterations in neural pathways which control energy homeostasis.

show abstract

Section: Effects Of Altering the Maternal Environment Throughout Gestmentioning

confidence: 99%

Metabolic imprinting: critical impact of the perinatal environment on the regulation of energy homeostasis

Levin

2006

Phil. Trans. R. Soc. B

201

170

View full text Add to dashboard Cite

show abstract

“…42 A similar pattern has been observed in another model in which catchup growth of nutrient-restricted foetuses was induced during the last week of rat gestation. 43,44 In sheep, maternal nutrient restriction over the period of rapid placental growth followed by restoration of maternal nutrition over the second half of gestation enhances the adipose tissue development at the end of gestation, which was thought to increase the risk of obesity in later life. 45 However, this does not lead to significant increase in adipose and fat mass at adulthood.…”

Section: Animal Models For Programming Of Obesitymentioning

confidence: 99%

Programming of obesity and cardiovascular disease

2004

View full text Add to dashboard Cite

BACKGROUND: There is evidence that malnutrition in early life induces a growth retardation leading, in adult life, to manifest components of the metabolic syndrome. However, the impact on obesity seems less clearly established. OBJECTIVE: To review the effects of foetal and postnatal malnutrition on the programming of obesity in the context of the metabolic syndrome, as well as the link between central obesity and cardiovascular diseases. METHODS: Included in the review were recent papers exploring the mechanisms linking maternal nutrition with impaired foetal growth and later obesity, cardiovascular disease, hypertension and diabetes in humans and animals. RESULTS: The programming of obesity during foetal and early postnatal life depends of the timing of maternal malnutrition as well as the postnatal environment. Obesity arises principally in offspring submitted to malnutrition during early stages of gestation and which presented early catch-up growth. The programming may involve the dysregulation of appetite control or the hormonal environment leading to a context favourable to obesity development (hypersecretion of corticosteroids, hyperinsulinaemia and hyperleptinaemia and anomalies in the IGF axis). Adipose tissue secretes actively several factors implicated in inflammation, blood pressure, coagulation and fibrinolysis. The programmed development of intra-abdominal obesity after early growth restriction may thus favour higher prevalence of hypertension and cardiovascular diseases. CONCLUSIONS: Abdominal obesity appears in malnourished offspring and is aggravated by early catch-up growth. Higher rates of intra-abdominal obesity observed after growth restriction may participate to hypertension and create atherothrombotic conditions leading to the development of cardiovascular diseases.

show abstract

“…It is known that amphetamine's effects on behavior are attenuated in diabetic rats (22) and that systemic injections of insulin alter catecholamine neurochemistry (1,3, 17,29). Interactions between DA and other neurotransmitters such as opiate peptides may also play a critical role in elevating drug intake or other behavioral patterns in underweight rats.…”

Section: Dopaminementioning

confidence: 99%

Chronic Food Deprivation Decreases Extracellular Dopamine in the Nucleus Accumbens: Implications for a Possible Neurochemical Link Between Weight Loss and Drug Abuse

1995

View full text Add to dashboard Cite

POTHOS, EMMANUEL N, LUIS HERNANDEZ AND BARTLEY G HOEBELChronicfooddeprivationdecmases extracellular dopamine in the nucleus accumbens: implications forapossibleneurochemicallink betweenweight loss and drug abuse. Obes Res. 1995;3(Suppl4):525S-529S. InratsreducedtoSO% ofnormalbodyweight(n=9),the basal levels of extracellular dopamine (DA) in the nucleus accumbens (NAC), as determined by microdialysis,decmased significantly to 33% (mean f SEM) of their normal baseline (pX.01). BasalextracellullarDA did not change significantly over amatching3-weekperiodin controls (n=7). No changes were observed in NAC serotonin after weight reduction. These results indicate that parts of the mesolimbic DA system are depressed in underweight rats. The observed decrease in basal DA may be responsible for a variety of behavioralchanges observed in undernourished humans and animals including the tendency to eat and gainweight when food becomes available. Given that DA can be released in the NAC when rats self-inject drugs of abuse, the present findings may help explain why animals increase drug intake whenthey areunderweight.

show abstract

Maternal hormonal manipulations in rats cause obesity and increase medial hypothalamic norepinephrine release in male offspring

Cited by 66 publications

References 24 publications

Metabolic imprinting: critical impact of the perinatal environment on the regulation of energy homeostasis

Metabolic imprinting: critical impact of the perinatal environment on the regulation of energy homeostasis

Programming of obesity and cardiovascular disease

Chronic Food Deprivation Decreases Extracellular Dopamine in the Nucleus Accumbens: Implications for a Possible Neurochemical Link Between Weight Loss and Drug Abuse

Contact Info

Product

Resources

About