Maternal insulin manipulations in rats organize body weight and noradrenergic innervation of the hypothalamus in gonadally intact male offspring

Jones, Alan P.; Olster, Deborah H.; States, Beatrice

doi:10.1016/s0165-3806(96)00128-9

Cited by 40 publications

(37 citation statements)

References 26 publications

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“…While controversial (159), some studies suggest that insulin might cross the placenta to enter the fetal circulation in humans (332). For example, in rats, insulin injections in third trimester dams predispose to adult obesity in offspring (232). However, maternal hyperinsulinemia might increase transplacental glucose transport to the fetus (378).…”

Section: Insulinmentioning

confidence: 99%

Gene-Environment Interactions Controlling Energy and Glucose Homeostasis and the Developmental Origins of Obesity

Bouret

Levin

Ozanne

2015

Physiological Reviews

143

103

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LBouret S, Levin BE, Ozanne SE. Gene-Environment Interactions Controlling Energy and Glucose Homeostasis and the Developmental Origins of Obesity. Physiol Rev 95: 47-82, 2015; doi:10.1152/physrev.00007.2014.-Obesity and type 2 diabetes mellitus (T2DM) often occur together and affect a growing number of individuals in both the developed and developing worlds. Both are associated with a number of other serious illnesses that lead to increased rates of mortality. There is likely a polygenic mode of inheritance underlying both disorders, but it has become increasingly clear that the pre-and postnatal environments play critical roles in pushing predisposed individuals over the edge into a disease state. This review focuses on the many genetic and environmental variables that interact to cause predisposed individuals to become obese and diabetic. The brain and its interactions with the external and internal environment are a major focus given the prominent role these interactions play in the regulation of energy and glucose homeostasis in health and disease.

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Section: Insulinmentioning

confidence: 99%

Gene-Environment Interactions Controlling Energy and Glucose Homeostasis and the Developmental Origins of Obesity

Bouret

Levin

Ozanne

2015

Physiological Reviews

143

103

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“…First, adult rat offspring from gestational dams injected with insulin exhibited enhanced neurite outgrowth of noradrenergic fibres in the PVN (Jones et al 1996). Secondly, post-natally intrahypothalamically insulin-treated rats that became overweight in adulthood exhibited hypotrophic neuronal nuclei within the VMN and DMN (Plagemann et al 1999c).…”

Section: Circulating Factorsmentioning

confidence: 99%

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

Breton¹

2012

Journal of Endocrinology

113

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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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“…For example, rat pups from mothers fed a high-fat diet during gestation cross fostered to dams consuming a low-fat diet during lactation became more obese than pups whose mothers consumed a low-fat diet during gestation and were cross fostered to female rats consuming a high-fat diet during lactation (Levin 2006). Animal studies have revealed that malnutrition (Jones et al 1984), insulin injections (Jones et al 1996), and maternal stress, such as injection of endotoxins and immunosuppressants during gestation, also predispose offspring to adult obesity (Levin 2006). The composition and volume of maternal milk are also important determinants of the development of metabolic regulation (Levin 2006).…”

Section: Animal Models Of Obesitymentioning

confidence: 99%

Relevance of animal models to human eating disorders and obesity

2008

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Background and rationale This review addresses the role animal models play in contributing to our knowledge about the eating disorders anorexia nervosa (AN) and bulimia nervosa (BN) and obesity. Objectives Explore the usefulness of animal models in complex biobehavioral familial conditions, such as AN, BN, and obesity, that involve interactions among genetic, physiologic, psychological, and cultural factors. Results and conclusionsThe most promising animal model to mimic AN is the activity-based anorexia rodent model leading to pathological weight loss. The paradigm incorporates reward elements of the drive for activity in the presence of an appetite and allows the use of genetically modified animals. For BN, the sham-feeding preparation in rodents equipped with a gastric fistula appears to be best suited to reproduce the postprandial emesis and the defects in satiety. Animal models that incorporate genes linked to behavior and mood may clarify biobehavioral processes underlying AN and BN. By contrast, a relative abundance of animal models has contributed to our understanding of human obesity. Both environmental and genetic determinants of obesity have been modeled in rodents. Here, we consider single gene mutant obesity models, along with models of obesigenic environmental conditions. The contributions of animal models to obesity research are illustrated by their utility for identifying genes linked to human obesity, for elucidating the pathways that regulate body weight and for the identification of potential therapeutic targets. The utility of these models may be further improved by exploring the impact of experimental manipulations on the behavioral determinants of energy balance.

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Maternal insulin manipulations in rats organize body weight and noradrenergic innervation of the hypothalamus in gonadally intact male offspring

Cited by 40 publications

References 26 publications

Gene-Environment Interactions Controlling Energy and Glucose Homeostasis and the Developmental Origins of Obesity

Gene-Environment Interactions Controlling Energy and Glucose Homeostasis and the Developmental Origins of Obesity

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

Relevance of animal models to human eating disorders and obesity

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