Impaired PI 3-kinase activation in adipocytes from early growth-restricted male rats

Ozanne, Susan E.; Dorling, M. W.; Wang, C. L.; Navé, Barbara T.

doi:10.1152/ajpendo.2001.280.3.e534

Cited by 95 publications

(82 citation statements)

References 29 publications

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“…Increased expression of the insulin receptor [22,23,24] has been observed and this reversed with age [25] possibly providing part of the explanation of the change from increased to decreased insulin sensitivity with age.…”

Section: Studies In Vitromentioning

confidence: 97%

For Debate: Fetal and early postnatal growth restriction lead to diabetes, the metabolic syndrome and renal failure*

2003

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Section: Studies In Vitromentioning

confidence: 97%

For Debate: Fetal and early postnatal growth restriction lead to diabetes, the metabolic syndrome and renal failure*

2003

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“…Secondly, they exhibited increased noradrenergic-stimulated lipolysis and a blunted response to insulin-reduced lipolytic action. By contrast, older adult offspring from LP dams underwent an age-related loss of glucose tolerance that paralleled an impaired insulinstimulated PI3K pathway in adipocytes (Ozanne et al 2001). …”

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

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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“…This molecular characterisation demonstrated that insulin receptor expression is not altered in muscle or adipose tissue from old adult offspring that had been growth-restricted at birth, suggesting that, as in the human situation, the molecular basis of the insulin resistance is a post-receptor defect. Two insulin-signalling molecules were expressed at dramatically reduced levels in the offspring with early growth restriction, namely the atypical protein kinase C (PKC), PKCζ [7] and the p110β subunit of phosphatidylinositol (PI) 3-kinase [8,9]. These proteins are both known to be important in mediating the metabolic actions of insulin [10,11].…”

Section: Introductionmentioning

confidence: 99%

Low birthweight is associated with specific changes in muscle insulin-signalling protein expression

et al. 2005

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Aims/hypothesis: People with low birthweight have an increased risk of developing type 2 diabetes mellitus in adulthood. The mechanistic basis of this phenomenon is not known. Here we investigate the effect of early growth restriction on the expression of insulin-signalling proteins in skeletal muscle in a human cohort and a rat model. Methods: We recruited 20 young men with low birthweight (mean birthweight 2702±202 g) and 20 age-matched control subjects (mean birthweight 3801± 99 g). Biopsies were obtained from the vastus lateralis muscle and protein expression of selected insulin-signalling proteins was determined. Rats used for this study were male offspring born to dams fed a standard (20%) protein diet or a low (8%) protein diet during pregnancy and lactation. Protein expression was determined in soleus muscle from adult offspring. Results: Low-birthweight subjects showed reduced muscle expression of protein kinase C (PKC)ζ, p85α, p110β and GLUT4. PKCζ, GLUT4 and p85 were also reduced in the muscle of rats fed a low-protein diet. Other proteins studied were unchanged in low-birthweight humans and in rats fed a low-protein diet when compared with control groups. Conclusions/interpretation: We found decreased expression of specific insulin-signalling proteins in low-birthweight subjects compared to controls. These changes precede the onset of impaired glucose tolerance. The similarity of protein expression profile in the men with low birthweight compared to that of the offspring of rats fed a low-protein diet suggests that the rodent model is an accurate representation of the human situation. It also provides a potential mechanistic explanation as to why the fetal environment plays an important role in determining risk of developing type 2 diabetes.

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Impaired PI 3-kinase activation in adipocytes from early growth-restricted male rats

Cited by 95 publications

References 29 publications

For Debate: Fetal and early postnatal growth restriction lead to diabetes, the metabolic syndrome and renal failure*

For Debate: Fetal and early postnatal growth restriction lead to diabetes, the metabolic syndrome and renal failure*

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

Low birthweight is associated with specific changes in muscle insulin-signalling protein expression

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