Metabolic Disorders In Adulthood Research Articles

Maternal Perinatal Undernutrition Drastically Reduces Postnatal Leptin Surge and Affects the Development of Arcuate Nucleus Proopiomelanocortin Neurons in Neonatal Male Rat Pups

A growing body of evidence suggests that maternal undernutrition sensitizes the offspring to the development of energy balance metabolic disorders such as type 2 diabetes, dyslipidemia, and obesity. The present study aimed at examining the impact of maternal undernutrition on leptin plasma levels in newborn male rats and on the arcuate nucleus proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons that are major leptin targets. Using a model of perinatal maternal 50% food-restricted diet (FR50) in the rat, we evaluated leptin plasma levels and hypothalamic POMC and NPY gene expression from postnatal day (PND) 4 to PND30 in both control and FR50 offspring. In control rats, a postnatal peak of plasma leptin was observed between PND4 and PND14 that reached a maximal value at PND10 (5.17 +/- 0.53 ng/ml), whereas it was dramatically reduced in FR50 pups with the higher concentration at PND7 (0.93 +/- 0.23 ng/ml). In FR50 animals, using semiquantitative RT-PCR and in situ hybridization, we showed that the hypothalamic POMC mRNA level was decreased from PND14 until PND30, whereas NPY gene expression was not significantly modified. In PND21 FR50 animals, we observed strikingly reduced immunoreactive beta-endorphin nerve fibers projecting to the hypothalamic paraventricular nucleus without affecting NPY projections. Our data showed that maternal undernutrition drastically reduces the postnatal surge of plasma leptin, disturbing particularly the hypothalamic wiring as well as the gene expression of the anorexigenic POMC neurons in male rat pups. These alterations might contribute to the adult metabolic disorders resulting from perinatal growth retardation.

Predictive value of maternal bodyweight, postnatal weight gain and prenatal dexamethasone overexposure for the development of obesity in adult marmoset monkeys

In rats, adult bodyweight is modulated by the intrauterine environment as well as early postnatal nutritional conditions. Along with fetal glucocorticoid overexposure or postnatal overfeeding persistent increases of bodyweight, blood pressure, liver enzymes (PEPCK) and a decrease in glucose tolerance are observed. Moreover, there is also evidence for a resistance against satiety signals in distinct brain regions. Whether prenatal glucocorticoid overexposure promotes obesity in primates is still matter of debate. We therefore investigated in offspring of marmoset monkeys the effect of intrauterine overexposure with the synthetic glucocorticoid dexamathasone (DEX) either during early or late pregnancy on weight gain, blood pressure and biochemical measures in a two year follow-up study. Marmoset monkeys (Callithrix jacchus) are small (˜400g) non-endangered South American non-human primates. They are of increasing interest in biomedical research because they share many similarities with humans and are easy to handle and to breed under standardized laboratory housing conditions. Three groups of pregnant marmoset monkeys were treated orally for one week with vehicle (CON; N=10) or with dexamethasone (5mg/kg daily) during early (E-DEX; pregnancy day 42–48; N=10) or late pregnancy (L-DEX; pregnancy day 90–96; N=10), respectively. In male offspring (N=30 experimental animals in total) bodyweight was recorded in weekly to monthly intervals. Blood pressure was measured and blood samples were collected at 6, 12, 18 and 24 months of age. Triglycerides, HDL-cholesterol, total cholesterol, fasting glucose, glucose after an oral glucose load (OGTT) and HbA1c were determined. In newborns, weight did not differ between groups. During the first two months after birth L-DEX offspring gained significantly (p<0.02) more weight than E-DEX and CON. In adulthood bodyweight correlated directly with maternal non-pregnant bodyweight (p<0.05) and the weight gain during two months after birth (p=0.01). Metabolic parameters and blood pressure correlated significantly (p<0.005) with bodyweight (negative correlation for HDL-cholesterol, positive correlation for all other parameters). As a consequence, offspring that showed rapid early weight gain and had an obese mother were likely to develop obesity with symptoms of metabolic syndrome, i.e. increased blood pressure, triglycerides, total cholesterol, fasting glucose, HbA1c and decreased HDL-cholesterol. Epidemiological studies in humans are consistent with these results showing that an obese mother and rapid early weight gain are risk factors for the development of obesity in later life. In contrast to the findings in rats, prenatal DEX overexposure seems to play a less important role for bodyweight development in marmosets. Due to the similarities to humans the marmoset monkey seems to be an ideal model for further studies on the regulation of early postnatal weight gain and its role for the development of metabolic disorders in adulthood. Supported by a European Commission Grant (QLRI-CT-2002–02758, EUPEAH).

Early life events and the programming of feeding behavior.

H4H 1R3 Events occurring during the perinatal period can persistently influence the energy storage and expenditure, being associated with an increased incidence of metabolic disorders in adulthood. For instance, studies have shown that low birth weight predicts insulin resistance and type 2 diabetes, hypertension, obesity and cardiovascular disease, especially in cases which postnatal catch-up in body weight during childhood is evidenced. Thus, feeding patterns during the postnatal period and the presence or absence of accelerated postnatal weight gain are crucial mediators of the risk for subsequent obesity, atherosclerosis and cardiovascular disease, as well as insulin resistance. These findings suggest that the feeding behavior during the life course is of critical importance, especially among high-risk children, such as those born at low birth weight. In animal studies, it was demonstrated that perinatal factors can alter food preferences. The voluntary choice for palatable and junk food can be contributing to the increased risk for diseases in adult life after different early experiences. Therefore, the programming of feeding preferences is one possible mechanism linking early life events to the long-term effects on health and metabolism.

Glucocorticoid hormone programming in early-life and its impact on adult health

Traditionally, lifestyle and genetic predisposition are considered to be the main determinants of the common non communicable cardiovascular and metabolic diseases of middle age, such as hypertension, ischemic heart disease and Type 2 diabetes mellitus. However, over the last decade an increasing number of epidemiological studies have suggested that factors operating in early-life are also important determinants of the risk of cardiovascular and metabolic disorders in adulthood. This organizational phenomenon is known as early-life programming. Data from several distinct populations in Europe, Asia, Australia and North America have shown that low birth-weight strongly predicts the subsequent occurrence of hypertension, hyperlipidemia, insulin resistance, Type 2 diabetes and ischemic heart disease deaths in adult life [1]. These relationships are largely independent of traditional adult lifestyle factors (e.g., smoking, adult weight, social class, excess alcohol intake and sedentariness), which are additive risks to the effects of birth weight.

Sport et fonctions métaboliques

Current epidemiological studies emphasize the increased of metabolic diseases of the adults, such as obesity, type-2 diabetes and metabolic syndromes. Even more worrying is the rising prevalence of obesity in children. It is due more to sedentariness, caused more by inactivity (television, video, games, etc.) than by overeating. Many studies have shown that regular physical activities benefit various bodily functions including metabolism. After dealing with the major benefits of physical exercise on some adult metabolic disorders, we focus on the prime role played by physical activity in combating the public health problem of childhood obesity.

Skeletal proportions and metabolic disorders in adults.

The present study investigated the associations of stature, lower leg length (LLL) and demi-arm span (demi-AS) with major predisposing cardiovascular risk factors and coronary heart disease. Cross-sectional study set at Glasgow Royal Infirmary of a subsample of 543 men and 646 women aged 25-66 y from the random MONICA sample. ASSOCIATED MEASURES: LLL, demi-AS, blood pressure, plasma total cholesterol, diabetes mellitus and coronary heart disease (angina, angioplasty, heart attack, and coronary artery bypass graft). The numbers (and proportions) of men and women, respectively, with hypertension were 126 (23.6%) and 80 (14.0%), hypercholesterolaemia 155 (29.0%) and 171 (30.1%), coronary heart disease 53 (10.1%) and 47 (8.4%), and diabetes 15 (2.9%) and 9 (1.6%). Results were adjusted for age, social class and smoking. Analysis of variance showed that in men, shortness of height, LLL or demi-AS were all associated significantly (P < 0.05) with hypercholesterolaemia. Long LLL, high ratios of LLL:height or LLL:demi-As were associated significantly (P < 0.05) with diabetes mellitus. In women, shortness of height or LLL were associated with significantly (P < 0.05) with coronary heart disease. High ratio of demi-AS:height or low ratio of LLL:demi-AS was associated significantly (P < 0.05) with coronary heart disease. Short stature and limb lengths, and also altered skeletal proportions, which may reflect interrupted early growth, are associated with several metabolic disorders. Skeletal disproportion associates with diabetes in men and coronary heart disease in women.