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Effects of early overnutrition and undernutrition in rats on the metabolic responses to overnutrition in later life.

Weanling rats fed a palatable "cafeteria" diet consumed 40-70% more energy than stock fed controls but also showed a marked (80%) increase in energy expenditure (diet-induced thermogenesis) so that body weight and body energy gain were almost identical in both groups. Animals previously fed the cafeteria diet for 30 days after weaning exhibited lower weight gains when re-exposed to the cafeteria diet at 90 days of age than either naive rats or rats which had been fed the cafeteria diet continuously from weaning. Rats which had been undernourished for 30 days form weaning and allowed to recover for 30 days showed similar responses to the cafeteria diet as normal animals. Hypertrophy of brown adipose tissue (BAT) was seen in all cafeteria fed rats but hyperplasia (increased DNA content) was observed only in rats which had been overfed in early life. These results suggest that overfeeding young, weanling rats can result in a lower fat content, a greater thermogenic capacity and resistance to obesity later in life and may be due to a permanent increase in BAT cell number.

Adipose Tissue, Brown↗

Overnutrition induced decrease in insulin action for glucose storage: in vivo and in vitro in man.

The effect of short-term overnutrition on insulin action for glucose disposal was assessed in 15 Southwest American Indians (mean wt = 74 +/- 6 kg). After two weeks of weight maintenance and again after two weeks of 62% greater caloric intake (constant ratio of fat:carbohydrate:protein), insulin action for glucose disposal was measured using the euglycemic clamp technique with plasma insulin concentrations of about 110 and 1800 uU/mL. Simultaneous indirect calorimetry was used to estimate carbohydrate oxidation and storage rates. Following overnutrition, mean weight gain was 3.0 +/- 0.2 kg, P less than 0.01. Overnutrition induced a decrease in glucose storage at the low and high insulin concentrations: 1.2 +/- 0.3 to 0.2 +/- 0.3, P less than 0.01, and 6.4 +/- 0.3 to 4.3 +/- 0.5, mg/kg FFM min, P less than 0.001. Carbohydrate oxidation was significantly increased at both insulin concentrations. The mean total insulin mediated glucose disposal rate decreased from 11.6 +/- 0.5 to 10.3 +/- 0.7, P less than 0.01, at the high insulin concentration. This decrease was due entirely to the reduction in carbohydrate storage and was correlated with increased fasting insulin concentration (r = 0.7, P less than 0.01). Overnutrition also induced a significant decrease in the percent muscle glycogen synthase active measured fasting and at the end of the high-dose insulin infusion. The results indicate that short-term overnutrition results in reduced insulin action for glucose storage and disposal which is correlated with increased fasting insulin concentrations. Reduced glycogen synthase activity may contribute to the effect of overnutrition on in vivo insulin-mediated glucose storage.

Adolescent↗

The role of triiodothyronine-induced substrate cycles in the hepatic response to overnutrition: thyroid hormone as an antioxidant.

Overnutrition, by generating reactive oxygen species (ROS), produces oxidative stress - an important cause of cellular injury. In the liver, overnutrition begins in the perivenous hepatocytes. To prevent injury, cells must protect themselves against ROS accumulation. Overnutrition also activates the enzyme deiodinase-1 (D1), which catalyzes the conversion of T4 to T3. D1 is primarily located in the PV region of the liver. Thyroid hormone is known to generate substrate cycling. The hypothesis of this paper is that a nutrient-induced increase in intracellular T3 acts as an antioxidant by inducing substrate cycles that reduce ROS accumulation. These cycles do this by: (i) reducing ROS formation by hydrolyzing excess ATP, thus enhancing oxidative phosphorylation and reducing the proton motive force on the electron transport chain (ETC), and; (ii) enhancing the removal (reduction) of ROS by producing the NADPH required for regeneration of reduced glutathione, a potent endogenous antioxidant. Oxidative stress is an important factor in the etiology of a number of hepatic injuries, including nonalcoholic steatohepatitis (NASH) and hepatocarcinogenesis. In the latter, the frequency of mutations in thyroid hormone receptors (TRs) supports the concept that thyroid hormone acts as a tumor suppressor by reducing oxidative stress. This paper reviews the substrate cycles involved in this process. It also describes other mechanisms that permit rapid availability of T3 to cells undergoing oxidative stress.

Antioxidants↗

Carcinogens in the diet vs. overnutrition. Individual dietary habits, malnutrition, and genetic susceptibility modify carcinogenic potency and cancer risk.

Chemical carcinogens in the diet cannot explain the cancer incidence attributed by epidemiologists to dietary factors when the calculation is based on average exposure levels and conservative estimates of carcinogenic potencies. In a previous review, the discrepancy was explained primarily by overnutrition to which a carcinogenic potency was assigned from dietary restriction experiments and the associated reduction in spontaneous tumor incidence (W.K. Lutz and J. Schlatter, Chemical carcinogens and overnutrition in diet-related cancer, Carcinogenesis 13 [1992] 2211-2216). Here, additional aspects are introduced. They focus on using individual rather than averaged data, both for exposure and susceptibility. First, under conditions of a sublinear (convex) dose-response, the cancer incidence obtained by using an average exposure level is lower than if individual exposure levels associated with particular dietary habits are taken into account. Second, carcinogenic factors, including those unrelated to the diet (e.g., smoking), can act synergistically. Third, the potency of dietary carcinogens is increased under conditions of malnutrition in the sense of a deficiency of protective factors, such as those available with fruits, vegetables, and fibers. Quantitatively, this aspect may be particularly important because it simultaneously increases the efficacy of a multitude of carcinogens. It is concluded that chemical carcinogens could be as important as overnutrition for diet-related cancer.

Alcohol Drinking↗

Nutritional status of 11-12-year-old Jamaican children: coexistence of under- and overnutrition in early adolescence.

OBJECTIVE: To determine the nutritional status of a cohort of 11-12 year olds and ascertain social and demographic factors associated with under- and overweight in early adolescence. DESIGN: Cross-sectional. SUBJECTS: Subgroup (n = 1698) of the birth cohort (September-October 1986) of the Jamaican Perinatal Survey enrolled in schools in the Kingston Metropolitan area. One thousand and sixty-three parents or caregivers provided social and demographic information. RESULTS: Undernutrition and overnutrition are of public health significance among adolescent Jamaican children. Ten per cent of 11-12 year olds had body mass index (BMI) values below the 5th percentile (boys, 10.6%; girls, 7.1%) but this prevalence is relatively low compared with other developing countries. The prevalence of stunting was low (3%). The prevalence of overweight (BMI > or = 85th percentile) (19.3%) was approaching prevalence rates found in the USA. Similar social and demographic variables were associated with thinness and fatness in males. Birth weight predicted overweight in girls. CONCLUSIONS: Under- and overnutrition in early adolescence are important problems in Jamaica. There is a need to address both under- and overnutrition in adolescence in preventive and rehabilitative intervention programmes.

Birth Weight↗

Patterns, distribution, and determinants of under- and overnutrition: a population-based study of women in India.

BACKGROUND: Little systematic evidence exists for the relation between socioeconomic position and nutritional status in countries experiencing the simultaneous presence of under- and overnutrition. OBJECTIVE: We investigated the socioeconomic distribution of nutritional status in India and whether state-level macroeconomic factors modify the relation between socioeconomic position and nutritional status. DESIGN: Our analysis was based on a nationally representative sample of 77 220 women from India, with multiple categories of body mass index (BMI; in kg/m2) as the outcome, namely, <18.5 (underweight), 23-24.9 (pre-overweight), 25-29.9 (overweight), or > or =30 (obese), with 18.5-22.9 as the reference category. RESULTS: In adjusted models, being underweight was inversely related to socioeconomic position, whereas socioeconomic position was positively related to being pre-overweight, overweight, and obese, and the socioeconomic gradient was most marked for obesity. State-level measures of affluence did not modify the positive association between socioeconomic position and categories of overweight. The risk of underweight was lower in affluent states, but this was seen mainly in women of high socioeconomic position. CONCLUSIONS: Undernutrition and overnutrition are epidemics of the impoverished and the affluent, respectively, in India, and this association is consistent at the individual and ecologic levels. Policies should focus on the complex patterns of social distribution of both under- and overnutrition in the Indian context.

Adolescent↗

Chemical carcinogens and overnutrition in diet-related cancer.

The intake of known dietary carcinogens was compiled and the cancer risk was estimated on the basis of carcinogenic potencies in animals as derived from the Carcinogenic Potency Database by Gold and co-workers. The total cancer risk was compared with the number of cancer cases attributed by epidemiologists to dietary factors (one-third of all cancer cases, i.e. approximately 80,000 per one million lives). Except for alcohol, the known dietary carcinogens could not account for more than a few hundred cancer cases. This was seen both with the DNA-reactive carcinogens (heterocyclic aromatic amines, polycyclic aromatic hydrocarbons, N-nitroso compounds, estragole, aflatoxin B1, ethyl carbamate, to name the most important factors) as well as with those carcinogens which have not been shown to react with DNA (e.g. caffeic acid and the carcinogenic metals arsenic and cadmium). Residues and contaminants turned out to be negligible. Among the various possibilities to explain the discrepancy we investigated the role of overnutrition. Dietary restriction in animals is well known for its strong reducing effect on spontaneous tumor formation. These data can be used to derive a carcinogenic potency for excess macronutrients: the tumor incidence seen with the restricted animals is taken as a control value and the increased tumor incidence in the animals fed ad libitum is attributed to the additional feed intake. For excess standard diet in rats, a carcinogenic potency TD50 of 16 g/kg/day was deduced from a recent study. Overnutrition in Switzerland, estimated to be 5.5 kcal/kg/day, was converted to excess food (1.9 g/kg/day) and the cancer incidence was calculated. The result, 60,000 cancer cases per one million lives, is provocatively close to the number of cases not explained by the known dietary chemical carcinogens. Mechanistic studies will be required to test our hypothesis and investigate the role of different types of macronutrients in overnutrition.

Carcinogens↗

Nutrition, overnutrition, and obesity in the first year of line in Malmö, Sweden.

The feeding pattern, calorie intake, weight and height were studied at various ages during the first 12 months in 243 infants born in Sweden. The feeding pattern and calorie intake was close to that recommended. 0-6% in each age group were found to be obese (20-40% above the standard weight) and 15-23% overweight (10-20% above the standard weight). The mean calorie intake during the months before and when obesity and overweight were diagnosed exceeded the normal by 10% or less. When re-examined at age 2 plus or minus 1/2 years, 50% of those children obese up to 1 year remained so, and only 2 earlier overweight had become obese. 25% of the obese children had one obese parent, compared with 10% of the normal children and overweight ones. The low incidence of overnutrition and the low freqency of obese and overweight infants in this study compared with previous studies support the idea that high calorie intake is of importance in the development of obesity during infancy. Accordingly, overnutrition seems to be one factor, in the multifactorial aetiology of obesity, and reduction of overnutrition can reduce, but not abolish, infantile obesity. Whether the reduction of this will subsequently prevent adult obesity remains to be proved.

Body Height↗

Overnutrition in prenatal and neonatal life: a problem?

In most areas of the world nutritional problems are related to quantitative and qualitative deficiencies. However, in North America the possible harmful effects of overnutrition deserve careful consideration.Little information is available concerning overnutrition during prenatal and neonatal life. The author draws attention to this possibility by outlining clinical and biochemical disorders occurring in the newborn which are related to excessive ingestion of calories, fat, protein, vitamins and minerals before and after birth. Particular reference is made to the ingestion of nutritional substances during pregnancy in amounts that are relatively innocuous to the mother but may be harmful to the infant in utero.Further research in this interesting field is needed in an attempt to assess the effect on the fetus of qualitative overnutrition during pregnancy.

Female↗

Body composition and body weight: criteria of overnutrition.

The terms "body weight" and "body composition" are by no means synonymous, and attention is increasingly being focused on body composition. A measurement of relative fatness is a better criterion of caloric overnutrition than is body weight.The simple technique of skinfold measurement using established standard methods is the most practical for use in the field to obtain an estimate of fatness or caloric overnutrition. The current need is for the establishment of "norms" for skinfolds for population groups of all ages and both sexes. When these are established, excellent simple criteria for overnutrition will be available.Prior to the establishment of norms, more work is needed to indicate which skinfolds for each age group and for each sex best reflect total body fatness. Body fatness may then be studied in relation to body weight and both may be related to morbidity, mortality and longevity. Finally, the answer may be obtained to the question whether it is overweight per se or overfatness that is related to excess morbidity and mortality.

Adolescent↗

Hypoadiponectinemia: a common basis for diseases associated with overnutrition.

Adiponectin is a plasma protein derived from adipose tissue, which we discovered from a human adipose cDNA project. Adiponectin exists in circulating plasma at concentrations ranging from 4 to 30 microg/mL, which is much higher than the concentrations of various other hormones and cytokines. Adiponectin has a sticky nature, binding to collagen I, III, and V, which are present in vascular intima. Adiponectin exhibits various antiatherogenic effects on vascular cells, suppressing the expression of adhesion molecules in vascular endothelial cells, proliferation of smooth muscle cells, and cholesteryl-ester accumulation in macrophages. However, its plasma levels are low in subjects with excess intra-abdominal fat. Adiponectin also has antidiabetic properties, and plasma adiponectin levels correlate positively with insulin sensitivity. Several clinical studies have demonstrated that hypoadiponectinemia is a risk factor for new-onset diabetes. Recent studies suggest that hypoadiponectinemia may partly contribute to the development of salt-sensitive hypertension and hypertensive heart failure, and can be also a risk factor for overnutrition-related cancers such as breast, colon, uterine, and prostate cancers. Hypoadiponectinemia might be at least in part the molecular basis of various diseases associated with overnutrition.

Adiponectin↗

Epidemiologic evidence for the fetal overnutrition hypothesis: findings from the mater-university study of pregnancy and its outcomes.

The fetal overnutrition hypothesis proposes that greater maternal adiposity results in increased obesity throughout life in the offspring. The authors examined the associations between parental prepregnancy body mass index (BMI; weight (kg)/height (m)(2)), based on height and weight reported by the mother at her first antenatal clinic visit, and offspring BMI (height and weight measured at age 14 years) in 3,340 parent-offspring trios from a birth cohort based in Brisbane, Australia (mothers were recruited in 1981-1984). The maternal-offspring BMI association was stronger than the paternal-offspring BMI association. In the fully adjusted model, the increase in standardized offspring BMI at age 14 for a one-standard-deviation (SD) increase in maternal BMI was 0.362 SD (95% confidence interval: 0.323, 0.402), and the corresponding result for a one-SD increase in paternal BMI was 0.239 SD (95% confidence interval: 0.197, 0.282). There was statistical support for a difference in the magnitude of the association between maternal-offspring BMI and paternal-offspring BMI in all confounder-adjusted models tested (all p's < 0.0001). In sensitivity analyses taking account of different plausible levels of nonpaternity (up to 15%), the greater maternal effect remained. These findings provide some support for the fetal overnutrition hypothesis.

Adolescent↗

Influence of postnatal overnutrition and pregnancy on non-insulin dependent diabetes induced in Wistar rats by neonatal streptozotocin.

Wistar rats with non-insulin dependent diabetes induced by neonatal streptozotocin (STZ) administration were raised either in large or in small litters. The STZ-treated rats from small litters showed a higher body weight as well as increased blood glucose levels compared with vehicle- and STZ-treated rats reared in large nests at an age of 8 weeks. The higher body weight of these rats was maintained until an age of 15 weeks, whereas the basal blood glucose was normalized. However, both STZ-treated groups exhibited an impaired glucose tolerance. During pregnancy only the glucose tolerance of the STZ-treated animals from large nests was improved although not normalized. The STZ-treated rats from small nests failed to adapt to pregnancy because the blood glucose levels after glucose load were similar to values found in the virgin state. The body weight of pregnant STZ treated rats raised in small litters was significantly lower than in vehicle- or STZ-terated rats from large nests. The number of fetuses per litter was similar in all groups tested. Compared with the vehicle-treated rats from large litters the fetal body weight of STZ-treated rats from small nests was decreased and that of STZ rats raised in large litters was increased. These results suggest that the rats with the more impaired glucose tolerance produce growth-retarded pups and, conversely, rats with rather mild impairment have bigger fetuses than the vehicle-treated ones. In the present study we have examined for the first time the combined effects of postnatal overnutrition and pregnancy on glucose homeostasis of rats treated neonatally with STZ. Our data demonstrate that postnatal overnutrition is an aggravating factor in the development of a diabetic state in these rats, especially at times when the insulin requirement is higher such as puberty and pregnancy.

Animal Nutritional Physiological Phenomena↗

Overnutrition and undernutrition as modifiers of metabolic processes in disease states.

Both overnutrition and undernutrition affect energy metabolism, with overnutrition raising energy expenditure and undernutrition lowering it. Fever is a powerful stimulator of thermogenesis. In diseases such as cancer, AIDS, diabetes mellitus, and rheumatoid arthritis, whether energy expenditure is increased or decreased often depends on how advanced the disorder is. Early on, when the greater protein turnover characteristic of these conditions is paramount, energy expenditure is increased. In addition, in diseases such as cancer, AIDS, and rheumatoid arthritis in which cytokines are released, the cytokines' thermogenic effect initially increases the metabolic rate. However, as the disease becomes more advanced and leads to cachexia, energy expenditure drops below normal. Acute conditions such as burns and trauma significantly raise energy expenditure, primarily by increasing sympathetic response and the release of catecholamines, which are powerful stimulators of energy expenditure.

Acquired Immunodeficiency Syndrome↗

Undernutrition and overnutrition in the neonatal rat: long-term effects on noradrenergic pathways in brain regions.

To determine whether neonatal nutrition influences development of CNS noradrenergic systems, litter sizes were manipulated at birth to produce undernutrition (16-17 pups/litter) or overnutrition (five to six pups) and compared to rats reared in normal litter sizes (10-11 pups). Studies were conducted throughout the preweaning period in which nutrition was manipulated, as well as during postweaning nutritional rehabilitation. Sparing of brain growth occurred, evidenced by much smaller changes in brain region wt than in body wt. Similarly, neonatal malnutrition produced major deficits in norepinephrine levels in peripheral sympathetic pathways, but levels in the brain remained within normal limits. Development of [3H]norepinephrine synaptosomal uptake, a biochemical index for presynaptic terminals, was unimpaired by malnutrition; indeed, higher uptake values were seen than in the control population. Nevertheless, norepinephrine turnover was severely attenuated during nutritional restriction and the effect persisted into adulthood; the deficit was greater in the cerebral cortex than in the cerebellum, despite the fact that cerebellar growth showed less sparing. Development of binding capabilities of noradrenergic receptors, particularly the alpha 2- and beta-subtypes, were also adversely affected in cerebral cortex, again suggestive of a deleterious effect on synaptic function. Animals exposed to neonatal overnutrition showed only slight effects on brain region wt or norepinephrine levels, but did display some suppression of [3H]norepinephrine synaptosomal uptake and enhancement of norepinephrine turnover; changes in receptor binding capabilities in the overnourished animals were attributable to the small alterations in brain region wt. These data indicate that neonatal nutrition alters presynaptic and postsynaptic markers of noradrenergic function that remain abnormal even when nutritional rehabilitation occurs.

Animal Nutritional Physiological Phenomena↗

Thyroxine-binding prealbumin, overnutrition and apolipoprotein A1.

Thyroxine-binding prealbumin (TBPA) seems to be more useful than other biochemical markers for the detection of subclinical protein-energy malnutrition. Accordingly, one can question whether its sensitivity to nutritional supply could be used in healthy populations for the discrimination of groups with low or high energy intakes; if such were the case, could TBPA serve as an index of overnutrition? In order to answer these questions, we measured TBPA circulating levels in three groups of healthy French subjects from a working population, with relatively low, medium or high levels of energy intake. We also observed the correlations of this protein with nutrient intakes and with some biological parameters related to the general nutritional status of the subjects. The observed figures did not support the hypothesis that TBPA could be used to discriminate healthy subjects with relatively low or high energy intake nor as an index of overnutrition. This study disclosed a positive relation of TBPA with alcohol consumption and related parameters such as body mass index or gamma-glutamyl transferase as well as a negative one with alpha 2-globulin and gamma-globulin. Other investigators have found similar results in chronic alcoholics, surgical patients, or patients suffering from severe illnesses such as cancer. Here, the study population consisted of adult men, neither undernourished nor suffering from any severe pathology and who could not be considered excessive drinkers. Positive relations were also observed between TBPA and apolipoprotein A1 and HDL cholesterol levels, which are negatively associated with coronary heart disease risk.

Adult↗

[Energy balance in repeated under- and overnutrition in model studies in sows].

In a model experiment eight adult sows were used to examine the effect of successive periods of under- and oversupply of energy (MUMU) on thermogenesis and efficiency of energy utilization in comparison to a constant maintenance supply (NNNN). Each treatment sequence was assigned to each animal according to a change-over design over 8 weeks. Before and after the treatment periods all the animals were fed at maintenance level (N). Energy deficiency (M) was performed by use of a basal diet with 45% of maintenance energy requirements and values for all the other nutrients sufficient for requirements. Normal (N) and excessive (U) intakes of energy was provided with supplements of starch. The total inake of gross energy during the periods MUMU was exactly the same as during NNNN. Complete energy balances were performed for each animal and period as well as during the pre- and post-experimental phase. There was no or little response of altered energy intake on carbon and energy excretion in faeces, urine and methane. However, heat production was significantly decreased by 4.1% on energy deficiency, and increased by 15.1% during energy oversupply. Summed up over the total sequence the animals produced 5.4% more heat on MUMU than during NNNN. This response was associated with a mobilization of 1.1 MJ/d tissue energy and a decrease in body weight by 2.0 kg. The efficiency of utilization of ME was 88% with energy undersupply and 75% during overnutrition. Criteria of energy balance did not differ between the pre- and post-treatment periods. It could be demonstrated that the increase in energy expenditure at oversupply was entirely explainable by the so-called obligatory thermogenesis. At the energy deficiency periods the efficiency of energy utilization reflected both energy costs of ingestion and processing of nutrients as well as a slight reduction in metabolic rate. Finally, there were no residual effects of the treatment on the energy expenditure of the animals at the end of the experiment.

Animal Feed↗

Predicting under- and overnutrition among women of reproductive age: a population-based study in central Java, Indonesia.

OBJECTIVES: To evaluate changes over 1 year in weight and body mass index (BMI) among a population-based sample of non-pregnant women in Indonesia and to identify risk factors for developing under- and overnutrition. DESIGN: Cross-sectional studies in 1996 and 1997 in the same population. SETTING: Purworejo District, central Java, Indonesia. SUBJECTS: Non-pregnant women (n = 4132) aged 15-49 years of age who participated in both 1996 and 1997. Based on BMI, women were classified as having chronic energy deficiency (CED), and as being either of normal weight or obese. RESULTS: The mean height of the women was below the fifth percentile of international standards. In 1996, 16.2% had CED, 72.2% were normal and 11.6% were obese. In 1997, the corresponding figures were 14.4%, 71.2% and 14.3%, respectively, revealing a significant mean increase in weight and BMI. Among women classified as normal in 1996, 3.0% developed CED in 1997. Significant risk factors for developing CED were experiences of child deaths and non-use of contraceptives. Among women classified as normal in 1996, 5.3% developed obesity in 1997. Here, significant risk factors included most indicators of wealth as well as occupation. CONCLUSIONS: The results should be important for future efforts to prevent CED and obesity in the general population; conditions which are both associated with health risks.

Adolescent↗