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Circulating hyaluronan levels in the rodent: effects of age and diet.

Circulating hyaluronan (HA) levels were investigated as a function of age and diet in Fischer 344 male rats. A biphasic pattern of age-related changes was observed in rats fed ad libitum a diet in which the protein source was soya/fish meal. HA levels in 3- to 6- and 22- to 29-mo-old rats were not statistically different. However, HA levels in 12- to 20-mo-old rats were 10-29% of the levels in younger or aged adults. HA levels were also measured in rats fed ad libitum a semisynthetic diet in which the protein source was hydrolyzed casein. Whereas the two colonies exhibited similar biphasic age-related changes, HA levels differed 4- to 20-fold at every age examined. Caloric restriction affected HA levels in 19-mo-old casein-fed rats; HA levels were 2.3 times higher than age-matched controls and were not statistically different from young or aged animals. Serum and plasma HA levels were identical in the same individuals at all ages tested. These data suggest that HA turnover and metabolism in the rat are affected by age, dietary composition, and caloric intake.

Aging↗

[Nutritional knowledge of patients in the hypertension clinic. An evaluation using the "Nutrition IQ'].

In this study the nutritional knowledge of 117 patients attending a hypertension clinic was evaluated with the use of the 'Nutrition IQ' questionnaire developed by the National Heart Lung, and Blood Institute. Overweight was identified as a risk factor for hypertension by 98% of the subjects, but more than 10% of the subjects did not identify weight reduction as an important therapeutic tool in the control of hypertension. Around 30% of the patients misjudged the importance of weight reduction in the treatment of hypertension as compared to a low salt diet. 25% believed that a salt reduction will always normalise hypertension. Only 5% of the subjects failed to identify exercise and caloric restriction as the major strategies for weight control. More than two thirds of the patients believed that skipping meals is the best way to reduce energy intake. Carbohydrates were wrongly identified as the major factor for weight gain by 50% of the subjects. The same patients did not recognize reduction in fat intake as the major nutritional tool to maintain or reduce weight. Only 25% of the subjects knew that polyunsaturated fatty acids do have the same caloric content per weight as saturated fatty acids. The nutrition IQ questionnaire can be used as an easy and quick screening method of the nutritional knowledge of patients in a hypertension clinic. The data confirm that there is still a large gap between the knowledge of a certain nutritional (risk) factor and its implementation in daily life, and suggest that patient education should be targeted more on life-style issues.

Adult↗

Obesity prevention in children: opportunities and challenges.

OBJECTIVE: Longitudinal survey data from a number of countries confirm that the number of overweight children continues to increase at alarming rates, and even developing countries are experiencing a rise in their overweight population. There is ample consensus that prevention strategies are essential to turn the tide of the obesity epidemic, and yet there are still relatively few proven prevention approaches for children. This paper briefly discusses some of the common features of childhood obesity prevention programs, focusing on the experience in the US and Canada. APPROACH: Most prevention programs include at least one of the following components: dietary changes, physical activity, behavior and social modifications, and family participation. School-based prevention programs may also include elements related to the school environment and personnel. Primary prevention programs cannot usually restrict caloric intake, but may effectively reduce the energy intake by reducing the energy density of foods, increasing offering of fresh fruits and vegetables, using low-calorie versions of products, and reducing offering of energy-dense food items. Physical activity interventions have recently focused more on reducing inactive time, particularly television viewing. Results from recent studies have reported success in reducing excess weight gain in preadolescents by restricting TV viewing. SUMMARY: Integrating all the activities of a multi-component prevention intervention, and delivering and sustaining it in different environments, continues to be a major challenge for health professionals as well as for parents, educators, and children themselves. Still, encouraging progress has been made in several areas, and the increased awareness of the problem of childhood obesity by all concerned will continue to foster our efforts in this area.

Child↗

Obesity.

Obesity is not a single disease, but a variety of conditions resulting from different mechanisms and associated with various types and degrees of risks. To determine who should lose weight, how much weight should be lost, and how to undertake weight loss, the following types of information are needed: personal-demographic data, developmental patterns, family history, energy balance, body composition/fat distribution, psychological/behavioral measures, endocrine/metabolic measures, complications and associated conditions. Weight reduction should be undertaken by women with morbid obesity, with complications secondary to the obesity, with a strong family history of conditions associated with obesity, or with increased abdomen:hip ratios. In contrast, women who have excess weight localized in the hips and thighs and no personal or family history of associated conditions may not benefit from dietary restriction. Low calorie diets result in adaptive changes, "designed" to prolong survival in the face of famine. These include changes in water balance, metabolic rate, and appetite. Metabolic rate declines, allowing the individual to burn fewer and fewer calories. Each time a woman diets she tends to lose weight less rapidly than the time before. "Restrained eating" predisposes binge eating. Indeed, bulimia rarely occurs in the absence of prior caloric restrictions. Current medical definitions of obesity do not consider these nuances. Existing definitions "over-diagnose" obesity in women, in general, and in older women and nonwhite women, in particular. For example, by existing standards, more than 60 percent of black women more than 45 years of age are considered obese. In contrast, the health risks of similar degrees of obesity are substantially greater for men than for women. Part of the problems lies in the fact that many women have pear-shaped fat distribution,a pattern which is not associated with increased health risks.Current cultural definitions of obesity for women distort the picture even further. In the past 20 years,there has been a progressive decline in the weight-for height of such "culture models" as Playboy centerfold subjects and Miss America contestants. Attempting to achieve such low weights predisposes women to an endless cycle of dieting and regaining, and contributes to the growing problems of eating disorders, including anorexia nervosa and bulimia.

Diet, Reducing↗

The effect of dietary cholesterol, energy intake, and oxygen consumption on cholesterol metabolism in the chick.

This experiment, involving 320 chicks, was conducted to determine the effects of dietary cholesterol, restricted caloric intake, and genetic lines on cholesterol metabolism in the bird. The two lines of chicks studied had been divergently selected for oxygen consumption and had been shown to differ significantly (P less than .01) in weight gain and carcass lipid deposition. The dietary treatments, administered for a 2-week period, consisted of two levels of dietary cholesterol (none and supplemented) for each of two levels of energy (ad libitum and restricted). At the end of this 2-week period, the birds were injected intravenously with 1-14C-acetate and their livers removed 4 hr later. Hepatic cholesterol and lipid synthesis were measured by the uptake of acetate. Added dietary cholesterol significantly (P less than .01) decreased hepatic cholesterol synthesis, lipid synthesis, and specific activity of hepatic cholesterol but increased plasma and liver cholesterol. However, the elevation in plasma and liver cholesterol represented only .9 and 1.8% respectively, of the increase in total intake of dietary cholesterol. Metabolizable energy of diets fed ad libitum was also significantly (P less than .01) reduced with supplemented dietary cholesterol. A significant (P less than .01) difference in body weight was present between the two lines, with low oxygen consuming (LOC) birds exhibiting heavier body weights than high oxygen consuming (HOC) birds. A significant interaction between line and energy intake (P less than .05) was present for hepatic cholesterol levels; LOC birds exhibited higher levels of hepatic cholesterol than HOC birds when both groups were fed at restricted levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Foods and techniques for managing obesity in companion animals.

Management of obesity should initially involve assessment of the pet to rule out other possible medical problems and provide an accurate dietary history. It is essential to obtain a good estimate of the existing caloric intake, including calories from table scraps, pet treats, or other sources. Assessing the owner's willingness to make a commitment to a major lifestyle change for their pet is also an important part of any successful weight-reduction program. In some instances, this motivation can be linked to a recent, expensive bill for orthopedic or other procedures performed on their pet. Once a candidate has entered a program, calculated restriction of energy while maintaining protein, vitamin, and mineral intake should be recommended. It may be surprising to find out that the calculated amounts of food may be more than the amount a pet is currently being fed. In these animals, it is imperative to use a high-protein, obesity-management diet and not a low-protein, "light," or senior type of diet containing high fiber. If possible, treats should be restricted altogether and begging actively discouraged. Any snacks should be placed in the pet's feeding bowl so that an association between eating and the bowel become established. Of equal importance is use of a realistic exercise program that owners will encourage their pet to follow. Various products for weight reduction are available. Use of these specially formulated products to restrict caloric intake, while maintaining essential nutrient intake and increasing energy expenditure by playing and other activities, are the hallmarks of successful weight loss programs.

Animal Feed↗

Serum leptin response to endogenous hyperinsulinemia in aging rats.

To determine if aging is associated with altered serum leptin response to diet-induced changes in endogenous hyperinsulinemia, male Fisher 344 (F344) rats at different age groups were studied while on regular rat chow and following 10 days of experimental diets consisting of 60% of the weight as fructose or glucose. The serum leptin concentration (ng/ml) gradually increased from basal levels of 2.5+/-0.1 at age of 4 months to 3.7+/-0.1, 6.9+/-0.9, 9. 4+/-0.3 and 8.9+/-1.1 at 6, 12, 18 and 24 months of age, respectively (P<0.001). Hyperinsulinemia associated with 60% fructose diet was associated with increased serum leptin levels in 4, 12, and 24 month old rats to 5.1+/-0.8, 6.7+/-1.2, and 8.6+/-1.1, respectively (P<0.001). Feeding 60% glucose diet also was associated with increased serum leptin levels in 4, 12 and 24 month old rats to 7.6+/-0.6, 7.2+/-0.7, and 9.1+/-1.1, respectively (P<0.001). Restricting dietary intake to 60% of the calories consumed by control rats for 10 days resulted in a decrease in serum leptin to 1.0+/-0.02 in 4 month old rats and 2.5+/-0.4 in 24 month old rats (P<0.01). It is concluded that aging in F344 rats is associated with increased serum leptin concentrations. However, diet-related hyperinsulinemic effect on leptin is blunted in aging rats although leptin response to caloric restriction is maintained. The inability of aging rats to mount hyperleptinemic response to dietary changes may contribute to the age-related increase in adiposity.

Aging↗

Modulation of leptin, insulin, and growth hormone in obese pony mares under chronic nutritional restriction and supplementation with ractopamine hydrochloride.

Horses fed beyond their nutritional requirement and that are physically inactive will develop obesity, which is often accompanied by insulin resistance and heightened risk of laminitis. The use of pharmacologic agents in combination with nutritional restriction may promote weight loss in obese horses unable to exercise because of laminitic pain. This study shows that reducing feed intake of brome grass hay to 75% of ad libitum intake in obese pony mares reduces body weight without induced exercise. Additional supplementation of ractopamine hydrochloride for 6 weeks resulted in a tendency for increased weight loss. Subsequent modulation of obesity-associated hormones, leptin and insulin, as a result of caloric restriction was observed.

Animals↗

Dietary patterns in anorexia nervosa.

This study characterized the dietary patterns of 96 patients with anorexia nervosa who were seen for diet history. The mean age of the patients was 16.6 yr, and mean loss from preillness weight was 28%. Twenty-five patients ate high-quality meals regularly but simply restricted calories. Eleven maintained a high-quality diet but ate at irregular intervals; of these, six had episodes of binge-eating and vomiting or fasting. Among patients whose diets were qualitatively poor, 19 consumed regular meals and 41 ate irregularly; 31 of the latter had episodes of binge-eating and vomiting or fasting. No typical profile of dietary manipulations by these patients was found. Beyond the generalization that there was caloric restriction that resulted in weight loss, there was great variability in the diet patterns.

Adolescent↗

Differential effect of total food withdrawal and dietary protein restriction on brain content of free histidine in the rat.

Total withdrawal of food from young rats for 72-120 h produced an increase in brain content of free histidine which was less pronounced than the effect of prolonged dietary protein deficiency. The data suggested that the elevated brain content of histidine in both fasting and protein deficiency was due partly to increased plasma level of the amino acid but mainly to diminished plasma concentrations of the neutral amino acids known to share the same transport system across the blood-brain barrier. The results also support the idea that total starvation, and most likely, prolonged caloric restriction, like protein malnutrition, elicit increased formation of histamine in brain since the key regulatory enzyme, L-histidine carboxylase (EC 4.1.1.22) functions at less than maximal efficiency under normal brain levels of histidine. These findings in the rat are probably relevant to the human in view of evidence that the Km of blood-brain barrier neutral amino acid transport in the latter is low and therefore similar to the situation in the rat.

Animals↗

Randomized crossover study of 40% vs. 55% carbohydrate weight loss strategies in women with previous gestational diabetes mellitus and non-diabetic women of 130-200% ideal body weight.

OBJECTIVE: The optimum diet composition for weight loss in obese women with or without previous gestational diabetes mellitus remains to be determined. Weight loss may be especially important for the latter group in terms of preventing future gestational as well as non-insulin dependent diabetes mellitus. We studied 40% vs. 55% carbohydrate calorically restricted diets to compare weight loss and metabolic response. METHODS: We performed a prospective, 12-week, blinded, randomized crossover study of 25 obese women; 13 of whom had previous gestational diabetes. Each woman was allocated to a treatment regimen for 6 weeks and then "crossed over" to the alternative regimen for an additional 6 weeks. Calories were provided in the form of nutritional supplement bars except for the evening meal that comprised 1/3 of the caloric needs. All subjects were seen and weighed weekly. Metabolic variables including glucose tolerance, glycated proteins, lipids, and percent body fat were measured at the beginning, crossover, and end of the study. RESULTS: Women with previous gestational diabetes mellitus were comparable to obese women without a history of previous gestational diabetes except that the former had higher maximum levels of glucose on a glucose tolerance test and higher fasting insulin levels consistent with greater insulin resistance. Weight loss was comparable for all groups during the first 6 weeks but attenuated in all groups during the second 6 weeks of the trial regardless of diabetes history or treatment group allocation. Women with or without a previous history of gestational diabetes had higher triglycerides while on a 55% carbohydrate diet than while on a 40% carbohydrate diet. CONCLUSIONS: A weight loss regimen consisting of 40% carbohydrate results in lower triglyceride levels than those achieved with a 55% carbohydrate content diet in obese women. Thus, the hypocaloric diet with the higher fat content produced the more favorable lipid profile in all obese women.

Adult↗

Delayed age-associated decrease in growth hormone pulsatile secretion and increased orexigenic peptide expression in the Lou C/JaLL rat.

Since modifications in the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis and/or caloric restriction are involved in the ageing process, GH secretory profiles, total IGF-1, ghrelin, and leptin plasma levels and expression of genes implicated in somatotrope axis and food intake regulation in hypothalamus and pituitary were compared in 3-, 12-, and 24-month-old male Lou C/Jall rats and their parent strain, the Wistar rats. The Lou C/Jall strain may appear as a healthy ageing model, since it does not become obese with age and maintains its caloric intake at 2 years of age. The GH pulsatile secretion decreased from 3 months in Wistar, but only after 12 months in Lou C/Jall rats. The IGF-1 levels were lower in Lou C/Jall rats and decreased more steeply with ageing as compared with Wistar rats. The total ghrelin levels were higher in young Lou C/Jall rats than in Wistar rats, but increased similarly with age in both strains. The leptin concentrations increased with ageing only in Wistar rats. By semiquantitative reverse-transcription polymerase chain reaction, pituitary GH secretagogue receptors and GH mRNA levels were more abundant in Lou C/Jall rats, and the latter decreased with ageing in Wistar rats only. Hypothalamic growth-hormone-releasing hormone and GH secretagogue receptor mRNA levels were similar in both strains and transiently increased only in middle-aged Wistar rats. Agouti-related peptide, neuropeptide Y, and orexin mRNA levels were more abundant in the Lou C/Jall rat hypothalamus, and the two former tended to further increase with age only in this strain. Conversely, the hypothalamic pro-opiomelanocortin mRNA levels were higher in old Wistar rats. In conclusion, ageing in Lou C/Jall rats is associated with a delayed decrease in pulsatile GH secretion in the presence of a lower IGF-1 tone and an increase in the expression of orexigenic neuropeptides in the hypothalamus.

Aging↗

Mid-life onset of dietary restriction extends life and prolongs cognitive functioning.

Fourteen-month-old C57BL/6 (NIA) mice were placed on a nutritionally complete diet providing 139.4 kcal/week. Over a 2-month period the food ration of experimental mice (AE) was reduced to 85 kcal/week, where it remained for the duration of the study. An aged control group (AC) continued with the higher calorie diet. At age 22 months, AC mice and half of the AE mice (AE22) were given a battery of behavioral tests. The remaining AE mice (AE25) were given the test battery at age 25 months. Also, a middle-aged control group (MC) was tested at age 13 months. Midlife onset caloric restriction (CR) increased longevity and preserved strength, coordination, and spontaneous alternation behavior, and altered responses to enclosed alleys. A spatial discrimination in the Morris water maze and a spatial delayed matching-to-sample water-escape task were insensitive to age and diet. The aged mice were adversely affected by testing.

Aging↗

Postprandial insulin response and mitochondrial oxidation in obese men nutritionally treated to lose weight.

Obesity, hyperglycemia, and insulin resistance have been associated to an oxidative mitochondrial dysfunction. The aim of this research was to evaluate the relation between carbohydrate metabolism and mitochondrial oxidation, as affected by the weight status and the weight loss induced by a calorie-restricted diet. Lean control men (BMI<25 kg/m2, n = 6) and obese men (BMI>30 kg/m2, n = 14), who were characterized as insulin resistant (n = 6) or insulin sensitive (n = 8) based on HOMA index values, participated in the trial. Plasma insulin levels and mitochondrial oxidation estimated by the 2-keto(1-13C)isocaproate breath test, were measured after ingestion of a test meal during 3 h. Obese subjects repeated the breath test protocol after a 10-week caloric restriction diet to lose weight. Postprandial insulin secretion tended to be marginally higher (P = 0.059) in both obese groups than in controls, while the rate of postprandial mitochondrial oxidation was markedly decreased (P = 0.019) in the obese subjects as compared with lean individuals. The nutritionally induced weight loss produced a rise in the postprandial oxidative process in volunteers initially considered as insulin resistant (P = 0.036), while no statistical differences in the insulin-sensitive obese (P = 0.241) were found. Interestingly, the percentage of oxidized tracer was inversely related to postprandial insulin secretion (r = -0.56; P = 0.001). In conclusion, these results support the hypothetized relation between carbohydrate metabolism and mitochondrial oxidation at a postprandial state in obese subjects, raising interest about mitochondria stimulation as a target in the therapy of obesity.

Adult↗

Epidemiologic data on the relationships of caloric intake, energy balance, and weight gain over the life span with longevity and morbidity.

Animal experiments have shown that calorically restricted (CR) animals weigh less and live longer than their ad libitum-fed peers. Are these observations applicable to human beings? This is an important question because the prevalence of obesity in America has increased markedly over recent years. We examine whether there are physiologic effects that occur with CR in humans that could plausibly explain the observed longevity of laboratory animals associated with CR. We also review epidemiologic data from observational and interventional studies on the relationships of caloric intake, energy balance, and weight gain with age-related diseases and longevity. Additionally, data on whether long-term, sustained maintenance of weight loss is feasible, as well as the degree of CR achieved in clinical trials, are summarized. Finally, we provide recommendations regarding further epidemiologic research that will help clarify unanswered questions in these areas.

Energy Intake↗

Studies on the formation of collagen. II. The influence of growth rate on neutral salt extracts of guinea pig dermis.

The total amount of neutral salt-extractible collagen in the skin of growing, suckling guinea pigs amounted to about 10 per cent of the total collagen of the dennis. This is roughly equivalent to a 1 to 2 day increment in dermal collagen incident to growth. Fourteen days of static weight maintained by limited caloric intake reduced the neutral salt-extractible collagen to very low levels. Following this period, 5 to 7 days of steady weight gain induced by ad lib. feeding was required to produce significant increases in this collagen fraction. Return to control levels occurred within 12 days of continuous growth. The amount of collagen extracted from the dermis of young guinea pigs with cold neutral salt solutions varied directly with growth rate (weight gain) and was greatly diminished after short periods of restricted caloric intake. Two days of fasting diminished the total extracted collagen by one-half. Three consecutive extractions with citrate buffer pH, 3.5, of the residues remaining after exhaustive saline extraction removed 40 per cent more collagen from the skins of actively growing animals than from those of animals fasted for 2 days. However, subsequent extraction of residues with dilute acetic acid equalized the total amount of collagen extracted at acid pH from the two groups. The viscosity of cold neutral extracts was unrelated to the concentrations of non-collagenous proteins and carbohydrates but varied directly with the collagen content.

Animals↗

Use of microarray biomarkers to identify longevity therapeutics.

A number of lines of evidence, including nonhuman primate and human studies, suggest that regulatory pathways similar to those invoked by caloric restriction (CR) may be involved in determining human longevity. Thus, pharmaceuticals capable of mimicking the molecular mechanisms of life- and health-span extension by CR (CR mimetics) may have application to human health. CR acts rapidly, even in late adulthood, to begin to extend life- and health-span in mice. We have linked these effects with rapid changes in the levels of specific gene transcripts in the liver and the heart. Our results are consistent with the rapid effects of caloric intake on the lifespan and/or biochemistry and physiology of Drosophila, rodents, rhesus macaques and humans. To test the hypothesis that existing pharmaceuticals can mimic the physiologic effects of CR, we evaluated the effectiveness of glucoregulatory drugs and putative cancer chemo-preventatives in reproducing the hepatic gene-expression profiles produced by long-term CR (LTCR). We found that 8 weeks of metformin treatment was superior to 8 weeks of CR at reproducing the specific changes in transcript levels produced by LTCR. Consistent with these results, metformin reduces cancer incidence in diabetic humans and ameliorates the onset and severity of metabolic syndrome. Metformin extends the mean and maximum lifespans of female transgenic HER-2/neu mice by 8% and 13.1% in comparison with control mice. Phenformin, a close chemical relative of metformin, extends lifespan and reduces tumor incidence in C3H mice. These results indicate that gene-expression biomarkers can be used to identify promising candidate CR mimetics.

Aging↗

Food-anticipatory rhythms under 24-hour schedules of limited access to single macronutrients.

Food-restricted rats anticipate a fixed daily mealtime by entrainment of a circadian timekeeping mechanism separate from that which generates daily light-entrainable activity rhythms. The entrainment pathways and rhythm-generating substrates for food-anticipatory rhythms are unknown. In this study, we attempted to define minimal food-related stimuli necessary or sufficient for food anticipation by employing schedules of restricted macronutrient availability, with or without free access to a complementary diet. Rats did not anticipate a daily meal of protein, carbohydrate, or fat, as measured by tilt-cage, running-wheel, or food-bin activity, when they had free access to other nutrients. However, rats did anticipate single-macronutrient meals when they were limited to only two, larger, complementary meals each day (protein-fat, protein-carbohydrate) providing a reduced total number of calories. Previous work has shown that caloric restriction per se is not a prerequisite for food anticipation. In combination with that study, the present results indicate that the size of a nutrient meal, in absolute terms or relative to total daily nutrient intake, is of pre-eminent importance in determining its value as a synchronizer of anticipatory rhythms. The results further suggest that physiological responses unique to the ingestion and absorption of any particular macronutrient are not necessary components of the entrainment pathway.

Animals↗