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Exercise is not an effective weight loss modality in women.

The excess caloric expenditure which results from physical activity should lead to weight loss if caloric expenditure at other times remains constant. Unfortunately, while there is good evidence for such an effect in men, there is little if any evidence for a similar effect in women. Weight loss with exercise does not readily occur in women unless accompanied by caloric restriction. Further, the role of exercise in maintaining resting metabolic rate while dieting has only marginal support. Potential reasons for the ineffectiveness of exercise in inducing weight loss in women include smaller body size and lower aerobic capacity, under-reporting of caloric intake, differences in body fat distribution and sensitivity to catecholamines, a different gonadal hormone milieu, and energy conservation resulting from evolutionary pressures. Nevertheless, regular exercise in women has many beneficial effects on lipids, glucose homeostasis and bone metabolism even if weight loss does not occur.

Adipose Tissue↗

Dietary restriction at old age lowers mitochondrial oxygen radical production and leak at complex I and oxidative DNA damage in rat brain.

Previous studies in mammalian models indicate that the rate of mitochondrial reactive oxygen species ROS production and the ensuing modification of mitochondrial DNA (mtDNA) link oxidative stress to aging rate. However, there is scarce information concerning this in relation to caloric restriction (CR) in the brain, an organ of maximum relevance for ageing. Furthermore, it has never been studied if CR started late in life can improve those oxidative stress-related parameters. In this investigation, rats were subjected during 1 year to 40% CR starting at 24 months of age. This protocol of CR significantly decreased the rate of mitochondrial H(2)O(2) production (by 24%) and oxidative damage to mtDNA (by 23%) in the brain below the level of both old and young ad libitum-fed animals. In agreement with the progressive character of aging, the rate of H(2)O(2) production of brain mitochondria stayed constant with age. Oxidative damage to nuclear DNA increased with age and this increase was fully reversed by CR to the level of the young controls. The decrease in ROS production induced by CR was localized at Complex I and occurred without changes in oxygen consumption. Instead, the efficiency of brain mitochondria to avoid electron leak to oxygen at Complex I was increased by CR. The mechanism involved in that increase in efficiency was related to the degree of electronic reduction of the Complex I generator. The results agree with the idea that CR decreases aging rate in part by lowering the rate of free radical generation of mitochondria in the brain.

Aging↗

Body dissatisfaction and dieting in young children.

OBJECTIVE: To develop a broader understanding of young children's knowledge and beliefs about dieting and body dissatisfaction. METHOD: Sixty-two third through sixth-grade boys and girls completed audiotaped interviews and questionnaires regarding eating behavior, attitudes toward dieting, and body dissatisfaction. RESULTS: Fifty percent of all children wanted to weigh less and 16% reported attempting weight loss. Children were well informed about dieting and were most likely to believe that dieting meant changing food choices and exercising as opposed to restricting intake. Their primary source of information was the family. Seventy-seven percent of children mentioned hearing about dieting from a family member, usually a parent. DISCUSSION: Young children are knowledgeable about dieting and the concept of dieting does not necessarily mean caloric restriction to them. These data suggest that the family can play a powerful role in countering the development of eating concerns and body dissatisfaction in children.

Adolescent↗

Influence of age, sex, and dietary restriction on intracellular free calcium responses of CD4+ lymphocytes in rhesus monkeys (Macaca mulatta).

The influence of aging and dietary restriction on increase in intracellular free calcium ([Ca2+]i) of CD4+ lymphocytes from Macaca mulatta was examined after stimulation with anti-CD3 mAb. We used a flow cytometric assay with the dye indo-1 and either direct or reciprocal immunofluorescent staining to identify CD4+ cells. After stimulation with anti-CD3 mAb, intracellular free calcium responses were reduced in CD4+ lymphocytes from old male and female ad libitum fed monkeys compared to young and adult male or female monkeys. Old female monkeys had significantly lower [Ca2+]i than did old male monkeys. The reduced responses were in part related to a decreased percentage of responding cells. Dietary restriction of males over a four-year period did not alter [Ca2+]i response compared to ad libitum fed male monkeys. Female monkeys of all ages (which were restricted only for four months) also had similar [Ca2+]i responses to ad libitum fed controls. Our data suggest that age-related changes in [Ca2+]i responses are similar between humans and M. mulatta, and that over these intervals, no effects of caloric restrictions can be detected.

Aging↗

DNA and DNases in normal and undernourished rat brain.

Earlier studies from our laboratory [Shrivastaw and Subba Rao, 1975; Subba Rao and Shrivastaw, 1976] have indicated a positive correlation between cell proliferation, as indicated by DNA synthesis, and the levels of DNases in developing chick brain. Since undernutrition is known to affect cell proliferation in developing brain, those studies are now extended to see the effect of early undernutrition on the levels of DNA and DNases along with RNA and protein in developing rat brain. Early nutritional deprivation resulted in lesser amounts of DNA, but the concentration of DNA per gram of brain did not alter. DNA, RNA, and protein values in brains of those rats undernourished from birth to 14 days but subsequently rehabilitated up to 130 days, exhibited complete recovery, while rehabilitation up to 50 days did not show full recovery in the case of DNA. Both the specific activity and total activity of acid and alkaline DNases showed significant reduction in 14-day-old undernourished brain. However, with continued nutritional restriction up to 24 days, the specific activity of these enzymes returned to normal, although the total activity was still in deficit. These results, coupled with those on DNA levels, indicate that a compensatory mechanism may come into play when developing brain is exposed to caloric restriction.

Animals↗

Expression and cDNA cloning of porcine peroxisome proliferator-activated receptor gamma (PPARgamma).

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the PPAR subfamily of nuclear hormone receptors. In rodents and humans, expression of PPARgamma is predominantly found in adipose tissue where it regulates adipocyte differentiation and the expression of multiple adipocyte genes. The primary aim of this work was to clone the porcine PPARgamma cDNA and examine the regulation of gene expression in porcine subcutaneous adipose tissue. The porcine PPARgamma gene encodes a 1.8-kb mRNA transcript and shares 99, 96 and 97% amino acid sequence identity to the human, mouse and cow PPARgamma molecules, respectively. Both isoforms of PPARgamma (gamma1 and gamma2) are highly expressed in porcine adipose tissue. The gamma2 isoform is expressed in low abundance in porcine spleen, whereas the gamma1 isoform is highly expressed in spleen and lung and at a low abundance in several other tissues. Western blot analysis confirmed a high level of PPARgamma protein expression in porcine adipose tissue compared to other tissues. Both caloric restriction and fasting significantly reduced PPARgamma2 but not gamma1 mRNA and PPARgamma protein abundance in subcutaneous adipose tissue compared to ad-libitum fed controls. We provide the first evidence that PPARgamma is abundantly expressed in porcine subcutaneous adipose tissue, and that expression is regulated by caloric intake. Thus, PPARgamma may play an important role in adipogenesis and hormone action in porcine adipocytes.

Adipose Tissue↗

Seizure resistance is dependent upon age and calorie restriction in rats fed a ketogenic diet.

The present study was designed to evaluate the effects of age on the efficacy of the ketogenic diet in suppressing seizures evoked by tail-vein infusion of pentylenetetrazole (PTZ). Male rats of various ages were divided into three groups and fed one of three diets: (1) a calorie-restricted ketogenic diet, (2) a calorie-restricted normal (rodent chow) diet, or (3) a normal diet, ad libitum. After animals had been on experimental or control diets for more than 20 days, seizure threshold and blood levels of beta-hydroxybutyrate (beta-OHB) were determined. Animals fed a ketogenic diet exhibited significant elevations in levels of beta-OHB and seizure resistance compared to animals fed either a calorie-restricted normal diet or a normal diet, ad libitum. The levels of beta-OHB and seizure resistance were greatest for young pups. A surprising finding was that young animals fed a calorie-restricted rodent chow diet exhibited a significantly increased resistance to seizures compared to those fed the same diet, ad libitum. Results presented here demonstrate that the ketogenic diet produces the highest levels of ketonemia and seizure threshold in young animals. Collectively, these data suggest that age and caloric restriction are important considerations for implementing the ketogenic diet.

3-Hydroxybutyric Acid↗

Aerobic exercise maintains regional bone mineral density during weight loss in postmenopausal women.

This study examines the effects of weight loss by caloric restriction (WL) and aerobic exercise plus weight loss (AEx+WL) on total and regional bone mineral density (BMD) in older women. Healthy, postmenopausal women [age 63 +/- 1 (SE) yr] not on hormone-replacement therapy underwent 6 mo of WL (n = 15) consisting of dietary counseling one time per week with a caloric deficit (250-350 kcal/day) or AEx+WL (n = 15) consisting of treadmill exercise three times per week in addition to the weight loss. Maximal aerobic capacity increased only in the AEx+WL group (P < 0. 001). Body weight, percent fat, and fat mass decreased similarly in both groups (P < 0.005), with no changes in fat-free mass. Total body BMD (by dual-energy X-ray absorptiometry) decreased in both groups (P < 0.05). Femoral neck, Ward's triangle, and greater trochanter BMD decreased in the WL group (P </= 0.05) but were not significantly different after AEx+WL. L2-L4 BMD did not significantly change in either group. Thus WL and AEx+WL both result in losses of total body BMD; however, AEx+WL appears to prevent the loss in regional BMD seen with WL alone in healthy, older women. This suggests that the addition of exercise to weight-loss programs may reduce the risk for bone loss.

Aged↗

[Ten questions on the treatment of obesity: from dieting to surgery].

Advantages and risk of weight reduction achieved by combining diets or unbalanced diets with restriction of carbohydrates or fat are discussed. Nutriments differ according to their density, their flavour, their satiating, and their thermogenic effect. Food is also a source of pleasure and a remedy to frustration. One of the problems of dieting is that most patients regain the weight they have lost due to a hypometabolism secondary to caloric restriction. Only physical exercise together with behavior therapy are able to slow down this weight regain. The indication of drug treatment with orlistat, sibutramine and fluoxetin and the indication to bariatric surgery are presented. The importance of the prevention of obesity by nutrition teaching in schools as well as the necessity of a long term treatment as in type II diabetes are underlined.

Appetite Depressants↗

Obesity, metabolism, and the sympathetic nervous system.

The association of hypertension and obesity is poorly understood. Studies conducted in our laboratory over the last decade, in conjunction with recent clinical and epidemiological observations, suggest that hypertension in the obese is derived from a fundamental relationship between dietary intake and sympathetic nervous system (SNS) activity. The application of kinetic techniques to the measurement of norepinephrine (NE) turnover rate in sympathetically innervated tissues of laboratory rodents has defined a relationship between the SNS and dietary intake. Fasting or caloric restriction suppresses sympathetic activity in a variety of organs of the rat, including heart and interscapular brown adipose tissue. Overfeeding a mixed, palatable, "cafeteria" diet stimulates sympathetic activity in these same tissues. The stimulatory effect of mixed diets is due to the carbohydrate and fat content, because these two latter nutrients stimulate sympathetic activity even when total caloric intake is not increased. Insulin-mediated glucose metabolism within central neurons associated with the ventromedial hypothalamus (VMH) plays an important role in the relationship between dietary intake and SNS activity as indicated by the following observations: (1) Hypoglycemia (noninsulin-mediated) is associated with suppression of the SNS (despite concomitant adrenal medullary stimulation); (2) 2-deoxyglucose, an intracellular inhibitor of glucose metabolism, decreases sympathetic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Eating↗

Obesity treatment: broadening our perspective.

OBJECTIVE: To selectively review the dietary literature to broaden perspectives on energy restriction as the primary determinant of successful obesity treatment. METHODS: Forty-five articles describing novel dietary behaviors and nutrient intakes that may impact obesity treatment are examined. RESULTS: Two areas of promising research were identified: (a) Dietary behaviors and patterns--eating frequency, meal timing, specific dietary pattern and (b) Nutritional factors--fat, fiber, glycemic load, carbohydrate. CONCLUSIONS: Caloric restriction leads to weight loss. However, promotion of dietary behaviors that focus primarily on cutting calories needs evaluation. There may be many dietary behaviors and patterns that promote weight loss and maintenance, making it essential to consider new nutritional approaches for obesity treatment.

Body Mass Index↗

Calorie restriction inhibits the age-related dysregulation of the cytokines TNF-alpha and IL-6 in C3B10RF1 mice.

TNF-alpha and IL-6 are generally increased in the sera of aged humans and mice. The dysregulation of these cytokines may be critical in autoreactivity and immune dysfunction. In earlier studies we demonstrated that production of TNF-alpha and IL-6 following in vitro stimulation of peritoneal macrophages by LPS was reduced in old compared to young mice, and that dietary caloric restriction (CR) had no effect on the induction of TNF-alpha in this system. In the present study we examined the effects of age and calorie restriction on the constitutive production of both TNF-alpha and IL-6. Serum levels of both cytokines were significantly higher in old versus young mice. However, in old mice subjected to long term CR the serum levels were comparable to those of young mice. The potential involvement of normalization of TNF-alpha and IL-6 levels in the life extension effect of CR are discussed.

Aging↗

Mechanisms of cancer chemoprevention in hepatic carcinogenesis: modulation of focal lesion growth in mice.

Studies in our laboratory have concentrated on further understanding the mechanism by which chemicals induce cancer and the means to prevent or retard this process. Recent investigations have revolved around the role of oxidative stress and oxidative damage in the induction of cancer by nongenotoxic carcinogens. Hepatocarcinogenic compounds including selective chlorinated hydrocarbons appeared to induce oxidative stress in the liver. This oxidative stress and oxidative damage in turn may be responsible for the tumor-promoting activity of these compounds. Reduction of oxidative damage by antioxidants, or dietary-restriction, results in an ablation of the induction of selective cell growth by these agents. The oxidative stress induced by nongenotoxic agents may influence cell proliferation and/or apoptosis in the preneoplastic cells. Our studies with nongenotoxic hepatic carcinogens showed a dose-dependent increase in oxidative stress and an increase in hepatic focal lesion growth. Antioxidant dietary supplementation or caloric restriction prevented the lesion growth. This appeared to be through an increase in apoptosis in the hepatic lesions.

Animals↗

Effect of somatotropin and feed restriction on body composition and adipose metabolism in obese Zucker rats.

The objective of the present study was to determine whether exogenous somatotropin (STH) administration in conjunction with feed restriction could alter the composition of gain in the obese rat. Five-week-old female lean and obese Zucker rats were assigned to the following treatments for 6 wk: ad libitum fed (AL), restricted (approximately 75% of AL lean), and restricted with STH (2 mg STH/day). Growth rate was decreased in restricted groups and was normalized to that of the AL lean group in restricted rats treated with STH. In lean rats, restriction decreased protein accretion. Restriction plus STH treatment decreased lipid accretion but increased protein accretion and body weight gain compared with the AL lean group. As expected, feed restriction reduced body size in obese rats, but carcass lipid was maintained at 44%, a level similar to that of the AL obese rats. Lipid accretion rate was decreased with restriction in obese rats and was further reduced, to a level similar to that of the lean group, in the obese rats that were restricted and treated with STH. Protein accretion was decreased in the restricted obese group but was normalized in those treated with STH to a level similar to that in the AL lean group. Basal rates of lipolysis in isolated adipocytes were not affected by STH. However, STH treatment normalized the responsiveness of cells from the obese rats to stimulation of lipolysis by isoproterenol. The results demonstrate that a combination of caloric restriction and STH was effective in normalizing body weight and composition of gain in the obese Zucker rat.

Adipose Tissue↗

Impaired secretion of growth hormone in experimental uremia: relevance of caloric deficiency.

To evaluate the impact of uremia and associated caloric restriction on physiologically pulsatile growth hormone (GH) release, we used deconvolution analysis of spontaneous plasma GH profiles in 5/6-nephrectomized male rats (NX, N = 9). Three different normal renal function sham-operated groups were used: rats fed a normal diet ad libitum (SAL, N = 9); NX pair-fed rats (SPF, N = 6); NX rats pair-fed for protein ingestion but calorically supplemented up to the energy intake of SAL (SPF+, N = 8). Severe renal failure was confirmed by much higher (P < 0.001) BUN in NX than sham groups. NX rats were growth retarded as shown by reduced (P < 0.01) weight and length gains as compared with sham animals. Deconvolution analysis (mean +/- SEM) of plasma samples obtained every 10 minutes over 6 hours, and 14 to 16 days after second stage nephrectomy showed that NX rats had a longer GH t(1/2) (17.0 +/- 1.8 vs. 11.6 +/- 0.8 min), less GH mass secreted per burst (48 +/- 15 vs. 95 +/- 16 ng/ml/pulse), lower secretory pulse amplitude (1.9 +/- 0.5 vs. 5.8 +/- 0.9 ng/ml/min), and a reduced total GH secretion (240 +/- 69 vs. 400 +/- 56 ng/ml/6 hr) than SAL rats. Corresponding data were not significantly different between NX and SPF, or between SAL and SPF+ groups. In summary, stunted rats with chronic renal failure exhibit a prolonged GH t(1/2) and suppression of GH secretory pattern burst mass. Control data from rats with normal renal function suggest that the amplitude-specific depression of GH secretion may be attributed, at least in part, to chronic renal failure-associated calorie deficiency.

Animals↗

Food restriction retards age-related biochemical changes in rat small intestine.

Previous studies have demonstrated that the specific activities of several proximal small intestinal mucosal enzymes fall in the aging rat. This reduction was due to a delay in the full expression of activity of these enzymes during epithelial cell transit from the crypt onto the intestinal villus. We now show in the ad libitum fed Fischer 344 rat that jejunal sucrase, maltase, and alkaline phosphatase specific activities do not fall gradually throughout the life span, but are reduced during senescence. Caloric restriction to 60% of ad libitum intake (DR) abolishes or delays this fall in enzyme activity. Jejunal mucosal immunoprecipitable sucrase-isomaltase (S-I) content also falls with age, but sucrase specific activity per molecule of S-I is less in the older ad libitum fed (approximately 45) than in the DR rats (approximately 60). Jejunal lactase activity falls gradually throughout the life span of ad libitum and DR rats, but lactase activity consistently was higher in DR animals. These observations indicate that DR alters the age-related changes in the activity of several enzymes in the rapidly replicating gut mucosa.

Aging↗

Deviations in brain development of F2 generation on caloric undernutrition and scope of their prevention by rehabilitation: alterations in dendritic spine production and pruning of pyramidal neurons of lower laminae of motor cortex and visual cortex.

This is a report of comparison of developmental changes of spine densities on the different categories of dendrites of neocortical pyramidal neurons (V and VI layers of motor and visual areas) of Wistar rat, during 11-150 days of age, under conditions of normal nutrition and under chronic caloric but not protein deprivation. The studied animals were of F2 generation born to parents undernourished to a degree that their weights were only 40-50% of normal control. At such a level they would be active, reproduce, and not morbid. Similar level of undernutrition also continued in the F2 group studied. A group of undernourished animals was also, for rehabilitation, put on normal diet from 21 days of age. Visual and motor cortical area pieces were impregnated by Stensaas' rapid Golgi method. Spines were counted on successive 20-micron segments (I-IV) of both apical and basal dendritic main shafts as well as primary and secondary branches. The spine count per segment (density) in the normal population reached exuberant values by 26-50 days of age and later underwent a progressive decline or pruning by 30-50% or more by 150 days of age. The degrees of exuberance and pruning varied in different categories of dendrites, generally being more conspicuous in motor than visual cortex, and more in basal than apical dendrites. Under the conditions of chronic caloric restriction, the phenomenon of exuberance was retarded and pruning was not observed. On the contrary, there was a progressive increase in the spine densities on both basal and apical dendrites, in motor and visual cortex. By 150 days of age, the spine densities were not only greater than the final counts for respective segments in the normal animal, but even greater than the exuberant counts. Postweaning caloric rehabilitation had only a modest impact against this deviation. Preliminary data (intersections) of dendritic branching also indicated a similar pattern of changes (lag followed by increase), but of a lesser degree. These alterations in neuronal development are interpreted as biological adaptations evoked in shaping the homeostasis of the organism's brain and behaviour by factors of nurture.

Aging↗

Caloric intake, body weight, and cancer: a review.

The literature is reviewed for evidence concerning the relation between caloric intake, body weight, and cancer. Convincing experimental data regarding caloric intake and benign and malignant tumor incidence have been available since the 1940s and demonstrate that caloric restriction significantly reduces tumor incidence for a variety of tumor types in several animal models. Some epidemiological investigations provide evidence for a positive calorie-cancer association in humans, although it is difficult (in these studies) to separate the effects of calories per se from those of dietary fat. A larger number of investigations have evaluated body weight alone, and high relative body weight or high caloric intake has been associated with increased risk of cancer of the breast, colon, rectum, prostate, endometrium, kidney, cervix, ovary, thyroid, and gallbladder. In contrast, lung, bladder, and stomach cancers appear to be inversely associated with body weight, and some prospective studies of men demonstrate greater total cancer mortality among lean individuals. However, in their analyses, few of these latter investigations considered the effects of cigarette smoking, antecedent illness, or competing causes of death. While the relations between caloric intake, other dietary macronutrients (e.g., fat), and body weight are complex and require further investigation, a complete review of the data suggests that reducing caloric intake and relative body weight may lead to a considerable decrease in cancer risk in humans.

Animals↗