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Smokers report weight and appetite control as motivators to smoking continuance. These concerns are particularly salient for smokers who use cigarettes to suppress appetite and manage weight. Dieting may influence weight, shape, and appetite-related smoking motivation; however, this has not yet been examined. This study tested associations between five diet types and smoking motivation to control weight, shape, and appetite among adult daily cigarette smokers (N = 550). A multivariate analysis was used to test the incremental association between diet types and Smoking-Related Weight and Eating Episodes Test (SWEET) subscales, adjusting for age, body mass index, sex, and cigarette dependence. Smokers who diet (n = 83, 15.1%) reported higher scores on all SWEET subscales compared to smokers not on a diet. Low-calorie dieting was associated with greater smoking motivation to cope with body dissatisfaction, and low-sugar dieting was associated with greater motivation for smoking to prevent withdrawal-related appetite increases. Treatment implications for smoking cessation are discussed., Author(s): Kathryn A. Coniglio [sup.1] , Rachel Rosen [sup.1] , Emily K. Burr [sup.1] , Samantha G. Farris [sup.1] Author Affiliations: (1) grid.430387.b, 0000 0004 1936 8796, Department of Psychology, [...]

BACKGROUND. Hepatic de novo lipogenesis (DNL) is elevated in nonalcoholic fatty liver disease (NAFLD). Improvements in hepatic fat by dietary sugar reduction may be mediated by reduced DNL, but data are limited, especially in children. We examined the effects of 8 weeks of dietary sugar restriction on hepatic DNL in adolescents with NAFLD and correlations between DNL and other metabolic outcomes. METHODS. Adolescent boys with NAFLD (n = 29) participated in an 8-week, randomized controlled trial comparing a diet low in free sugars versus their usual diet. Hepatic DNL was measured as percentage contribution to plasma triglyceride palmitate using a 7-day metabolic labeling protocol with heavy water. Hepatic fat was measured by magnetic resonance imaging-proton density fat fraction. RESULTS. Hepatic DNL was significantly decreased in the treatment group (from 34.6% to 24.1%) versus the control group (33.9% to 34.6%) (adjusted week 8 mean difference: -10.6% [95% CI: -19.1%, -2.0%]), which was paralleled by greater decreases in hepatic fat (25.5% to 17.9% vs. 19.5% to 18.8%) and fasting insulin (44.3 to 34.7 vs. 35.5 to 37.0 [micro]IU/ mL). Percentage change in DNL during the intervention correlated significantly with changes in free-sugar intake (r = 0.48, P = 0.011), insulin (r = 0.40, P = 0.047), and alanine aminotransferase (ALT) (r = 0.39, P = 0.049), but not hepatic fat (r = 0.13, P = 0.532). CONCLUSION. Our results suggest that dietary sugar restriction reduces hepatic DNL and fasting insulin, in addition to reductions in hepatic fat and ALT, among adolescents with NAFLD. These results are consistent with the hypothesis that hepatic DNL is a critical metabolic abnormality linking dietary sugar and NAFLD. TRIAL REGISTRY. ClinicalTrials.gov NCT02513121. FUNDING. The Nutrition Science Initiative (made possible by gifts from the Laura and John Arnold Foundation, Ambrose Monell Foundation, and individual donors), the UCSD Altman Clinical and Translational Research Institute, the NIH, Children's Healthcare of Atlanta and Emory University's Children's Clinical and Translational Discovery Core, Children's Healthcare of Atlanta and Emory University Pediatric Biostatistical Core, the Georgia Clinical and Translational Science Alliance, and the NIH National Institute of Diabetes, Digestive, and Kidney Disease. Related Commentary: https://doi.org/10.1172/JCI154645, Introduction The prevalence of pediatric nonalcoholic fatty liver disease (NAFLD), defined by hepatic fat accumulation in the absence of excess alcohol intake, has increased considerably over recent decades (1, 2). [...]

Background/Objectives: Normal-weight women frequently restrict their caloric intake and exercise, but little is known about the effects on body weight, body composition and metabolic adaptations in this population. Subjects/Methods: We conducted a secondary analysis of data from a randomized controlled trial in sedentary normal-weight women. Women were assigned to a severe energy deficit (SEV: -1062[plus or minus]80 kcal per day; n=9), a moderate energy deficit (MOD: -633[plus or minus]71 kcal per day; n=7) or energy balance (BAL; n=9) while exercising five times per week for 3 months. Outcome variables included changes in body weight, body composition, resting metabolic rate (RMR) and metabolic hormones associated with energy conservation. Results: Weight loss occurred in SEV (-3.7[plus or minus]0.9 kg, P0.33). RMR decreased by -6[plus or minus]2% in MOD (P=0.020). In SEV, RMR did not change on a group level (P=0.66), but participants whose RMR declined lost more weight (P=0.020) and had a higher baseline RMR (P=0.026) than those whose RMR did not decrease. Characteristic changes in leptin (P=0.003), tri-iodothyronine (P=0.013), insulin-like growth factor-1 (P=0.016) and ghrelin (P=0.049) occurred only in SEV. The energy deficit and adaptive changes in RMR explained 54% of the observed weight loss. Conclusions: In normal-weight women, caloric restriction and exercise resulted in less-than-predicted weight loss. In contrast to previous literature, weight loss consisted almost exclusively of fat mass, whereas fat-free mass was preserved., Author(s): K Koehler [sup.1] [sup.2] , M J De Souza [sup.1] , N I Williams [sup.1] Author Affiliations: (1) Department of Kinesiology, Pennsylvania State University, University Park, USA (2) Department [...]

Background/Objectives: Although energy restriction contributes to weight loss, it may also reduce energy expenditure, limiting the success of weight loss in the long term. Studies have described how genetics contributes to the development of obesity, and uncoupling proteins 1 and 2 (UCP1 and UCP2) and beta-3-adrenoceptor (ADRB3) have been implicated in the metabolic pathways that culminate in this condition. This study aimed to evaluate how the UCP1, UCP2 and ADRB3 genes influence weight loss in severely obese women submitted to hypocaloric dietary intervention. Subjects/Methods: This longitudinal study included 21 women divided into two groups: Group 1 (Dietary intervention (G1)) consisted of 11 individuals with severe obesity (body mass index (BMI) [greater-than or slanted equal to]40 kg/m.sup.2), selected for dietary intervention and Group 2 (Control (G2)) consisted of 10 normal-weight women (BMI between 18.5 and 24.9 kg/m.sup.2). Evaluation included weight (kg), height (m), waist circumference (cm), body composition, resting metabolic rate (RMR, kcal) and abdominal subcutaneous adipose tissue collection. The dietary intervention required that G1 patients remained hospitalized in the university hospital for 6 weeks receiving a hypocaloric diet (1200 kcal per day). The statistical analyses included t-test for paired samples, Spearman correlation and multivariate linear regressions, with the level of significance set at P Results: Weight (155.0[plus or minus]31.4-146.5[plus or minus]27.8 kg), BMI (58.5[plus or minus]10.5-55.3[plus or minus]9.2 kg/m.sup.2), fat-free mass (65.4[plus or minus]8.6-63.1[plus or minus]7.1 kg), fat mass (89.5[plus or minus]23.0-83.4[plus or minus]21.0 kg) and RMR (2511.6[plus or minus]386.1-2324.0[plus or minus]416.4 kcal per day) decreased significantly after dietary intervention. Multiple regression analyses showed that UCP2 expression contributed to weight loss after dietary intervention (P=0.05). Conclusions: UCP2 expression is associated with weight loss after hypocaloric diet intervention., Author(s): C Cortes-Oliveira [sup.1] , C F Nicoletti [sup.1] , M A de Souza Pinhel [sup.1] , B A P de Oliveira [sup.1] , D C G Quinhoneiro [sup.1] , [...]

To better understand the contribution of the fat mass to the effects of long-term caloric restriction in humans, we compared adipokine profile and insulin sensitivity in long-term calorically restricted formerly obese women (CRW) subjected to different interventions, bariatric surgery, or reducing diet, with age- and BMI-matched obese (OW) and normal-weight women (NW) eating ad libitum. Our key findings are that despite a considerably stronger weight loss induced by bariatric surgery, both long-term caloric restriction interventions improved insulin sensitivity to the same degree and led to significantly lower retinol-binding protein-4 and interleukin-6 serum levels than in OW, suggesting that lowering of these two adipokines contributes to the improved insulin sensitivity. Moreover, serum leptin was considerably lower in CRW than in OW as well as in NW, suggesting that CRW develop hypoleptinemia. Key Words: Aging--Adipokine--Bariatric surgery--Caloric restriction--Insulin sensitivity--Obesity doi: 10.1093/gerona/glq107

The societal impact of obesity, diabetes, and other metabolic disorders continues to rise despite increasing evidence of their negative long-term consequences on health span, longevity, and aging. Unfortunately, dietary management and exercise frequently fail as remedies, underscoring the need for the development of alternative interventions to successfully treat metabolic disorders and enhance life span and health span. Using calorie restriction (CR)--which is well known to improve both health and longevity in controlled studies--as their benchmark, gerontologists are coming closer to identifying dietary and pharmacological therapies that may be applicable to aging humans. This review covers some of the more promising interventions targeted to affect pathways implicated in the aging process as well as variations on classical CR that may be better suited to human adaptation. Key Words: Aging intervention--Health span--Life span--Metformin--Resveratrol. doi: 10.1093/gerona/glq042

Objectives. We assessed whether labeling restaurant menus with information on the nutrient content of menu items would cause customers to alter their ordering patterns. Methods. Six full-service restaurants in Pierce County, Washington, added nutrition information to their menus, and they provided data on entree sales for 30 days before and 30 days after the information was added. We assessed the prelabeling versus postlabeling difference in nutrient content of entrees sold, and we surveyed restaurant patrons about whether they noticed the nutrition information and used it in their ordering. Results. The average postlabeling entree sold contained about 15 fewer calories, 1.5 fewer grams of fat, and 45 fewer milligrams of sodium than did the average entree sold before labeling. Seventy-one percent of patrons reported noticing the nutrition information; 20.4% reported ordering an entree lower in calories as a result, and 16.5% reported ordering an entree lower in fat as a result. Conclusions. The concentration of calorie reduction among 20.4% of patrons means that each calorie-reducing patron ordered about 75 fewer calories than they did before labeling. Thus, providing nutrition information on restaurant menus may encourage a subset of restaurant patrons to significantly alter their food choices. (Am J Public Health. 2010;100:1035-1039. doi: 10.2105/AJPH.2009.174839)

Calorie restriction (CR) has been known for more than 70 years to extend life span and delay disease in rodent models. Metformin administration in rodent disease models has been shown to delay cancer incidence and progression, reduce cardiovascular disease and extend life span. To more directly test the potential of metformin supplementation (300 mg/ kg/day) as a CR mimetic, life-span studies were performed in Fischer-344 rats and compared with ad libitum feeding and CR (30%). The CR group had significantly reduced food intake and body weight throughout the study. Body weight was significantly reduced in the metformin group compared with control during the middle of the study, despite similar weekly food intake. Although CR significantly extended early life span (25th quantile), metformin supplementation did not significantly increase life span at any quantile (25th, 50th, 75th, or 90th), overall or maximum life span (p > .05) compared with control. Key Words: Calorie restriction--Metformin--Mimetic--Life span--Aging. doi: 10.1093/gerona/glq033

When the food intake of organisms such as yeast and rodents is reduced (dietary restriction), they live longer than organisms fed a normal diet. A similar effect is seen when the activity of nutrient-sensing pathways is reduced by mutations or chemical inhibitors. In rodents, both dietary restriction and decreased nutrient-sensing pathway activity can lower the incidence of age-related loss of function and disease, including tumors and neurodegeneration. Dietary restriction also increases life span and protects against diabetes, cancer, and cardiovascular disease in rhesus monkeys, and in humans it causes changes that protect against these age-related pathologies. Tumors and diabetes are also uncommon in humans with mutations in the growth hormone receptor, and natural genetic variants in nutrient-sensing pathways are associated with increased human life span. Dietary restriction and reduced activity of nutrient-sensing pathways may thus slow aging by similar mechanisms, which have been conserved during evolution. We discuss these findings and their potential application to prevention of age-related disease and promotion of healthy aging in humans, and the challenge of possible negative side effects. 10.1126/science.1172539

Objective: To investigate if dietary energy density is associated with measures of dietary quality (food group, micronutrient and macronutrient intakes) in children and adolescents. Subjects/Methods: In all, 551 children (mean age 9.6 years, 52% girls) and 569 adolescents (15.5 years, 55% girls), sampled from schools in Sweden, completed a single 24-h dietary recall. Dietary energy density (kJ/g) was calculated as the energy from all food consumed divided by the weight of all food consumed. Beverages were excluded from the calculation. Food and micronutrient intakes were adjusted for energy intake. A one-way analysis of variance (ANOVA) was used to test for differences in food group and nutrient intakes across age- and gender-specific tertiles of energy density. Discriminant analysis was used to confirm the groupings formed by tertiles. Results: Subjects with low-energy-density diets were significantly more likely to consume fruits, vegetables, pasta, rice, potatoes and cereals and less likely to consume sweetened drinks, sweets and chocolate. After energy adjustment, their intakes of many foods recommended in the Swedish food-based dietary guidelines were higher and intakes of nutrient-poor foods were lower. The macronutrient energy profile (% energy) of low-energy-density diets was closest to the recommended level. Low-energy-density diets contained greater amounts of most micronutrients. Discriminant analysis confirmed the existence of heterogeneous dietary patterns and the likelihood of correct classification by energy density in 65% of cases. Conclusions: Lower dietary energy density is associated with better dietary quality in children and adolescents. Energy density has advantages over other whole diet analysis methods and may be suitable as a simple proxy of diet quality. European Journal of Clinical Nutrition (2010) 64, 356-363; doi: 10.1038/ejcn.2009.160; published online 13 January 2010 Keywords: 24-h recall; dietary patterns; epidemiology; foods; nutrients, Introduction No simple, well-accepted criteria exist that allow diets to be classified as healthy or unhealthy. Attempts to assess overall diet quality have often relied on scores or indexes (Kant, [...]

Am J Physiol Endocrinol Metab 298: E108-E116, 2010. First published November 3, 2009; zdoi: 10.1152/ajpendo.00524.2009.--Calorie restriction (CR) increases longevity and retards the development of many chronic diseases, but the underlying metabolic signals are poorly understood. Increased fatty acid (FA) oxidation and reduced FA synthesis have been hypothesized to be important metabolic adaptations to CR. However, at metabolic steady state, FA oxidation must match FA intake plus synthesis; moreover, FA intake is low, not high, during CR. Therefore, it is not clear how FA dynamics are altered during CR. Accordingly, we measured food intake patterns, whole body fuel selection, endogenous FA synthesis, and gene expression in mice on CR. Within 2 days of CR being started, a shift to a cyclic, diurnal pattern of whole body FA metabolism occurred, with an initial phase of elevated endogenous FA synthesis [respiratory exchange ratio (RER) > 1.10, lasting 4-6 h after food provision], followed by a prolonged phase of FA oxidation (RER = 0.70, lasting 18-20 h). CR mice oxidized four times as much fat per day as ad libitum (AL)-fed controls (367 [+ or -] 19 vs. 97 [+ or -] 14 mg/day, P < O.001) despite reduced energy intake from fat. This increase in FA oxidation was balanced by a threefold increase in adipose tissue FA synthesis compared with AL. Expression of FA synthase and acetyl-CoA carboxylase mRNA were increased in adipose and fiver in a time-dependent manner. We conclude that CR induces a surprising metabolic pattern characterized by periods of elevated FA synthesis alternating with periods of FA oxidation disproportionate to dietary FA intake. This pattern may have implications for oxidative damage and disease risk. fat synthesis; lipogenesis; palmitoleate; heavy water

Abstract Female obese volunteers participating in a double blind study, and submitted to the administration of an oral presentation of hCG (Human Choriogonadotropin) plus a VLCD (Very Low Calorie Diet), [...]

Dietary restriction (DR) is a widely conserved intervention leading to lifespan extension. Despite considerable effort, the mechanisms underlying DR remain poorly understood. In particular, it remains unclear whether DR prolongs life through conserved mechanisms in different species. Here, we show that, in the most common experimental conditions, lifespan extension by DR is abolished by providing Drosophila with ad libitum water, without altering food intake, indicating that DR, as conventionally studied in flies, is fundamentally different from the phenomenon studied in mammals. We characterize an alternative dietary paradigm that elicits robust lifespan extension irrespective of water availability, and thus likely represents a more relevant model for mammalian DR. Our results support the view that protein:carbohydrate ratio is the main dietary determinant of fly lifespan. These findings have broad implications for the study of Iifespan and nutrition. aging | caloric restriction | dehydration | longevity | nutrition www.pnas.org/cgi/doi/10.1073/pnas.0908016106

Calorie restriction (CR) enhances immune response and prolongs life span in animals. However, information on the applicability of these results to humans is limited. T-cell function declines with age. We examined effects of CR on T-cell function in humans. Forty-six overweight, nonobese participants aged 20-42 years were randomly assigned to 30% or 10% CR group for 6 months. Delayed-type hypersensitivity (DTH), T-cell proliferation (TP), and prostaglandin [E.sub.2] ([PGE.sub.2]) productions were determined before and after CR. DTH and TP to T-cell mitogens were increased in both groups over baseline (p [less than or equal to] .019). However, number of positive responses to DTH antigens (p = .016) and TP to anti-CD3 reached statistical significance only alter 30% CR (p = .001). Lipopolysaccharide-stimulated [PGE.sub.2] was reduced in both groups but reached statistical significance after 30% CR (p [less than or equal to] .029). These results, for the first time, show that 6-month CR in humans improves T-cell function. Key Words: Calorie restriction--T cell--Immune response--Aging--Obesity. doi: 10.1093/gerona/glp101

Repetitive cycles of palatable food access and chronic calorie restriction alter feeding behaviors and forebrain neural systems. The purpose of this study was to determine the behavioral, endocrine, and meal-related hindbrain neural activation in adult male Sprague-Dawley rats exposed to a binge-access feeding schedule. The binge-access schedule consisted of repeated twice-per-week episodes of acute calorie restriction (to one-third of the previous day's intake) followed by 2 h of concurrent access to high-calorie palatable food (sweetened fat: 90% vegetable shortening-10% sucrose) and chow. The binge-access rats consumed more calories during the 'binge' period than rats with continuous access to sweetened tat (continuous-access group) or subjected to repeated acute calorie restriction only (chow-restricted group). The binge-access group also exhibited a ~25% increase in sweetened fat intake from week 1 to week 6. Persistence of the binge phenotype in the binge-access animals was demonstrated 2 wk, but not 4 wk, after ad libitum chow. The binge-access and chow-restricted groups maintained a similar normal body composition and hormonal profiles, whereas the continuous-access animals developed an obese phenotype. Terminal ghrelin levels were significantly higher in the bingeaccess group than in the continuous-access group. Consumption of a standardized meal resulted in more c-Fos-positive cells along the anterior-posterior nucleus of the solitary tract regions in the bingeaccess group than in naive controls. These results suggest that repeated cycles of acute calorie restriction followed by palatable food produce physiological alterations that may facilitate overconsumption of a highly palatable food during limited-access periods. bulimia nervosa; binge eating; nucleus of the solitary tract; area postrema

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jada.2009.05.003 Byline: Emily A. Furlow, James W. Anderson Abstract: Accurate information about weight loss is not available for most commercial weight-loss programs. Our objective was to obtain accurate assessments of weight outcomes, behavioral data, and side effects for an intensive behavioral weight-loss program using low-energy diets. Weights, behavioral data, and side effects for 173 consecutive patients were assessed. Treatment options were Medically Supervised, using a minimum of five meal replacements per day, and Healthy Solutions, using meal replacements, fruits, and vegetables. Both options included weekly classes, daily records, midweek phone calls, and a minimum physical activity goal of 2,000 kcal/week. The primary outcome was change in body weight with secondary outcomes related to behavioral changes and side effects. Intention-to-treat (ITT) and completer analyses (completed 9 weeks of treatment) were performed. During 13 months, 173 patients met criteria for analysis. They selected either Healthy Solutions: 56 patients (ITT) and 37 completers; or Medically Supervised: 117 patients (ITT) and 93 completers. Mean ([+ or -]standard error) weight losses were: Healthy Solutions: ITT=12.8[+ or -]1.3 kg in 13 weeks and completers=17.0[+ or -]1.4 kg in 18 weeks; Medically Supervised: ITT=16.6[+ or -]1.0 kg in 16 weeks and completers=19.7[+ or -]1.0 kg in 19 weeks. Mean use of meal replacements, fruits, and vegetables exceeded goals. Most side effects were mild and did not affect program continuation. An intensive behavioral weight-loss program using low-energy diets, including five meal replacements daily, is safe and effective. Article History: Accepted 20 February 2009

Life span can be extended in rodents by restricting food availability (caloric restriction [CR]) or by providing food low in methionine (Meth-R). Here, we show that a period of food restriction limited to the first 20 days of life, via a 50% enlargement of litter size, shows extended median and maximal life span relative to mice from normal sized litters and that a Meth-R diet initiated at 12 months of age also significantly increases longevity. Furthermore, mice exposed to a CR diet show changes in liver messenger RNA patterns, in phosphorylation of Erk, Jnk2, and p38 kinases, and in phosphorylation of mammalian target of rapamycin and its substrate 4EBP1, HE-binding protein 1 that are not observed in liver from age- matched Meth-R mice. These results introduce new protocols that can increase maximal life span and suggest that the spectrum of metabolic changes induced by low-calorie and low-methionine diets may differ in instructive ways. Key Words: Methionine--Litter size--Caloric restriction--TOR--ERK.

Calorie restriction (CR) improves health and extends life span in a variety of species. Despite many downstream molecules and physiological systems having been identified as being regulated by CR, the mechanism by which CR extends life span remains unclear. The Drosophila gene Indy (for I'm not dead yet), involved in the transport and storage of Krebs cycle intermediates in tissues important in fly metabolism, was proposed to regulate life span via an effect on metabolism that could overlap with CR. In this study, we report that CR down regulates Indy mRNA expression, and that CR and the level of Indy expression interact to affect longevity. Optimal life span extension is seen when Indy expression is decreased between 25 and 75% of normal. Indy long-lived flies show several phenotypes that are shared by long-lived CR flies, including decreased insulin-like signaling, lipid storage, weight gain, and resistance to starvation as well as an increase in spontaneous physical activity. We conclude that Indy and CR interact to affect longevity and that a decrease in Indy may induce a CR-like status that confers life span extension. Drosophila | insulin | physical activity | triglyceride

Abstract A recently developed oral formulation in the form of coated tablets (Monoselect Camellia®) (MonCam) containing highly bioavailable green tea extract (GreenSelect® Phytosome) was tested in obese subjects (n=100) of [...]

The relationship between thyroid function and leptin has been extensively studied; however, the mechanisms underlying the changes in thyroid hormone economy that occur during caloric deprivation remain elusive. Our goal was to evaluate the thyroid function of rats submitted to 40% food restriction after chronic leptin replacement. Caloric restriction for 25 days led to significantly reduced serum leptin, thyroid-stimulating hormone (TSH), thyroxine ([T.sub.4]), and triiodothyronine ([T.sub.3]) and increased serum corticosterone, while liver, kidney, and thyroid type I deiodinase (D1) and brown adipose tissue (BAT) type II deiodinase (D2) activities were decreased and hypothalamic D2 was significantly increased. Interestingly, thyroid iodide uptake was unchanged by caloric restriction, but thyroperoxidase (TPO) activity was significantly reduced. Leptin replacement for the last 10 days of caloric restriction normalized serum leptin and TSH levels, but serum [T.sub.4] and [T.sub.3] levels and thyroid Dl and TPO activities were not reestablished. Also, a negative effect of leptin administration on [Na.sup.+]-[I.sup.-] symporter function was detected. Liver and kidney D1 and hypothalamic and BAT D2 were normalized by leptin, while pituitary D2 was significantly decreased. In conclusion, a tissue-specific modulation of deiodinases might be implicated in the normalization of thyroid function during leptin replacement in food-restricted rats. Although leptin restores the hypothalamus-pituitary axis during food restriction, it exerts a direct negative effect on the thyroid gland; thus normalization of serum thyroid hormones might depend on changes in deiodinase activities and the long-term thyroid stimulation by TSH to counterbalance the direct negative effects of leptin on the thyroid gland. hypothalamus; pituitary; thyroid; caloric deprivation; thyrotropin

The inbred Lou/C rat, originating from the Wistar strain, has been described as a model of resistance to diet-induced obesity, but little is known about its metabolism. Since this knowledge could provide some clues about the etiology of obesity/insulin resistance, this study aimed at characterizing glucose and lipid metabolism in Lou/C vs. Wistar rats. This was achieved by performing glucose and insulin tolerance tests, euglycemic hyperinsulinemic clamps, and characterization of intracellular insulin signaling in skeletal muscle. Substrate-induced insulin secretion was evaluated using perfused pancreas and isolated islets. Finally, body fat composition and the expression of various factors involved in lipid metabolism were determined. Body weight and caloric intake were lower in Lou/C than in Wistar rats, whereas food efficiency was similar. Improved glucose tolerance of Lou/C rats was not related to increased insulin output but was related to improved insulin sensitivity/responsiveness in the liver and in skeletal muscles. In the latter tissue, this was accompanied by improved insulin signaling, as suggested by higher activation of the insulin receptor and of the Akt/ protein kinase B pathway. Fat deposition was markedly lower in Lou/C than in Wistar rats, especially in visceral adipose tissue. In the inguinal adipose depot, expression of uncoupling protein-1 was detected in Lou/C but not in Wistar rats, in keeping with a higher expression of peroxisome proliferator-activated receptor-[gamma] coactivatot-1 in these animals. The Lou/C rat is a valuable model of spontaneous food restriction with associated improved insulin sensitivity. Independently from its reduced caloric intake, it also exhibits a preferential channeling of nutrients toward utilization rather than storage. metabolism; obesity; animal model

Calorie restriction and reduced somatotropic (growth hormone and insulin-like growth factor-l) signaling have a widespread though not universal ability to extend life. These interventions are considered central tools to understanding the downstream events that lead to the increase in healthy life span. As these approaches have been validated, the animals phenotyped, and the mechanisms proposed, many challenges have emerged. In this article, we give several examples and propose several considerations, opportunities, and approaches that may identify major mechanisms through which these interventions exert their effects, and which may lead to drug therapy to increase 'health span.' Key Words: Healthylife span--Caloric restriction--Growth hormone--Insolin-Like growth fact.

To gain insight into the significance of alterations in the proteasome pathway for sarcopenia and its attenuation by calorie restriction, we examined protein oxidation and components of the proteasome pathway in plantaris muscle in 8-, 30-, and 35-too-old ad libitum-fed (AL) rats; and in 8-, 35-, and 40-mo-old calorie-restricted (CR) rats. We hypothesized that CR rats would exhibit a lesser accumulation of protein carbonyls with aging and that this would be associated with a better maintenance of skeletal muscle proteasome activity and function with aging. Consistent with this view, whereas AL rats had a significant increase in protein carbonylation with aging, there was no such increase in CR rats. Protein levels of the ubiquitin ligases MuRF1 and MAFbx increased similarly with aging in both AL and CR rats. On the other hand, chymotrypsin-like activity of the proteasome increased with aging more gradually in CR rats, and this increase was paralleled by increases in the expression of the C2 subunit in both groups, suggesting that differences in activity were not related to differences in proteasome function with aging. Interestingly, the plot of muscle mass vs. proteasome activity showed that the oldest animals in both diets had a lower muscle mass than would be predicted by their proteasome activity, suggesting that other factors explain the acceleration of sarcopenia at advanced age. Since calorie restriction better protects skeletal muscle function than muscle mass with aging (Hepple RT, Baker DJ, Kaczor JJ, Krause DJ, FASEB J 19: 1320-1322, 2005), and our current results show that this protection of function is associated with a prevention of oxidative protein damage accumulation, we suggest that calorie restriction optimizes the proteasome pathway to preserve skeletal muscle function at the expense of modest muscle atrophy. oxidative stress

Little is known about the effects of weight loss on diastolic function. Furthermore, it is not known whether both caloric restriction (CR)- and exercise (Ex)-induced weight loss have salutary effects on diastolic function. Therefore, we assessed the effects of yearlong CR (n = 12) and Ex (n = 13) interventions, which induced ~12% weight loss, on diastolic function in healthy, nonobese (body mass index = 23.5-29.9 kg/[m.sup.2]) men and women aged 50 to 60 yr. Recordings of Doppler transmittal flow and Doppler tissue imaging were acquired and analyzed by conventional approaches and a validated parameterized diastolic filling (PDF) formalism. Isovolumic relaxation time decreased after weight loss in both groups (P < 0.05). Septal peak early mitral annular velocity (E') increased (P < 0.01) and peak E-wave velocity/E' decreased (P < 0.05) after weight loss in the CR group. Based on the PDF-derived indexes, CR resulted in a decrease in global ventricular stiffness (k) and increases in longitudinal (septal annulus motion) stored elastic strain ([x'.sub.o]), peak force (k'[x.sub.o]), and peak stored strain energy (1/2k' [x'.sub.o.sup.2]). In the Ex group, k was unchanged, although septal [x'.sub.o] and 1/2k' [x'.sub.o.sup.2] increased significantly and k'[x'.sub.o] (P = 0.13) tended to increase. We conclude that weight loss, whether induced by CR or Ex, has salutary effects on diastolic function. diet; echocardiography; tissue Doppler imaging: diastole

The mortality of a population reflects the combined effects of natural aging with environmental insults (e.g. toxicant exposure, caloric restriction, over feeding, infections, etc.). No single endpoint, such as carcinogenesis, completely describes toxicant-induced effects in laboratory animals. Mathematical models of mortality and time-dependent exposure to toxicants can yield indices of net injury from all causes. With careful manipulation of diet in control groups, the separate and combined effects of hormesis, caloric restriction and toxicity on mortality can be delineated. In particular, age-specific mortality rate analyses can characterize a) the temporal pattern of net injury from acute, short term and chronic environmental exposure, b) late-life effects, c) effects of fractional exposures and d) relative biological effectiveness. Changes in the design of toxicity studies and analyses of mortality data are suggested. Key words: Hormesis, caloric restriction, mortality, chronic toxicity, INTRODUCTION Hormesis and caloric restriction have been considered as related phenomena in laboratory rodents (see Human and Experimental Toxicology vol. 19 no 6, 2000). [1] Laboratory rodents are typically inbred [...]

Caloric restriction has wide-ranging health benefits and may offer protection against age-related neuronal loss and neurodegenerative disorders such as Alzheimer's disease, possibly via enhanced adult neurogenesis. While a variety of interventions such as exercise increase neurogenesis, recent work suggests that exercise and caloric restriction may work to enhance neurogenesis by different neurobiological mechanisms, suggesting a role for both diet and exercise in disease prevention. Key words: brain-derived neurotrophic factor, dietary restriction, neurogenesis, neurotrophins, neurological diseases, N-methyl-D-aspartate, stem cells

ABSTRACT Background Caloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria. However, the mechanism responsible [...]

The effects of 6 months of calorie restriction, with or without exercise, in overweight, nonobese men and women are examined. Results reveal that 2 biomarkers of longevity (fasting insulin level and body temperature) are decreased by prolonged calorie restriction in humans and support the theory that metabolic rate is reduced beyond the level expected from reduced metabolic mass.

Women with high dietary restraint typically report restricting energy intake and using reduced-kilocalorie foods in an effort to achieve or maintain a certain body weight. However, previous studies of food choices associated with dietary restraint have been limited by the self-report of participants' food selections. We provided all foods consumed during a free-living 24-hour period to 62 normal-weight women with high (n=33) or low (n=29) dietary restraint, and observed choices from among similar foods varying in fat, fiber, and energy content. Women with high dietary restraint consumed less energy and chose reduced-kilocalorie and reduced-fat foods more frequently than unrestrained eaters. Group differences in choices of milk, cream cheese, mayonnaise, salad dressing, and soda were noted. Dietitians may consider frequent use of reduced-kilocalorie and reduced-fat foods a potential indicator of high dietary restraint, which may have health consequences. Accordingly, further exploration of clients' tendency to restrict dietary intake may be warranted. J Am Diet Assoc. 2004;104:1154-1157.

Objective: To address the clinical implications of leptin and to re-examine the relationship between leptin and its potential humoral regulators such as insulin, nonesterified fatty acids (NEFA) and triiodothyronine (T3) in low-calorie diet (LCD) for obese humans. Design: Longitudinal study. Setting: University and foundation hospitals. Subjects: Ten obese men and 10 premenopausal obese women. Interventions: Five men and five women took 800 kcal/day LCD and another five men and five women took 1400 kcal/day balanced deficit diet (BDD) during 4 weeks. Results: Plasma leptin levels in the LCD group decreased more markedly (46.2 [+ or -] 14.6 to 13.2 [+ or -] 3.6 ng/ml) than that expected for the decrement in percentage fat (39.0 [+ or -] 1.7 to 35.9 [+ or -] 1.7%) and body mass index (BMI; 35.4 [+ or -] 2.4 to 33.1 [+ or -] 2.2 kg/[m.sup.2]), while that in the BDD group did not decrease significantly (14.9 [+ or -] 3.5 to 13.4 [+ or -] 2.8 ng/ml). The ratio of the decrease in leptin levels to that of BMI during the first week was significantly greater than that during the following 3 weeks (39.5 [+ or -] 2.7 vs 29.3 [+ or -] 2.1%, P=0.017). The plasma insulin and T3 levels also fell substantially in the first week and continued to decrease during the entire course. Plasma leptin levels measured weekly in each subject were correlated well with insulin (r=0.586, P=0.0003) and T3 (r=0.785, P=0.0004). Multiple regression analyses after adjustment for the time course and BMI revealed that serum levels of T3 were independently correlated with plasma leptin levels (r=0.928, P Conclusions: A rapid fall in leptin during the first week of LCD, coordinated by insulin, T3 and NEFA, should be beneficial for responding to decreased energy intake. Inversely, in view of the powerful effect of leptin on energy dissipation, the present findings suggest the potential usefulness of leptin in combination with caloric restriction for the treatment of obesity. Sponsorship: The Ministry of Education, Culture, Sports, Science and Technology of Japan and the Ministry of Health, Labour and Welfare of Japan. doi:10.1038/sj.ejcn.1601363 Keywords: leptin; insulin; triiodothyronine (T3); nonesterified fatty acids (NEFA); diet therapy, Introduction Obesity is an increasingly prevalent, costly and important health problem throughout the world (Anderson & Kannel, 1992). Although novel therapeutic modalities against obesity have been expected, the low calorie [...]

Most comprehensive study yet demonstrates that cutting people's energy intake dials down their metabolism. Most comprehensive study yet demonstrates that cutting people's energy intake turns down their metabolism., Author(s): Alison Abbott Author Affiliations: Reduced-calorie diet shows signs of slowing ageing in people Several studies are examining the effects of reducing calorie consumption on people's metabolism. Credit: Carlos Sanchez [...]