Caloric restriction-mimetics for the reduction of heart failure risk in aging heart: with consideration of gender-related differences

The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease(CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction(CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas:(1) mechanisms underlying age-related cardiac remodeling;(2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women;(3) we select a few polyphenol or polyamine rich compounds as the CRmimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.

The effect of caloric restriction on genetical pathways

Energy restriction is defined as reducing nutrient intake without dragging the organism into malnutrition. Energy restriction is preferred because it is a non-genetic intervention that increases life expectancy. Nicotinamide adenine dinucleotide(NAD~+)and adenosine monophosphate(AMP)levels, which are the indicators of intracellular energy deficiency, increase with energy restriction. The increase in NAD~+ level stimulates sirtuin(SIRT)enzymes, and the increase in AMP level stimulates AMP-activated protein kinase(AMPK). Various mechanisms are regulated by stimulating these enzymes. By Forkhead box O(FoxO)transcription factors, the ability of resistance to oxidative stress increases, and antioxidant genes, DNA repair, and autophagy genes are stimulated. Apoptosis is induced by stimulation of the p53 protein, and tumor growth is suppressed by the disruption of aging cells. The suppression of phosphoinositide 3-kinase(PI3K)-/-Akt, and therefore mTOR signal stimulates autophagy and mitophagia, and cleanses damaged cells and organelles. Mitochondrial biogenesis is stimulated, antioxidant capacity increases, and inflammatory response decreases. Adipose tissue and lipid metabolism are regulated by the regulation of fatty acid synthesis and oxidation. As a consequence, the effects of caloric restriction on cellular metabolism are regulated through the genetic pathways.

Weight Loss and Improved Metabolic Health Measures Using a One-Week Active Nutrition Jumpstart Program in Overweight and Obese Men and Women

Background: The prevalence of individuals who are obese or overweight is an increasing global epidemic that is associated with a multitude of adverse health conditions. Multiple strategies are available to promote weight loss in these populations, including the use of caloric restriction and/or liquid diets. We determined the impact of a low-calorie, nutrient-dense, primarily liquid diet on body weight and associated measures of metabolic health in overweight and obese men and women. Methods: Twenty-six men and women (age: 42.6 ± 10.8) completed a seven-day intervention using the USANA Active Nutrition Jumpstart program, which consisted of consuming three meal replacement shakes and three to four servings of fruits and vegetables, along with a probiotic, three metabolism supplements, and two vitamin packs each day. Pre-post measurements included body composition—determined (via DXA), fasting levels of lipids and glucose in heparinized whole blood, weight, waist circumference, hip circumference, heart rate, and blood pressure. Subjective mood and hunger were also assessed. Results: The dietary program was well-tolerated, and the intervention resulted in a mean weight loss of approximately 4.5 pounds. Clinically relevant reductions were noted in systolic and diastolic blood pressure, cholesterol (total and LDL), and glucose. In addition, there were favorable changes in self-esteem, energy, motivation, and physical appearance. Conclusion: A one-week period of adherence to the Active Nutrition Jumpstart program positively impacted subjective feelings, while resulting in significant weight loss and other health benefits that may have clinical relevance. Longer-term interventions are needed to sustain these initial results.

Effects of ultrasound monitoring of gastric residual volume on feeding complications,caloric intake and prognosis of patients with severe mechanical ventilation

BACKGROUND Monitoring of gastric residual is an important approach for assessing gastric emptying in patients with mechanical ventilation.By monitoring gastric contents,the enteral nutrition scheme can be adjusted in time to ensure feeding safety.AIM To investigate the effects of ultrasound monitoring on the incidence of feeding complications,daily caloric intake and prognosis of patients with severe mechanical ventilation.To analyze the clinical significance of ultrasound monitoring of gastric residual volume(GRV)up to 250 mL to provide a theoretical basis for clinical practice.METHODS Patients admitted to the department of emergency medicine of the Affiliated Hospital of Nantong University from January 2018 to June 2022 who received invasive mechanical ventilation and continuous enteral nutrition support within 24-48 h after admission were enrolled in this study.Medical records for patients within 7 d of hospitalization were retrospectively analyzed to compare the incidence of feeding complications,daily caloric intake and clinical prognosis between patients with gastric residual≥250 mL and<250 mL,as monitored by ultrasound on the third day.RESULTS A total of 513 patients were enrolled in this study.Incidences of abdominal distension,diarrhea,and vomiting in the<250 mL and≥250 mL groups were:18.4%vs 21.0%,23.9%vs 32.3%and 4.0%vs 6.5%,respectively;mortality rates were 20.8%vs 22.65%;mechanical ventilation durations were 18.30 d vs 17.56 d while lengths of stay in the intensive care units(ICU)were 19.87 d vs 19.19±5.19 d.Differences in the above factors between groups were not significant.Gastric residual≥250 mL was not an independent risk factor for death and prolonged ICU stay.However,target feeding time of patients in the≥250 mL group was longer than that of patients in the≥250 mL group,and caloric intake(22.0,23.6,24.8,25.3 kcal/kg/d)for patients in the≥250 mL group from the 4^(th) day to the 7^(th) day of hospitalization was lower than that of patients in the≥250 mL group(23.2,24.8,25.7,25.8 kcal/kg/d).On the 4^(th) day(Z=4.324,P=0.013),on the 5^(th) day(Z=3.376,P=0.033),while on the 6^(th) day(Z=3.098,P=0.04),the differences were statistically significant.CONCLUSION The use of ultrasound to monitor GRV and undertaking clinical interventions when the monitoring value is≥250 mL has no significant effects on incidences of feeding complications and clinical prognostic outcomes,however,it significantly prolongs the time to reach target feeding,reduces the daily intake of calories during ICU hospitalization,and increases the risk of insufficient nutrition of patients.The accuracy and necessity of monitoring gastric remnants and monitoring frequencies should be investigated further.

Supersonic Two-Dimensional Minimum Length Nozzle Design at High Temperature. Application for Air

When the stagnation temperature of a perfect gas increases, the specific heat ratio does not remain constant any more, and start to vary with this temperature. The gas remains perfect, its state equation remains always valid, except it will name in more calorically imperfect gas or gas at High Temperature. The goal of this work is to trace the profiles of the supersonic Minimum Length Nozzle with centered expansion when the stagnation temperature is taken into account, lower than the threshold of dissociation of the molecules and to have for each exit Mach number several nozzles shapes by changing the value of the temperature. The method of characteristics is used with a new form of the Prandtl Meyer function at high temperature. The resolution of the obtained equations is done by the second order of fmite differences method by using the predictor corrector algorithm. A study on the error given by the perfect gas model compared to our model is presented. The comparison is made with a calorically perfect gas for goal to give a limit of application of this model. The application is for the air.

Effect of Stagnation Temperature on the Supersonic Two-Dimensional Plug Nozzle Conception. Application for Air

When the stagnation temperature of a perfect gas increases, the specific heats and their ratio do not remain constant any more and start to vary with this temperature. The gas remains perfect, its state equation remains always valid, except it will name in more calorically imperfect gas or gas at High Temperature. The goal of this research is to trace the profiles of the supersonic plug nozzle when this stagnation temperature is taken into account, lower than the threshold of dissociation of the molecules, by using the new formula of the Prandtl Meyer function, and to have for each exit Mach number, several nozzles shapes by changing the value of this temperature. A study on the error given by the PG （perfect gas） model compared to our model at high temperature is presented. The comparison is made with the case of a calorically perfect gas aiming to give a limit of application of this model. The application is for the air.

Net energy of corn,soybean meal and rapeseed meal in growing pigs

Background: Two experiments were conducted to estimate the net energy(NE) of corn, soybean meal, expel er-pressed rapeseed meal(EP-RSM) and solvent-extracted rapeseed meal(SE-RSM) using indirect calorimetry and to validate the NE of these four ingredients using pig growth performance.Methods: In Exp.1, 24 barrows(initial BW = 36.4 ± 1.6 kg) were allotted to 1 of 4 diets which included a corn basal diet,a corn-soybean meal basal diet and two rapeseed meal diets containing 20% EP-RSM(9.5% ether extract) or SE-RSM(1.1% ether extract) substituted for corn and soybean meal. The design allowed the calculation of NE values of corn,soybean meal and rapeseed meals according to the difference method. In Exp.2, 175 growing pigs(initial BW = 36.0± 5.2 kg) were fed 1 of 5 diets for 28 d, with five pigs per pen and seven replications(pens) per treatment in order to validate the measured energy values. Diets were a corn-soybean meal diet and four diets including 10% or 20% EP-RSM and 10% or 20% SE-RSM.Results: The NE of corn, soybean meal, EP-RSM and SE-RSM were 12.46, 11.34, 11.71 and 8.83 MJ/kg DM, respectively. The NE to ME ratio of corn(78%) was similar to tabular values, however, the NE to ME ratios of soybean meal(70%) and rapeseed meal(76%) were greater than tabular values. The greater NE value in EP-RSM than in SE-RSM is consistent with its higher EE content. Increasing EP-RSM or SE-RSM did not affect the growth performance of pigs and the caloric efficiency of NE was comparable for al diets.Conclusions: The NE of EP-RSM was similar to soybean meal, and both were greater than SE-RSM. The DE, ME and NE values measured in Exp.1 are confirmed by results of Exp. 2 with comparable caloric efficiencies of DE, ME or NE for all diets.

Role of diet and lifestyle changes in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD)has becomeone of the most common causes of liver disease worldwide and has been recognized as a major health burden.The prevalence of NAFLD has grown proportionallywith the rise in obesity,sedentary lifestyle,unhealthydietary pattern,and metabolic syndrome.Currently,there is no drug therapy that can be formulated fortreating NAFLD.A combination of dietary modificationsand increased physical activity remains the mainstayof NAFLD management.It is hard to maintain thismode of management;however,it seems to havesignificant long-term benefits.Furthermore,NAFLDpatients,whether obese or not,should be educatedthat a healthy diet and physical activity have benefitsbeyond weight reduction.Further large controlled randomized trials are needed in order to identify the bestdietary regimen and physical activity in the management of NAFLD patients.This review highlights the roleof diet and lifestyle modifications in the managementof NAFLD,and focuses on human studies regarding dietary modifications and physical activity.

Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer＇s disease

Alzheimer’s disease （AD） is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons. The pathophysiology of AD is complex; mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress are antecedent and potentially play a causal role in the disease pathogenesis. Dysfunctional mitochondria accumulate from the combination of impaired mitophagy, which can also induce injurious inflammatory responses, and inadequate neuronal mitochondrial biogenesis. Altering the metabolic capacity of the brain by modulating/potentiating its mitochondrial bioenergetics may be a strategy for disease prevention and treatment. We present insights into the mechanisms of mitochondrial dysfunction in AD brain as well as an overview of emerging treatments with the potential to prevent, delay or reverse the neurodegenerative process by targeting mitochondria.

A review of feed efficiency in swine:biology and application

Feed efficiency represents the cumulative efficiency with which the pig utilizes dietary nutrients for maintenance, lean gain and lipid accretion. It is closely linked with energy metabolism, as the oxidation of carbon-containing components in the feed drive all metabolic processes. While much is known about nutrient utilization and tissue metabolism, blending these subjects into a discussion on feed efficiency has proven to be difficult. For example, while increasing dietary energy concentration will almost certainly increase feed efficiency, the correlation between dietary energy concentration and feed efficiency is surprisingly low. This is likely due to the plethora of non-dietary factors that impact feed efficiency, such as the environment and health as well as individual variation in maintenance requirements, body composition and body weight. Nonetheless, a deeper understanding of feed efficiency is critical at many levels. To individual farms, it impacts profitability. To the pork industry, it represents its competitive position against other protein sources. To food economists, it means less demand on global feed resources. There are environmental and other societal implications as well. Interestingly, feed efficiency is not always reported simply as a ratio of body weight gain to feed consumed. This review will explain why this arithmetic calculation, as simple as it initially seems, and as universally applied as it is in science and commerce, can often be misleading due to errors inherent in recording of both weight gain and feed intake. This review discusses the importance of feed efficiency, the manner in which it can be measured and reported, its basis in biology and approaches to its improvement. It concludes with a summary of findings and recommendations for future efforts.

Protective effects of estrogens and caloric restriction during aging on various rat testis parameters

Aim： To investigate the effects of 17β-estradiol （E2）, Peganum harmala extract （PHE） and caloric restriction （CR） on various testis parameters during aging. Methods： Twelve-month-old male rats were treated for 6 months with either E2 or PHE, or submitted to CR （40%）. Results： Our results show that estrogens and CR are able to protect the male gonad by preventing the decrease of testosterone and E2 levels as well as the decrease of aromatase and estrogen receptor gene expressions. Indeed, E2, PHE and CR treatments induced an increase in the superoxide dismutase activities and decreased the activity of testicular enzymes： gamma-glutamyl transferase, alkaline phosphatase, lactate deshydrogenase as well as the aspartate and lactate transaminases in aged animals. In addition, the testicular catalase and gluthatione peroxidase activities were enhanced in E2, PHE and CR-treated rats compared to untreated animals at 18 months of age. Moreover, the positive effects of estradiol, PHE and CR were further supported by a lower level of lipid peroxidation. Recovery of spermatogenesis was recorded in treated rats. Conclusion： Besides a low caloric diet which is beneficial for spermatogenesis, a protective antioxydant role of estrogens is suggested. Estrogens delay testicular cell damage, which leads to functional senescence and, therefore, estrogens are helpful in protecting the reproductive functions from the adverse effects exerted by reactive oxygen species （ROS） produced in large quanti- ties in the aged testis.

Intermittent energy restriction in type 2 diabetes: A short discussion of medication management

AIM To discuss type 2 diabetes mellitus(T2DM) medication changes required during the popular 5:2 intermittent energy restriction(IER) diet. METHODS A search was conducted in MEDLINE, EMBASE, AMED, CINAHL and Cochrane library for original research articles investigating the use of very low calorie diets(VLCD) in people with T2 DM. The search terms used included "VLCD" or "very low energy diet" or "very low energy restriction" or "IER" or "intermittent fasting" or "calorie restriction" or "diabetes mellitus type 2" and "type 2 diabetes". Reference lists of selected articles were also screened for relevant publications. Only research articles written in English, which also included an explanation of medication changes were included. A recent pilot trial using the 5:2 IER method, conducted by our research group, will also be summarized.RESULTS A total of 8 studies were found that investigated the use of VLCD in T2 DM and discussed medication management. Overall these studies indicate that the use of a VLCD for people with T2 DM usually require the cessation of medication to prevent hypoglycemia. Therefore, the 5:2 IER method will also require medication changes, but as seen in our pilot trial, may not require total cessation of medication, rather a cessation on the 2 IER days only. CONCLUSION Guidelines outlined here can be used in the initial stages of a 2-d IER diet, but extensive blood glucose monitoring is still required to make the necessary individual reductions to medications in response to weight loss.

Strategies to improve regenerative potential of mesenchymal stem cells

In the last few decades,stem cell-based therapies have gained attention worldwide for various diseases and disorders.Adult stem cells,particularly mesenchymal stem cells(MSCs),are preferred due to their significant regenerative potential in cellular therapies and are currently involved in hundreds of clinical trials.Although MSCs have high self-renewal as well as differentiation potential,such abilities are compromised with“advanced age”and“disease status”of the donor.Similarly,cell-based therapies require high cell number for clinical applications that often require in vitro expansion of cells.It is pertinent to note that aged individuals are the main segment of population for stem cell-based therapies,however;autologous use of stem cells for such patients(aged and diseased)does not seem to give optimal results due to their compromised potential.In vitro expansion to obtain large numbers of cells also negatively affects the regenerative potential of MSCs.It is therefore essential to improve the regenerative potential of stem cells compromised due to“in vitro expansion”,“donor age”and“donor disease status”for their successful autologous use.The current review has been organized to address the age and disease depleted function of resident adult stem cells,and the strategies to improve their potential.To combat the problem of decline in the regenerative potential of cells,this review focuses on the strategies that manipulate the cell environment such as hypoxia,heat shock,caloric restriction and preconditioning with different factors.

Age-related decrease in aromatase and estrogen receptor （ERα and ERβ） expression in rat testes： protective effect of low caloric diets

Aim： To examine the effects on rat aging of caloric restriction （CR1） and undernutrition （CR2） on the body and on testicular weights, on two enzymatic antioxidants （superoxide dismutase and catalase）, on lipid peroxidation and on the expression of testicular aromatase and estrogen receptors （ER）. Methods： CR was initiated in 1-month-old rats and carried on until the age of 18 months. Results： In control and CR2 rats an age-related decrease of the aromatase and of ER （α and β） gene expression was observed; in parallel a diminution of testicular weights, and of the total number and motility of epididymal spermatozo was recorded. In addition, aging in control and CR2 rats was accompartied by a significant decrease in testicular superoxide dismutase, catalase activities, and an increase in lipid peroxidation level （thiobarbituric acid reactive substance）, associated with alterations of spermatogenesis. Conversely, caloric restriction-treatment exerted a protective effect and all the parameters were less affected by aging. Conclusion： These results indicate that during aging, a low caloric diet （not undernutrition） is beneficial for spermatogenesis and likely improves the protection of the cells via an increase of the cellular antioxidant defense system in which aromatase/ ER could play a role. （Asian J Andro12008 Mar; 10： 177-187）

Autonomic laterality in caloric vestibular stimulation

BACKGROUND Caloric stimulation of the vestibular system is associated with autonomic response.The lateralization in the nervous system activities also involves the autonomic nervous system.AIM To compare the effect of the right and left ear caloric test on the cardiac sympathovagal tone in healthy persons.METHODS This self-control study was conducted on 12 healthy male volunteers.The minimal ice water caloric test was applied for vestibular stimulation.This was done by irrigating 1 milliliter of 4±2°C ice water into the external ear canal in 1 s.In each experiment,only one ear was stimulated.For each ear,the pessimum position was considered as sham control and the optimum position was set as caloric vestibular stimulation of horizontal semicircular channel.The order of right or left caloric vestibular stimulation and the sequence of optimum or pessimum head position in each set were random.The recovery time between each calorie test was 5 min.The short-term heart rate variability(HRV)was used for cardiac sympathovagal tone metrics.All variables were compared using the analysis of variance.RESULTS After caloric vestibular stimulation,the short-term time-domain and frequencydomain HRV indices as well as,the systolic and the diastolic arterial blood pressure,the respiratory rate and the respiratory amplitude,had no significant changes.These negative results were similar in the right and the left sides.Nystagmus duration of left caloric vestibular stimulations in the optimum and the pessimum positions had significant differences(e.g.,72.14±39.06 vs 45.35±35.65,P<0.01).Nystagmus duration of right caloric vestibular stimulations in the optimum and the pessimum positions had also significant differences(e.g.,86.42±67.20 vs 50.71±29.73,P<0.01).The time of the start of the nystagmus following caloric vestibular stimulation had no differences in both sides and both positions.CONCLUSION Minimal ice water caloric stimulation of the right and left vestibular system did not affect the cardiac sympathovagal balance according to HRV indices.

Assessment of Gross Chemical Composition, Mineral Composition, Vitamin Composition and Amino Acids Composition of Wheat Biscuits and Wheat Germ Fortified Biscuits

Wheat germ is reckoned valuable healthful functional food. The present investigation was performed to assess nutritional status of wheat biscuits and wheat germ fortified biscuits. Study included determination of gross chemical composition, caloric value, minerals (Mn, Ca, Fe, Cu, P, Na and K), vitamins (C, Folic acid, A, and E), and amino acid composition of wheat biscuits and 15%, 20% wheat germ fortified biscuits. Likewise physical and sensory characteristics of studied biscuits were assessed. The data revealed that 20% wheat germ fortified biscuits proved to be nutritious functional healthful food. It improved both physical, sensory characteristics and recorded the highest crude protein (12.20%), crude fiber (2%), and the least fat (9.63%), moisture (3.01%), and caloric value (436.31 Kcal/100g). While it recorded the highest Mn and Cu contents as well as increased vitamins C, Folic acid, A, and E. Besides, 20% wheat germ fortified biscuits increased all the eight essential amino acids contents resulting in an improvement of the nutritive value of wheat biscuits. Therefore it could be recommended for caloric reduced diets for obese and overweight persons. Likewise, it should be increasing interest as an ingredient in the industry as functional and healthy foods formulations as biscuits, bread and cakes.

The promise of neuroprotection by dietary restriction in glaucoma

Glaucoma,a progressive age-related optic neuropathy characterized by the death of retinal ganglion cells,is the most common neurodegenerative cause of irreversible blindness worldwide.The therapeutic management of glaucoma,which is limited to lowering intraocular pressure,is still a challenge since visual loss progresses in a significant percentage of treated patients.Restricted dietary regimens have received considerable attention as adjuvant strategy for attenuating or delaying the progression of neurodegenerative diseases.Here we discuss the literature exploring the effects of modified eating patterns on retinal aging and resistance to stressor stimuli.

体育教学中影响学生热量消耗的因素(英文)

Background:Increasing caloric expenditure in physical education is considered an effective school-based approach to addressing the child obesity epidemic.This study was designed to determine synergistic influences of student characteristics and lesson factors on caloric expenditure in elementary and middle school physical education. Methods:The study used a multi-level design.Level-1 factors included personal characteristics:age,gender,and body mass index.Level-2 factors included lesson length,content,and school level.Based on the Center for Disease Control and Prevention age—gender adjusted growth chart,students in 87 classes from 14 elementary and 15 middle schools were pre-screened into "Overweight","Healthy weight",or "Thin" groups.One boy and one girl were randomly selected from each group in each class as data providers(264 elementary and 294 middle school students).Caloric expenditure was measured in 243 physical education lessons using accelerometers. Results:Analysis of variance revealed and hierarchical linear modeling confirmed separate age by body mass index,age by gender,and content by lesson—length interaction effects,suggesting that the personal and lesson factors influenced caloric expenditure independently.Older male and heavier students burned more calories in all lessons.Students burned more calories in 45—60 min sport skill or fitness lessons than in shorter (30 min) or longer(75—90 min) game or multi-activity lessons. Conclusions:The hypothesized cross-level interaction was not observed in the data.Caloric expenditure can be optimized in 45—60 min sport skill or fitness development lessons.It can be recommended that schools adopt 45—60 min lesson length and provide skill and fitness development tasks in physical education to maximize caloric expenditure.

Concerns about the misleading conclusions regarding estimation of the net energy value of soybean meal relative to corn using the caloric efficiency approach in pigs

Apart from energy balance trials such as calorimetry,growth trials could also be used to estimate the energy values of feed ingredients with caloric efficiency as an indicator.Recent work used such methods reported greater net energy(NE)value of soybean meal(SBM)relative to corn in nursery pigs.We theoretically compared the NE values of SBM and corn according to the definition of NE and properties of the major chemical compositions in each ingredient.Meanwhile,we thoroughly examined the diet formulations and related analysis used in this work and compared this study with some peer works.We found that this study may suffer from problems with experimental design,reference citation,and data interpretation.In summary,the conclusion from the recent work that the SBM NE value may be greater than the corn NE value is likely to be erroneous.

Gestational 营养和肥胖的发展在成人生活期间

Recent epidemiological studies indicate a strong linkbetween intrauterine under-nutrition and propensityof such off spring for developing obesity and meta-bolic syndrome in later life. Garg et al investigated the mechanistic basis of this phenomenon and its potential reversibility in rats. The authors found that rats experiencing gestational under-nutrition but fed normally after birth (IUGR) gained body mass with excessive subcutaneous and visceral fat. The IUGR rats were alsome tabolically inflexible since they showed similar rates of energy expenditure and O2consumption in the fedand fasted states. However, if such pups were food-restricted during lactation (PNGR), their metabolic profiles resembled those of control and IPGR (subject tofood restriction during pre- and postnatal periods) rats.Thus, postnatal caloric restriction superimposed on intrauterine under nutrition significantly improved insulinsensitivity and adiposity of rats that would otherwise develop metabolic inflexibility and visceral obesity. The observations of Garg et al , have serious implications interm of the design of the future experimental studiesas well as their clinical translation in humans.