Short-term Food Restriction Research Articles

Short-term control of diet affects cisplatin-induced acute kidney injury through modulation of mitochondrial dynamics and mitochondrial GSH.

Obesity affects acute kidney injury (AKI) induced by various clinical settings, including transplantation and cisplatin‐cancer therapy. However, the effect of short‐term food intake change remains to be defined. Here, we investigated the effects of short‐term high‐fat diet intake and food restriction on cisplatin‐induced AKI. Mice were fed either a high‐fat diet (HFD) or a low‐fat diet (LFD) for 11 days or were not fed for 40 hh (fasting), before cisplatin administration. Cisplatin‐induced functional and structural damages to kidneys in both HFD‐ and LFD‐fed mice, with greater damages in HFD‐fed mice than LFD‐fed mice. HFD decreased mitochondrial total glutathione (tGSH) level, along with increases in the plasma and kidney cholesterol levels. Cisplatin caused the increase of kidney cholesterol levels and oxidative stress, along with the decrease of mitochondrial tGSH levels. In addition, cisplatin‐induced mitochondrial damage and apoptosis of tubular cells in both HFD‐ and LFD‐fed mice. An increase of Fis1 (mitochondria fission 1 protein), whereas a decrease of Opa1 (mitochondria fusion 1 protein) occurred by cisplatin. These cisplatin effects were greater in HFD‐fed mice than in LFD‐fed mice. Administration of mitochondria‐specific antioxidant treatment during HFD feeding inhibited these cisplatin‐induced changes. Fasting for 40 h also significantly reduced the cisplatin‐induced changes mentioned above. These data demonstrate that short‐term HFD intake worsens cisplatin‐induced oxidative stress by the reduction of mitochondrial tGSH, resulting in increased cisplatin‐induced nephrotoxicity. These data newly indicate that the control of calorie intake, even for a short period, affects kidney susceptibility to injury. Although most studies described the effects of a long‐term high‐fat diet on the kidneys, in this study, we found that even if a high‐fat diet was consumed for a short‐term, physiological changes and mitochondria tGSH decrease in the kidneys, and consequently increased cisplatin‐nephrotoxic susceptibility. These data suggest the association of calorie intake with kidney susceptibility to cisplatin.

Effects of cyclical short-term fasting and refeeding on juvenile Lophiosilurus alexandri, a carnivorous Neotropical catfish

The effects of different feeding strategies on the growth rate and hematology of Lophiosilurus alexandri were investigated. An experiment was carried out at the Laboratório de Aquacultura, Universidade Federal Minas Gerais, with nine hundred juvenile L. alexandri (length 4.3 ± 0.3, weight cm 0.9 ± 0.2 g) fed exclusively extruded dry diet and kept in fifteen 30-L cultivation tanks in a recirculating aquaculture system. The design was completely randomized with five replicates of each of three feeding treatments: every day of the week (control), six days of the week (F6:1) and five days of the week (F5:2). The following were calculated at the end of the experiment: survival, daily weight gain (DWG), total length (TL), daily feed intake (DFI), feed conversion rate (FCR), specific growth rate (SGR), final body weight (FBW), condition factor (K), protein efficiency ratio (PER), nitrogen retention (NR) and the hepatosomatic index (HSI). Blood samples were taken after 42 days (prior to feed restriction) and at 45 days (after feed restriction of one or two days), and levels of hematocrit, total plasma, hemoglobin, erythrocytes, leukocytes glucose, cholesterol and triglycerides determined. Data were submitted to ANOVA and means compared by the Tukey test (5%). No significant differences were found for survival, FCR, DWG, TL, FBW, K, and SGR. The highest DFI and HSI values were recorded in the control treatment, while PER and NR were highest in the F5.2 treatment. The highest hematocrit values were observed for the control and F6:1 treatments. In all treatments, the values for hematocrit, total protein, leukocytes and glucose were lower after fasting. The highest values for leukocytes were for the control and F6.1 treatments prior to fasting, while after fasting the control treatment was highest. For the F5:2 treatment, the highest value for erythrocytes was after fasting. The highest values for cholesterol were after fasting for all treatments. In conclusion, L. alexandri exhibits compensatory growth in relation to the two short-term food restriction treatments tested. The species adapted to dietary strategies and maintained hematological and biochemical parameters close to those of the control groups when returned to feeding.

Metabolic profile and spontaneous physical activity modulation under short-term food restriction in young rats.

Abstract AIMS The aim of this study was to investigate the effects of short-term food restriction (6-weeks) on metabolic profile and spontaneous physical activity (SPA) of young male Wistar rats. METHODS Thirty rats had their baseline SPA measured at 21 days-old and were separated into two groups at 28 days-old: Control (CG) and 50% of food restriction (FR). The food restriction protocol lasted six weeks, being the SPA measured weekly by a gravimetric apparatus. At the end of the experiment, biochemical analyses were performed in serum and tissue samples with statistical significance set at 5%. RESULTS FR showed less SPA than CG, as occurred for body mass, water intake, adipose tissue and liver, heart and soleus glycogen, serum glucose, total protein, triglycerides and total cholesterol (P<0.05). CONCLUSION Data set demonstrates that low substrate stores signaled to decrease spontaneous physical activity to save energy.

The effect of short-term food restriction on the metabolic cost of the acute phase response in the fish-eating Myotis (Myotis vivesi)

Food restriction affects the activation of the immune system although the metabolic cost associated with mounting such a response has rarely been examined except in model animals. Wild animals are constantly exposed to variations in the availability of food resources and they need to balance their energy budget to fight against pathogens. We examined the effect of food restriction in the fish eating Myotis (Myotis vivesi), a species of bat that experiences periods in which foraging is limited due to ambient conditions. We tested the hypothesis that acute food restriction (∼65% restriction for 1 night) would reduce the caloric response to lipopolysaccharidae (LPS) injection compared to bats fed ad libitum. We also measured a proxy for body temperature (Tskin) and expected reduced fever development when food intake was limited. Bats on the restricted diet had similar resting metabolic rate, total caloric cost and Tskin after the LPS challenge than when fed ad libitum. However, there was a delay in the metabolic and pyrogenic responses when bats were on the restricted diet. The effect of acute food restriction in delaying the hyperthermia development in fish eating Myotis might be of importance for its capacity to fight pathogens. Similar to other bats, the fish eating Myotis can fast for several consecutive days by entering torpor and future work is warranted to understand the effect of long periods of food restriction on bat immune response.

State-dependent behavior and alternative behavioral strategies in brown trout (Salmo trutta L.) fry.

Animals generally adjust their behavior in response to bodily state (e.g., size and energy reserves) to optimize energy intake in relation to mortality risk, weighing predation probability against the risk of starvation. Here, we investigated whether brown trout Salmo trutta adjust their behavior in relation to energetic status and body size during a major early-life selection bottleneck, when fast growth is important. Over two consecutive time periods (P1 and P2; 12 and 23 days, respectively), food availability was manipulated, using four different combinations of high (H) and low (L) rations (i.e., HH, HL, LH, and LL; first and second letter denoting ration during P1 and P2, respectively). Social effects were excluded through individual isolation. Following the treatment periods, fish in the HL treatment were on average 15–21 % more active than the other groups in a forced open-field test, but large within-treatment variation provided only weak statistical support for this effect. Furthermore, fish on L-ration during P2 tended to be more actively aggressive towards their mirror image than fish on H-ration. Body size was related to behavioral expression, with larger fish being more active and aggressive. Swimming activity and active aggression were positively correlated, forming a behavioral syndrome in the studied population. Based on these behavioral traits, we could also distinguish two behavioral clusters: one consisting of more active and aggressive individuals and the other consisting of less active and aggressive individuals. This indicates that brown trout fry adopt distinct behavioral strategies early in life.Significance statementThis paper provides information on the state-dependence of behavior in animals, in particular young brown trout. On the one hand, our data suggest a weak energetic state feedback where activity and aggression is increased as a response to short term food restriction. This suggests a limited scope for behavioral alterations in the face of starvation. On the other hand, body size is linked to higher activity and aggression, likely as a positive feedback between size and dominance.The experiment was carried out during the main population survival bottleneck, and the results indicate that growth is important during this stage, as 1) behavioral compensation to increase growth is limited, and 2) growth likely increases the competitive ability. However, our data also suggests that the population separates into two clusters, based on combined scores of activity and aggression (which are positively linked within individuals). Thus, apart from an active and aggressive strategy, there seems to be another more passive behavioral strategy.Electronic supplementary materialThe online version of this article (doi:10.1007/s00265-016-2215-y) contains supplementary material, which is available to authorized users.

Food restriction modifies ultrastructure of hippocampal synapses.

Consumption of high-energy diets may compromise health and may also impair cognition; these impairments have been linked to tasks that require hippocampal function. Conversely, food restriction has been shown to improve certain aspects of hippocampal function, including spatial memory and memory persistence. These diet-dependent functional changes raise the possibility that the synaptic structure underlying hippocampal function is also affected. To examine how short-term food restriction (FR) alters the synaptic structure of the hippocampus, we used quantitative electron microscopy to analyze the organization of neuropil in the CA1 stratum radiatum of the hippocampus in young rats, consequent to reduced food. While four weeks of FR did not modify the density, size, or shape of postsynaptic spines, the synapses established by these spines were altered, displaying increased mean length, and more frequent perforations of postsynaptic densities. That the number of perforated synapses (believed to be an indicator of synaptic enhancement) increased, and that the CA1 spine population had on average significantly longer PSDs suggests that synaptic efficacy of axospinous synapses also increased in the CA1. Taken together, our ultrastructural data reveal previously unrecognized structural changes at hippocampal synapses as a function of food restriction, supporting a link between metabolic balance and synaptic plasticity.

The Orphan G Protein-Coupled Receptor Gene GPR178 Is Evolutionary Conserved and Altered in Response to Acute Changes in Food Intake.

G protein-coupled receptors (GPCRs) are a class of integral membrane proteins mediating physiological functions fundamental for survival, including energy homeostasis. A few years ago, an amino acid sequence of a novel GPCR gene was identified and named GPR178. In this study, we provide new insights regarding the biological significance of Gpr178 protein, investigating its evolutionary history and tissue distribution as well as examining the relationship between its expression level and feeding status. Our phylogenetic analysis indicated that GPR178 is highly conserved among all animal species investigated, and that GPR178 is not a member of a protein family. Real-time PCR and in situ hybridization revealed wide expression of Gpr178 mRNA in both the brain and periphery, with high expression density in the hypothalamus and brainstem, areas involved in the regulation of food intake. Hence, changes in receptor expression were assessed following several feeding paradigms including starvation and overfeeding. Short-term starvation (12–48h) or food restriction resulted in upregulation of Gpr178 mRNA expression in the brainstem, hypothalamus and prefrontal cortex. Conversely, short-term (48h) exposure to sucrose or Intralipid solutions downregulated Gpr178 mRNA in the brainstem; long-term exposure (10 days) to a palatable high-fat and high-sugar diet resulted in a downregulation of Gpr178 in the amygdala but not in the hypothalamus. Our results indicate that hypothalamic Gpr178 gene expression is altered during acute exposure to starvation or acute exposure to palatable food. Changes in gene expression following palatable diet consumption suggest a possible involvement of Gpr178 in the complex mechanisms of feeding reward.

Short-term food restriction followed by controlled refeeding promotes gorging behavior, enhances fat deposition, and diminishes insulin sensitivity in mice

Rodents are commonly used in food restriction refeeding studies to investigate weight regain. Mice that are rationed food every 24h may consume all allocated food in a short time (gorge) and therefore undergo a brief well-fed period followed by an extended fasted period until the next day’s food allotment. These exaggerated metabolic states are not typical in mice fed ad libitum (nibbling). The aim of the current study was to elucidate the intraday and cumulative metabolic consequences of gorging (induced by food restriction) in mice during controlled refeeding. Accordingly, following a temporary food restriction, mice were fed rations similar to intakes of controls fed ad libitum. Temporary food restriction initiated gorging behavior that persisted during refeeding; consequently, metabolism-related measurements were obtained in the gorging mice during their daily fed and fasted metabolic states. Robust differences in adipose tissue lipogenic and inflammatory gene expression were found in the gorging mice by metabolic state (fed versus fasted). Additionally, despite a reduced cumulative food intake compared to mice fed ad libitum, restriction-induced gorging mice had increased intraabdominal fat accumulation, diminished hepatic and peripheral insulin sensitivity, and a gene expression profile favoring lipid deposition. Our findings highlight the intraday differences in gene expression in gorging mice before and after feeding that confound comparisons with mice fed ad libitum, or nibbling. The present study also provides evidence that weight regain following food restriction is associated with cumulative metabolic and behavioral abnormalities in mice.

Effect of food restriction on the energy metabolism of the Chinese bulbul (Pycnonotus sinensis).

Food resources play an important role in the regulation of animals' physiology and behavior. We investigated the effect of short-term food restriction on metabolic thermogenesis of Chinese bulbuls (Pycnonotus sinensis) by measuring changes in body mass, body fat, basic metabolic rate (BMR), and organ mass of wild-caught Chinese bulbuls from Wenzhou, China. Short-term food restriction induced a significant decrease in body mass and body fat but body mass returned to normal levels soon after food was no longer restricted. Food restriction caused a significant reduction in BMR after 7 days (P<0.05), which returned to normal levels after food restriction ceased. Log total BMR was positively correlated with log body mass (r(2)=0.126, P<0.05). The dry masses of livers and the digestive tract were higher in birds that had been subject to temporary food restriction than in control birds and those subject to continual food restriction (P<0.001 and P<0.05, respectively). There was also significant differences in the dry mass of the lungs (P<0.05), heart (P<0.01), and spleen (P<0.05) in birds subject to short-term food restriction compared to control birds and those subject to continual food restriction. BMR was positively correlated with body and organ (heart, kidney and stomach) mass. These results suggest that the Chinese bulbul adjusts to restricted food availability by utilizing its energy reserves, lowering its BMR and changing the weight of various internal organs so as to balance total energy requirements. These may all be survival strategies that allow birds to cope with unpredictable variation in food abundance.

Impacts of short-term food restriction on immune development in altricial house sparrow nestlings.

Food limitation is a common ecological scenario for nestling altricial birds, and reductions in growth and maintenance have been observed in resource-limited nestlings. Substantial development of the immune system occurs during the nestling period, yet the resource dependence of this immune development is understudied. We examined constitutive immune system development as well as acute-phase responses to lipopolysaccharide (LPS) injection after 48 h of food restriction in house sparrows at 7 and 13 d posthatch. We also examined nestlings that were restricted early (5-7 d) but refed and tested at 13 d posthatch to determine whether altered immune function and growth early in the nestling period were recovered upon return to adequate resource supply. Induced acute-phase protein response was reduced in food-restricted birds, yet no lasting reductions in acute-phase protein levels were observed in previously restricted nestlings that were challenged with LPS after refeeding. Food restriction did not significantly impact constitutive levels of complement-mediated lysis or circulating IgY antibodies. As a comparator to immune measures, we found that organ and tarsus size, as well as muscle size and citrate synthase enzyme activity (an index of muscle cellular aerobic capacity), were significantly reduced in food-restricted nestlings. Reductions in flight muscle mass and function persisted in birds refed after early food restriction, which may have contributed to persistent body temperature reductions observed in refed birds.

Pathophysiological Changes by Short-term Food Restriction in Obese Diabetic Rats

Aim: Reduced calorie intake by food restriction leads to extension of life span by exerting beneficial effects on metabolism. Zucker diabetic fatty (ZDF) rat is a type 2 diabetic model with obesity, showing the incidence of diabetes after 7 weeks of age. The present study investigated effects of 2-week food restriction on the pancreas in ZDF rats. Methods: ZDF rats were pair-fed with Zucker lean (ZL) rats from 7 to 9 weeks of age (The amount of food in ZDF rats was calculated based on the daily food consumption in ZL rats). Body weight and biochemical parameters such as serum glucose, triglyceride, total cholesterol, non-esterified fatty acid and insulin levels, were evaluated. After necropsy, islet size and insulin content in pancreas were measured. Original Research Article Miyajima et al.; BJMMR, 9(6): 1-7, 2015; Article no.BJMMR.18712 2 Results: The ZDF rats showed increased blood glucose, insulin and lipid levels at 7 weeks as compared with those in ZL rats. After food restriction for 2 weeks, the blood glucose, insulin, and triglyceride levels in pair-fed ZDF rats were decreased. The islet size in pair-fed ZDF rats decreased as compared with that in ad lib-fed ZDF rats, but the insulin content in pancreas of pairfed ZDF rats increased remarkably. Conclusion: ZDF rats showed improvement of pancreatic disorders by food restriction. Caloric restriction applied at an insulin resistant pre-diabetic stage is an effective means for preventing the pancreatic disorder in diabetes with obesity.

Behavioural Effects of Short-term Total Food Restriction in Rats

Abstract Reducing food intake can decrease anxiety indices in rats. Th e aim of this study was to evaluate the influence of short-term (48 hours) total food restriction on the behavioural characteristics, the motor coordination and balance, of rats. Th ree-month-old male Wistar albino rats (n=20) weighing 350-400 g were divided into a control group (food and water intake ad libitum) and an experimental group (total food restriction 48 hours before testing). Behavioural studies were performed using the open field, elevated plus maze, Barnes maze, beam walking, evoked beam walking and linear locomotor tests. Th e total distance moved, the velocity, the movement and the frequency in the centre zone of the open field were significantly higher in the treated group. Th e cumulative duration in the centre zone of the open field did not significantly increase in the treated group. Th e number of entries into the open arms, the total time spent in the open arms and the total distance moved in the elevated plus maze significantly increased with no change in the velocity in the food-restricted animals. Th e 48 hours of total food restriction did not affect the Barnes maze test parameters or the parameters of the linear locomotor test. Th e velocity recorded during the beam walking test was not affected by the food restriction, but the velocity recorded during the evoked beam walking test significantly decreased in the treated group. In summary, short-term total food restriction did not produce significant changes in the physical performance of rats but did result in anxiolytic- like behaviour accompanied by food-seeking behaviour due to enhanced motivation to forage for food.

Compensatory growth in nestling Zebra Finches impacts body composition but not adaptive immune function

ABSTRACT Compensatory strategies have evolved in birds to minimize the effects of poor rearing conditions on future survival and fitness. Undernourished nestlings may accelerate growth and/or development relative to age, termed compensatory growth, to achieve normal asymptotic size at the same time as well-fed chicks. While compensatory growth allows birds to fledge at a suitable size and time, it may have persistent detrimental effects on the development of complex body systems. Our study examined compensatory growth following short-term food restriction of caged groups of Zebra Finches (Taeniopygia guttata; adult breeding pair and their brood) during the nestling period, and tested for postrestriction effects on tissue maturity (indexed by body tissue water content) and adaptive immune function. Food restriction reduced nestling body mass, tarsus, and culmen growth. Rapid compensatory growth in body mass, but not in tarsus and culmen lengths, was observed upon return to ad libitum feeding of the food-re...

Behavioural effects of short-term total food restriction in rats

Reducing food intake can decrease anxiety indices in rats. Th e aim of this study was to evaluate the influence of short-term (48 hours) total food restriction on the behavioural characteristics, the motor coordination and balance, of rats. Th ree-month-old male Wistar albino rats (n=20) weighing 350-400 g were divided into a control group (food and water intake ad libitum) and an experimental group (total food restriction 48 hours before testing). Behavioural studies were performed using the open field, elevated plus maze, Barnes maze, beam walking, evoked beam walking and linear locomotor tests. Th e total distance moved, the velocity, the movement and the frequency in the centre zone of the open field were significantly higher in the treated group. Th e cumulative duration in the centre zone of the open field did not significantly increase in the treated group. Th e number of entries into the open arms, the total time spent in the open arms and the total distance moved in the elevated plus maze significantly increased with no change in the velocity in the food-restricted animals. Th e 48 hours of total food restriction did not affect the Barnes maze test parameters or the parameters of

Effect of short-term food restriction on iron metabolism, relative well-being and depression symptoms in healthy women.

AimThe idea that iron deficiency anemia can be recognized in depressive patients has been around for a few years, as well as negative association between ferritin levels and depression. Iron deficiency anemia, associated with low iron intake, has been observed in women using restriction diets, for example in vegetarians or anorexics. There are no data on the influence of the short-term food restrictions, observed for example in slimming women, on iron management and its connection with behavior expressed via changes in the subject’s emotional state.Materials and methodsThis study describes the effect of one- and two-day food restrictions (every 8 days for a period of 48 days) on selected iron management parameters in the serum and blood of 46 healthy volunteer women (23 in each group), aged 25.5 ± 3.0 years, in association with the subjects’ self-described emotional status and depression symptoms. The association between iron parameters and depression was also analyzed.ResultsResults show that short-term (2 days) fasting significantly decreases iron concentrations in serum and hair, as well as levels of ferritin, hemoglobin, hematocrit, red blood cells, and total iron binding capacity, but the short-term fasting did not influence the other iron management parameters. Each model of food restrictions also increased negative feelings towards depression. A significant negative correlation between serum ferritin levels and depression was found in women who starved for 2 days.ConclusionsThe study shows that, through an impact on mineral levels, even short-term food restrictions, as observed in many slimming women and girls, can be a reason for iron deficiency and also can alter the emotional status of healthy women. Maybe depression symptoms in anorexia or other eating disorders patients can be associated with iron deficiencies.

The Effect of Food Restriction on Appetite Regulating Hormones and Adiponectin Activity

We investigated the effects of short-term food restriction and repeated fasting and refeeding on appetite regulating hormones and adiponectin activity in rats. To investigate the acute and chronic effects of food restriction in vivo, Sprague-Dawley rats were divided into a control group (CON), a 1 day fasting group, a 2 days fasting gruop, a 3 days fasting gruop, a fasting and refeeding for 1 week gruoup and a fasting and refeeding for 2 weeks group. Blood glucose, triglyceride and total cholesterol decreased in all fasting groups compared to those in the CON group. Free fatty acid of all fasting groups was higher than those in the CON, and were lowest in the three cycle fasting and refeeding group. Blood insulin following short-term food restriction was lower than that in the CON. Blood ghrelin increased significantly (p ＜ 0.01) following the short-term food restriction, However, blood ghrelin in the repeated fasting and refeeding groups decreased significantly decreased (p ＜ 0.01) compared to that in the CON and short-term food restriction group. In contrast, blood leptin decreased significantly (p ＜ 0.01) in the short term food restriction group and the three cycle of fasting and refeeding group but increased in the six cycle of fasting and refeeding group. No significant differences in adiponectin contents were observed in the short-term food restriction group. But, adiponectin increased significantly (p ＜ 0.01) following the fasting and refeeding cycles. Blood adiponectin and blood leptin levels were showed positively correlated (r² = 0.469) when all samples were analysed together.

Effect of different levels of short-term feed intake on folliculogenesis and follicular fluid and plasma concentrations of lactate dehydrogenase, glucose, and hormones in Hu sheep during the luteal phase

This study investigated the effects of short-term food restriction or supplementation on folliculogenesis and plasma and intrafollicular metabolite and hormone concentrations. Ewes were randomly assigned to three groups: the control group received a maintenance diet (M) while the supplemented group and restricted group received 1.5×M and 0.5×M respectively on days 6-12 of their estrous cycle. Estrus was synchronized by intravaginal progestogen sponges for 12 days. On days 7-12, blood samples were taken. After slaughter, the ovarian follicles were classified and the follicular fluid was collected. Compared with restriction, supplementation shortened the estrous cycle length, decreased the number of follicles 2.5-3.5 mm and follicular fluid estradiol (E2) concentration, increased the number of follicles>3.5 mm and plasma glucose, insulin and glucagon concentrations, and augmented the volume of follicles>2.5 mm. Restricted ewes had higher intrafollicular insulin concentration, but it was similar to that of supplemented ewes. Compared with follicles≤2.5 mm, the intrafollicular glucose and E2 concentrations were increased and the testosterone, insulin, and glucagon concentrations and lactate dehydrogenase (LDH) activity were decreased in follicles>2.5 mm. Only in restricted ewes were intrafollicular LDH and testosterone concentrations in follicles≤2.5 mm not different from those in follicles≤2.5 mm. In conclusion, the mechanism by which short-term dietary restriction inhibits folliculogenesis may involve responses to intrafollicular increased E2, testosterone, and LDH levels in late-stage follicles. This may not be due to the variation of intrafollicular insulin level but rather due to decreased circulating levels of glucose, insulin, and glucagon.

Severe, short-term food restriction improves cardiac function following ischemia/reperfusion in perfused rat hearts

The purpose of this study was to clarify the characteristics of improved ischemic tolerance induced by severe, short-term food restriction in isolated, perfused rat hearts. Male Wistar (8 week-old) rats were given a food intake equivalent to a 70% reduction on the food intake of ad-libitum fed rats for 11 days (FR group and AL group, respectively). After this period, hearts were isolated and perfused in the Langendorff mode, and subjected to 20 min of global ischemia followed by 30 min of reperfusion. Although the coronary flow rate in the FR group (63.0 +/- 3.1 ml/min/g dry weight) was higher than that in the AL group (47.1 +/- 1.3 ml/min/g dry weight) during preischemic perfusion, the lactate release into the coronary effluent and absolute values of +dP/dt and -dP/dt in the FR group (2422 +/- 161 and -1282 +/- 51) were inversely lower than in the AL group (2971 +/- 156 and -1538 +/- 74, respectively). An increase in ischemic contracture was suppressed in the FR group. Following reperfusion, cardiac function, high-energy phosphate content, and intracellular pH, as measured by 31P-nuclear magnetic resonance spectroscopy, had recovered to a much greater degree in the FR group than in the AL group. The serum T3 level was significantly lower in the FR group (2.7 +/- 0.1 pg/ml) than in the AL group (3.6 +/- 0.1 pg/ml), and the levels of triglycerides, free fatty acids, insulin, and glucose were also significantly lower in the FR group than in the AL group. The protein expressions of myocyte enhancer factor 2A, Na(+), K(+)-ATPase, and phospholamban in the cardiac tissue were higher in the FR group than in the AL group. These results suggested that severe, short-term food restriction improves ischemic tolerance in rat hearts via altered expression of functional proteins induced by low serum T3 levels, decreased coronary conductance, and change in metabolic flux.

Attenuation of obesity by early-life food restriction in genetically hyperphagic male OLETF rats: Peripheral mechanisms

The alarming increase in childhood, adolescent and adult obesity has exposed the need for understanding early factors affecting obesity and for treatments that may help prevent or moderate its development. In the present study, we used the OLETF rat model of early-onset hyperphagia induced obesity, which become obese as a result of the absence of CCK 1 receptors, to examine the influence of partial food restriction on peripheral adiposity-related parameters during and after chronic and early short-term food restriction. Pair feeding (to the amount of food eaten by control, LETO rats) took place from weaning until postnatal day (PND) 45 ( early) or from weaning until PND90 ( chronic). We examined fat pad weight (brown, retroperitoneal, inguinal and epididymal); inguinal adipocyte size and number; and plasma leptin, oxytocin and creatinine levels. We also examined body weight, feeding efficiency and spontaneous intake after release from food-restriction. The results showed that chronic food restriction produced significant reductions in adiposity parameters, hormones and body weight, while early food restriction successfully reduced long-term body weight, intake and adiposity, without affecting plasma measurements. Early (and chronic) dieting produced promising long-term effects that may imply the reorganization of both peripheral and central mechanisms that determine energy balance and further support the theory suggesting that early interventions may effectively moderate obesity, even in the presence of a genetic tendency.

Critical periods of susceptibility to short-term energy challenge during pregnancy: Impact on fertility and offspring development

In female mammals, reproduction is tightly regulated by energy status and food availability. Although acute energetic challenges inhibit female reproductive behavior and gonadotropin secretion, less attention has been given to the effects of short-term energetic challenge on pregnancy and gestation. Furthermore, species differences in pregnancy physiology necessitate more detailed analyses of specific pregnancy models. Here, we studied musk shrews, which display induced ovulation and obligate delayed implantation, and whose reproductive physiology is tightly linked to metabolic status. We tested whether acute energetic challenges of varied degrees given at specific pregnancy stages (including before and after delayed implantation) have different effects on gestational outcome and offspring postnatal development. We found that 48 h of either 40% or 50% food restriction, which reduced body weight and strongly inhibited sexual behavior, had minimal effects on pregnancy success and litter dynamics when administered early in gestation (pre-implantation). However, < 30% of females experiencing short-term food restriction later in gestation successfully gave birth (versus ≥ 70% of ad-libitum fed controls), and the pups of these food-restricted females exhibited a 30% slower postnatal growth trajectory. Interestingly, although pregnancy success and litter dynamics were unaffected by food restriction before implantation, gestation length was increased by metabolic challenges experienced at this time, indicating that energy status may regulate the timing of implantation. We conclude that 1) there are critical periods of pregnancy, particularly after implantation, when short-term, mild energetic challenges have significant impacts on fertility and offspring postnatal development, and 2) delayed implantation may have evolved, in part, as a buffering mechanism to prevent pregnancy failure during impaired energy balance in early gestation.