Exogenous insulin enhances humoural immune responses in short-day,but not long-day,Siberian hamsters (Phodopus sungorus)

Many animals experience marked seasonal fluctuations in environmental conditions. In response, animals display adaptive alterations in physiology and behaviour, including seasonal changes in immune function. During winter, animals must reallocate finite energy stores from relatively costly, less exigent systems (e.g. reproduction and immunity) to systems critical for immediate survival (e.g. thermoregulation). Seasonal changes in immunity are probably mediated by neuroendocrine factors signalling current energetic state. One potential hormonal candidate is insulin, a metabolic hormone released in response to elevated blood glucose levels. The aim of the present study was to explore the potential role of insulin in signalling energy status to the immune system in a seasonally breeding animal, the Siberian hamster (Phodopus sungorus). Specifically, exogenous insulin was administered to male hamsters housed in either long ‘summer-like’ or short ‘winter-like’ days. Animals were then challenged with an innocuous antigen and immune responses were measured. Insulin treatment significantly enhanced humoural immune responses in short, but not long days. In addition, insulin treatment increased food intake and decreased blood glucose levels across photoperiodic treatments. Collectively, these data support the hypothesis that insulin acts as an endocrine signal integrating seasonal energetic changes and immune responses in seasonally breeding rodents.     

Photoperiod influences the critical caloric intake necessary to maintain reproduction among male deer mice (Peromyscus maniculatus).

The concept of critical day length is well established among rodents; reproductive function is maintained when day lengths are greater than some specific threshold. In addition to day length cues, seasonal breeding in deer mice can also be regulated by food availability. The caloric threshold necessary to support reproduction remains unspecified for seasonally breeding rodents. The present study examined the interaction between photoperiod and food availability on reproductive function in adult male deer mice (Peromyscus maniculatus). A critical caloric intake profile was constructed in long (16L:8D) and short (8L:16D) photoperiods; groups of deer mice in both photoperiods either received food ad libitum or 90, 80, or 70% of their individual ad libitum food intake for 10 wk. At autopsy, paired testes, epididymides, and seminal vesicles were removed and weighed. Body mass, total body fat, and total body water contents were also obtained. Short, as compared to long, day lengths inhibited the reproductive systems of male deer mice. However, food consumption interacted with photoperiod to affect reproductive function. Significant reductions in reproductive organ size as well as spermatogenic activity were observed among short-day mice after a 10% reduction in ad libitum food intake. Long-day animals required a 20% reduction in caloric intake to depress reproductive function. Body mass and total body water content were generally unaffected by either photoperiod or food consumption. Total body fat content was reduced in short- as compared to long-day mice. Individual reproductive responsiveness to short days increased as food availability decreased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reproductive activity influences thermoregulation and torpor in pouched mice, Saccostomus campestris

The Afrotropical pouched mouse Saccostomus campestris displays sexual disparity in the use of daily torpor; males reluctantly enter torpor. We tested the hypothesis that males may compensate for a limited heterothermic capacity with lower basal and resting metabolic rates relative to females. We also investigated the association between gonadal activity (testosterone) and the propensity for daily torpor. Body temperature and oxygen consumption were measured at various ambient temperatures and were compared between sexes under ad libitum and restricted-diet treatments. Whereas no significant sex differences were observed in body temperature and oxygen consumption under ad libitum treatment, there were pronounced differences in heterothermic responses under food restriction. Females employed torpor more frequently and also had lower minimum torpor body temperatures (ca. 25 degrees C) than males (ca. 29 degrees C). Testosterone inhibited torpor in males, whereas the majority of saline-treated animals employed torpor under both ad libitum and restricted-diet treatments. This study demonstrated that the limited capacity of male S. campestris to enter torpor is a consequence of reproductive activity and that opportunistic breeding and the absence of seasonal testes regression compromises the capacity to conserve energy through daily torpor.     

Spermatogenesis is modified by food intake in mice

Spermatogenesis is generally viewed as being resistant to reduced food intake in inbred strains of adult mammals. This consensus stems from studies that have failed to place testicular responses within the context of a species' reproductive characteristics. We exposed two species of wild rodents, house mice and deer mice, to a mild but sustained food restriction (30% reduction of ad libitum consumption for 5 weeks). Reproductive adjustments made by each species to inanition were strikingly different. Food restriction failed to modify spermatogenesis in house mice, but evoked a continuum of testicular responses in deer mice ranging from normal spermatogenesis to azoospermia. These findings have several novel implications: 1) modest food restriction evokes species-specific adjustments in testicular function, and 2) intraspecific variation in spermatogenesis suggests robust individual differences in sensitivity to alterations in food intake. Taken together, our findings underscore the importance of considering the effects of food intake on male reproduction within the framework of a species' physiological and evolutionary background.     

Effects of photoperiod and food availability on growth, leptin, sexual maturation and maintenance in the Mongolian gerbils (Meriones unguiculatus)

Reproductive activity of Mongolian gerbils is regulated by photoperiod nevertheless body weight regulation is controlled without ambient photoperiod. Food intake is a major factor affecting rodent reproductive efficiency. Leptin is a hormone secreted by adipose tissue and modulates food intake, energy expenditure and body fat stores. In this study we studied the interaction of photoperiod and food availability on growth, sexual maturation and leptin concentration in the male and female gerbils. Gerbils were gestated and reared in either 14L:10D or 2L:22D. At weaning, gerbils were housed individually and divided into three groups: fed ad libitum, fed 80% of ad libitum or fed 60% of ad libitum. Body weights were recorded at weaning and every week thereafter. After twelve weeks of treatment, animals were sacrificed and testes and uterine weights were determined and blood was collected for leptin measurement. Food restriction reduced body weight and inhibited reproductive development. Absolute paired testis weights were similar in ad lib and 80% of ad lib groups but significantly different compared with the 60% of ad lib group in both photoperiods. Body weights were also directly dependent upon the level of food restriction. Uterine mass was only affected in the 60% of ad lib group in 14L but both food restriction levels significantly affected the uterine weights in 2L. Significant variations were found in leptin profiles. Leptin concentration was highest in ad lib and 80% of ad lib groups and lowest in 60% of ad lib groups. These results suggest that the reproductive activity of Mongolian gerbils is sensitive to food intake and multiple potential environmental cues (e.g., food availability, temperature) can be utilized.     

Short day length enhances physiological resilience of the immune system against 2-deoxy-d-glucose-induced metabolic stress in a tropical seasonal breeder Funambulus pennanti

Studies demonstrate the importance of metabolic resources in the regulation of reproduction and immune functions in seasonal breeders. In this regard, the restricted energy availability can be considered as an environmental variable that may act as a seasonal stressor and can lead to compromised immune functions. The present study explored the effect of photoperiodic variation in the regulation of immune function under metabolic stress condition. The T-cell-dependent immune response in a tropical seasonal breeder Funambulus pennanti was studied following the inhibition of cellular glucose utilization with 2-deoxy-d-glucose (2-DG). 2-DG treatment resulted in the suppression of general (e.g., proliferative response of lymphocytes) and antigen-specific [anti-keyhole limpet hemocyanin IgG titer and delayed-type hypersensitivity response] T-cell responses with an activation of the hypothalamic–pituitary–adrenal axis, which was evident from the increased levels of plasma corticosterone. 2-DG administration increased the production of inflammatory cytokines [interleukin (IL)-1β and tumor necrosis factor (TNF)-α] and decreased the autocrine T-cell growth factor IL-2. The immunocompromising effect of 2-DG administration was retarded in animals exposed to short photoperiods compared with the control and long photoperiod-exposed groups. This finding suggested that short photoperiodic conditions enhanced the resilience of the immune system, possibly by diverting metabolic resources from the reproductive organs toward the immune system. In addition, melatonin may have facilitated the energy “trade-off” between reproductive and immune mechanisms, thereby providing an advantage to the seasonal breeders for their survival during stressful environmental conditions.     

Acute re-feeding reverses food restriction-induced hypothalamic-pituitary-gonadal axis deficits

Undernutrition has well-established effects on female reproduction. Here we describe the effects of food restriction on aspects of the hypothalamic-pituitary-gonadal (HPG) axis in the female musk shrew. We determined that acute re-feeding reverses deficits brought on by food restriction. Two days of food restriction led to an increase in proGnRH immunoreactive cells in the preoptic area relative to ad libitum-fed controls (AL). This increase was reversed by 90 min of ad libitum feeding in the re-fed females (RF). In addition, food-restricted (FR) females had significantly greater GnRH content in the median eminence than either the AL or RF females. After GnRH was administered, the majority of females in all food conditions ovulated, yet the FR females had significantly fewer corpora lutea than either the AL or RF animals. These data show that food restriction impairs HPG axis function in female musk shrews, and that some of these impairments can be rapidly reversed by acute re-feeding.     

Longevity-fertility trade-offs in the tephritid fruit fly, Anastrepha ludens, across dietary-restriction gradients

Although it is widely known that dietary restriction (DR) not only extends the longevity of a wide range of species but also reduces their reproductive output, the interrelationship of DR, longevity extension and reproduction is not well understood in any organism. Here we address the question: ‘Under what nutritional conditions do the longevity‐enhancing effects resulting from food restriction either counteract, complement or reinforce the mortality costs of reproduction? To answer this question we designed a fine‐grained DR study involving 4800 individuals of the tephritid fruit fly, Anastrepha ludens, in which we measured sex‐specific survival and daily reproduction in females in each of 20 different treatments (sugar : yeast ratios) plus 4 starvation controls. The database generated from this 3‐year study consisted of approximately 100 000 life‐days for each sex and 750 000 eggs distributed over the reproductive lives of 2400 females. The fertility and longevity‐extending responses were used to create contour maps (X‐Y grid) that show the demographic responses (Z‐axis) across dietary gradients that range from complete starvation to both ad libitum sugar‐only and ad libitum standard diet (3 : 1 sugar : yeast). The topographic perspectives reveal demographic equivalencies along nutritional gradients, differences in the graded responses of males and females, egg production costs that are sensitive to the interaction of food amounts and constituents, and orthogonal contours (equivalencies in longevity or reproduction) representing demographic thresholds related to both caloric content and sugar : yeast ratios. In general, the finding that lifespan and reproductive maxima occur at much different nutritional coordinates poses a major challenge for the use of food restriction (or a mimetic) in humans to improve health and extend longevity in humans.     

Neuropeptide Y influences acute food intake and energy status affects NPY immunoreactivity in the female musk shrew (Suncus murinus)

Neuropeptide Y (NPY) stimulates feeding, depresses sexual behavior, and its expression in the brain is modulated by energetic status. We examined the role of NPY in female musk shrews, a species with high energetic and reproductive demands; they store little fat, and small changes in energy can rapidly diminish or enhance sexual receptivity. Intracerebroventricular infusion of NPY enhanced acute food intake in shrews; however, NPY had little affect on sexual receptivity. The distribution of NPY immunoreactivity in the female musk shrew brain was unremarkable, but energy status differentially affected NPY immunoreactivity in several regions. Similar to what has been noted in other species, NPY immunoreactivity was less dense in brains of ad libitum shrews and greater in shrews subjected to food restriction. In two midbrain regions, both of which contain high levels of gonadotropin releasing hormone II (GnRH II), which has anorexigenic actions in shrews, NPY immunoreactivity was more sensitive to changes in food intake. In these regions, acute re-feeding (90-180 min) after food restriction reduced NPY immunoreactivity to levels noted in ad libitum shrews. We hypothesize that interactions between NPY and GnRH II maintain energy homeostasis and reproduction in the musk shrew.     

Body mass and behavior in Swiss mice subjected to continuous or discontinuous food restriction and refeeding

Food restriction (FR) is hypothesized to decrease body fat content of an animal and thus prevent obesity. However, the response of energy budget to a continuous (CFR) or discontinuous FR (DFR) remains inconsistent. In the present study, effects of CFR or DFR and refeeding on energy budget and behavior were examined in male Swiss mice. CFR significantly decreased the energy expenditure associated with basal metabolic rate (BMR) and activity behavior, but not sufficiently to compensate for energy deficit and thus resulted in lower body mass and fat content. DFR mice had a significantly higher food intake on ad libitum days and showed increases in BMR and activity after 4 weeks’ DFR, which might resulted in lower body mass and less body fat than controls. After being refed ad libitum, both CFR and DFR mice had similar body mass, BMR, and behavioral patterns to controls but had 95% and 75% higher fat content. This suggested that not only CFR but also DFR would be a significant factor in the process of obesity for animals that were refed ad libitum. It also indicated that food restriction interrupted many times by periods of ad libitum feeding had the same long-term effects like continuous underfeeding.     

Colony performance and immunocompetence of a social insect, Bombus terrestris, in poor and variable environments

1. Feeding and defence against parasites are among the major simultaneous requirements for survival and successful reproduction of any animal, including colonies of social insects. Harsh environments may therefore not only negatively affect overall success, but force animals to allocate resources in different ways, for example, to reduce immune defence under adverse conditions while maintaining growth rate.
2. This study examines how colony growth, reproduction and immune defence of the bumble bee, Bombus terrestris , varies with environmental condition. In particular, the manner in which limited or unpredictable food availability affects the number and size of workers and sexuals produced, the timing of reproduction, and the level of encapsulation of a novel antigen was tested. A new experimental paradigm was applied by splitting colonies into two halves while ensuring integrity by regular swaps of the residing queen.
3. The results show that limited food availability, as expected, led to fewer and smaller workers and sexuals. Unpredictable food availability, in contrast, was associated with higher numbers of workers and heavier sexuals. Also, reproductive success was highest under unpredictable conditions, due to an increased rate of collection of resources.
4. The timing of reproduction did not vary among treatments. Contrary to expectation, also immunocompetence did not vary among treatments.     

Reproductive energetics of the role reversing bushcricket,Kawanaphila nartee (Orthoptera: Tettigoniidae: Zaprochilinae)

Theory predicts that sexual differences in reproductive strategies arise because of differences in the magnitude of investment made by males and females in reproduction. In some bushcrickets, the typical sex role of competitive male and choosy female is reversed when populations are subject to nutrient stress. Here I present an energetic analysis of reproduction for the role reversing bushcricket, Kawanaphila nartee, that supports the contention that this sex role reversal is a consequence of reversal in the pattern of relative reproductive investment. When fed ad libitum, males spent 16% of their daily energy reserves on the spermatophore compared with 26% spent on calling to attract a mate. Females spent 29% of their daily energy reserves in producing and laying eggs. However, when allowed only limited access to food, female expenditure in eggs was reduced to 23% of daily reserves while male expenditure remained unchanged. After accounting for the incorporation of male nutrients into eggs, female energy expenditure in reproduction exceeded male expenditure when animals were fed ad libitum, but male expenditure exceeded female expenditure when diet was limited. This role reversal in relative energy expenditure that is associated with courtship role reversal supports classical and contemporary theories on the control of sexual selection.     

The glutamate agonist NMDA blocks gonadal regression and enhances antibody response to an immune challenge in Siberian hamsters (Phodopus sungorus)

Seasonal variation in behavior and physiology, including changes in immune function, are common. This variability is elicited by changes in photoperiod and often covaries with fluctuations in both energy reserves and reproductive state. It is unclear, however, whether changes in either variable alone drive seasonal changes in immunity. We investigated the relative contributions of reproduction and energy balance to changes in immune function. To accomplish this, we uncoupled seasonal changes in reproduction from those related to energy balance via daily injections of N-methyl-d-aspartate (NMDA) in Siberian hamsters (Phodopus sungorus). NMDA is a glutamatergic agonist that blocks short day-induced gonadal regression, while leaving short-day declines in body mass unaffected. In Experiment 1, we examined the effect of differing doses of NMDA on testosterone production as a proxy for NMDA effects on reproduction; a dose-dependent rise in testosterone was observed. In Experiment 2, animals were maintained on long or short days and received daily injections of NMDA. After 8 weeks, all animals underwent a humoral immune challenge. Short-day animals receiving daily injections of NMDA maintained long day-like gonads; however, contrary to our predictions, no trade-off between reproduction or energy balance and immune function was observed. Unexpectedly, NMDA treatment increased immunoglobulin levels in all groups, suggesting that NMDA may provide an immunomodulatory signal, presumably through actions on peripheral glutamate receptors. These results support a previous finding that NMDA blocks reproductive regression. In addition, these findings demonstrate a general immunoenhancing effect of NMDA that appears independent of changes in reproductive or energetic state of the animal.     

Food supplementation and testosterone interact to influence reproductive behavior and immune function in Sceloporus graciosus

The energetic resources in an organism's environment are essential for executing a wide range of life-history functions, including immunity and reproduction. Most energetic budgets, however, are limited, which can lead to trade-offs among competing functions. Increasing reproductive effort tends to decrease immunity in many cases, and increasing total energy via supplemental feedings can eliminate this effect. Testosterone (T), an important regulator of reproduction, and food availability are thus both potential factors regulating life-history processes, yet they are often tested in isolation of each other. In this study, we considered the effect of both food availability and elevated T on immune function and reproductive behavior in sagebrush lizards, Sceloporus graciosus, to assess how T and energy availability affect these trade-offs. We experimentally manipulated diet (via supplemental feedings) and T (via dermal patches) in males from a natural population. We determined innate immune response by calculating the bacterial killing capability of collected plasma exposed to Escherichia coli ex vivo. We measured reproductive behavior by counting the number of courtship displays produced in a 20-min sampling period. We observed an interactive effect of food availability and T-patch on immune function, with food supplementation increasing immunity in T-patch lizards. Additionally, T increased courtship displays in control food lizards. Lizards with supplemental food had higher circulating T than controls. Collectively, this study shows that the energetic state of the animal plays a critical role in modulating the interactions among T, behavior and immunity in sagebrush lizards and likely other species.     

The effect of duration and time of food availability on the photoperiodic response in the male house sparrow, Passer domesticus

We investigated the effects of food availability on the seasonal testicular growth in the photoperiodic house sparrow (Passer domesticus). Two experiments were performed, each lasting 4 weeks. In experiment 1, sparrows were exposed to natural (NDL; group 1), short (8L:16D; group 2) and long (16L:8D; groups 3-5) day lengths with access to food ad libitum (groups 1-3) or for 10 h (zeitgeber time (zt) 0-10, group 4; zt 0 is the time of light onset) or for 8 h (zt 8-16, group 5). Testes recrudesced under long, but not short and natural, day lengths, and the recrudescence under long days was influenced by the duration of food availability. In experiment 2, the sparrows were exposed to short (8L:16D, group 1) and long (16L:8D, groups 2-5) day lengths with access to food ad libitum (for groups 1 and 2) or for 6 h (for groups 3-5) at different times during the 16 h light period (group 3- zt 0-6, group 4- zt 5-11, group 5- zt 10-16). As the expected, the testes recrudesced only under long lengths, but the photoinduction was variable among the 4 groups. The testes grew to full size in groups 2 and 3 that received food either ad libitum or for 6 h at zt 0-6, but to sub-maximal size in the groups that received 6 h food either at zt 5-11 (group 4) or at zt 10-16 (group 5). Altogether, these results support the idea that the photoperiodic regulation of reproduction in a seasonally breeding species is influenced both by the duration and the time of food availability.     

Effects of feeding time constraints on body mass regulation and energy expenditure in wintering dunlin (Calidris alpina)

We examined the effects of time-restricted feeding on regulationof body mass and activity energy expenditure in captive winteringdunlin (Calidris alpina) held in outdoor aviaries at TomalesBay, California. In the first of two experiments, we comparedbirds under 24 h : 24 h (fasting : ad libitum feeding) foodrestriction with controls under continuous ad libitum feeding. In the second experiment, we compared birds under 24 h : 6 h: 12 h : 6 h (fasting : ad libitum : fasting : ad libitum)food restriction with birds under 24 h : 24 h food restriction.We estimated total energy expended on activities from dailymass balance using an additive model based on measures of grossenergy intake, thermoregulation, basal metabolism, and a sensitivity analysis of gross utilization efficiency and energy densityof reserve body tissue. Dunlin under 24 h : 24 h food restrictionovercompensated for body mass lost while fasting, increasingtheir body mass relative to controls fed ad libitum. Dunlinunder 24 h : 6 h : 12 h : 6 h food restriction were unable to recover body mass lost during the first fasting day. Whenallowed to feed, food-restricted birds reduced the amount ofenergy spent on being active and increased food intake andenergy storage relative to controls, but when forced to fast,they increased their activity energy expenditure. These patterns suggest winter body mass regulation consistent with the behaviorsof free-living dunlin in winter.     

Effects of chronic food restriction and treatments with leptin or ghrelin on different reproductive parameters of male rats

The existence of a close relationship between energy status and reproductive function is well-documented, especially in females, but its underlying mechanisms remain to be fully unfolded. This study aimed to examine the effects of restriction of daily calorie intake, as well as chronic treatments with the metabolic hormones leptin and ghrelin, on the secretion of different reproductive hormones, namely pituitary gonadotropins and prolactin, as well as testosterone, in male rats. Restriction (50%) in daily food intake for 20 days significantly reduced body weight as well as plasma PRL and T levels, without affecting basal LH and FSH concentrations and testicular weight. Chronic administration of leptin to rats fed ad libitum increased plasma PRL levels and decreased circulating T, while it did not alter other hormonal parameters under analysis. In contrast, in rats subjected to 50% calorie restriction, leptin administration increased plasma T levels and reduced testis weight. Conversely, ghrelin failed to induce major hormonal changes but tended to increase testicular weight in fed animals, while repeated ghrelin injections in food-restricted males dramatically decreased plasma LH and T concentrations and reduced testis weight. In sum, we document herein the isolated and combined effects of metabolic stress (50% food restriction) and leptin or ghrelin treatments on several reproductive hormones in adult male rats. Overall, our results further stress the impact and complex way of action of different metabolic cues, such as energy status and key hormones, in reproductive function also in the male.     

Melatonin mediates seasonal adjustments in immune function.

In addition to seasonal changes in reproductive function, seasonal changes in immune function are mediated by the pineal hormone, melatonin. Melatonin affects immune function both indirectly, acting through other hormones, and directly by acting on components of the immune system. Melatonin also affects tumorigenesis and tumor development. We hypothesize that many of the indirect effects of melatonin on immune function are mediated through glucocorticoids, and appear to be part of an integrated series of adaptations to manage energy. Direct effects of melatonin on immune function appear to be mediated by melatonin receptors on lymphatic tissue or on immune cells in circulation. Winter is energetically demanding and stressful; thermoregulatory demands typically increase when food availability decreases. Individuals would enjoy a survival advantage if seasonally recurring stressors could be anticipated and countered by bolstering immune function. To summarize, melatonin may be part of an integrative system to coordinate reproductive, immunologic and other physiological processes to cope successfully with energetic stressors during winter.     

Cue hierarchies and testicular development: is food a more potent stimulus than day length in an opportunistic breeder (Taeniopygia g. guttata)?

Opportunistic breeders inhabit areas with unpredictable changes in environmental conditions. In such places favorable breeding conditions can occur during any time of year, and one prediction is that individuals should attend to photoperiod less than to more immediate cues to time reproduction. This study tests whether zebra finches utilize photoperiod independently of other proximate cues, specifically food availability. We transferred semi-domesticated male Lesser Sundas zebra finches (Taeniopygia guttata guttata) from 8 h light, 16 h dark per day (8L:16D) with ad libitum food availability to 20L:4D with ad libitum food (LD ad lib group) or food restriction (LD restricted group). A third group remained on 8L:16D with ad libitum food availability (SD ad lib group). Testis volume in LD ad lib males increased and was larger than other groups within 30 and 60 days of photostimulation. By contrast, LD restricted males and SD ad lib males did not exhibit significant gonadal growth. However, both LD groups increased mass irrespective of food availability. Surprisingly, at the end of the experiment the SD ad lib group sang the most undirected song. Our data demonstrate that long days alone are not sufficient to drive reproductive development in this opportunistically breeding species. Rather, it appears that reproductive development is stimulated by extended feeding times or increased food abundance during long days, and not by changes in day length per se. These data lend support to the proposition that photoperiod acts as a supplementary cue or permissive factor in this system, and thus represents the possibility of a reversal in the hierarchy of cue sensitivity.     

Energy restriction restores the impaired immune response in overweight (cafeteria) rats

Impaired immune function linked to obesity has been shown in both human and animal studies. The purpose of this work was to evaluate the effects of a 4-week energy restriction (50% of total energy intake) on immune function in previously diet-induced (cafeteria) overweight rats. Flow cytometric analysis revealed that the number of spleen T helper cells were significantly (P < 0.05) elevated in control and overweight energy-restricted rats as compared with groups fed ad libitum groups. The proliferative response of splenocytes to phytohaemaglutinin and concanavalin A from overweight rats after energy restriction was significantly (P < 0.05) higher compared to overweight nonrestricted rats. The cytotoxic activity of natural killer cells tended to be lower in overweight rats compared to controls. Finally, control rats under the dietary deprivation period presented higher levels of uncoupling protein 2 mRNA and lower levels of leptin receptor mRNA compared with the reference control group. These results suggest that energy restriction is able to restore, at least in part, the impaired immune response commonly observed in overweight animals.