Effects Of Chronic Food Restriction Research Articles

Activation of Kappa Opioid Receptor Regulates the Hypothermic Response to Calorie Restriction and Limits Body Weight Loss.

Mammals maintain a nearly constant core body temperature (Tb) by balancing heat production and heat dissipation. This comes at a high metabolic cost that is sustainable if adequate calorie intake is maintained. When nutrients are scarce or experimentally reduced such as during calorie restriction (CR), endotherms can reduce energy expenditure by lowering Tb [1-6]. This adaptive response conserves energy, limiting the loss of body weight due to low calorie intake [7-10]. Here we show that this response is regulated by the kappa opioid receptor (KOR). CR is associated with increased hypothalamic levels of the endogenous opioid Leu-enkephalin, which is derived from the KOR agonist precursor dynorphin [11]. Pharmacological inhibition of KOR, but not of the delta or the mu opioid receptor subtypes, fully blocked CR-induced hypothermia and increased weight loss during CR independent of calorie intake. Similar results were seen with DIO mice subjected to CR. In contrast, inhibiting KOR did not change Tb in animals fed ad libitum (AL). Chemogenetic inhibition of KOR neurons in the hypothalamic preoptic area reduced the CR-induced hypothermia, whereas chemogenetic activation of prodynorphin-expressing neurons in the arcuate or the parabrachial nucleus lowered Tb. These data indicate that KOR signaling is a pivotal regulator of energy homeostasis and can affect body weight during dieting by modulating Tb and energy expenditure.

The role of the paraventricular nucleus of the thalamus in the augmentation of heroin seeking induced by chronic food restriction.

Drug addiction is a chronic disorder that is characterized by compulsive drug seeking and involves cycling between periods of compulsive drug use, abstinence, and relapse. In both human addicts and animal models of addiction, chronic food restriction has been shown to increase rates of relapse. Previously, our laboratory has demonstrated a robust increase in drug seeking following a period of withdrawal in chronically food-restricted rats compared with sated rats. To date, the neural mechanisms that mediate the effect of chronic food restriction on drug seeking have not been elucidated. However, the paraventricular nucleus of the thalamus (PVT) appears to be a promising target to investigate. The objective of the current study was to examine the role of the PVT in the augmentation of heroin seeking induced by chronic food restriction. Male Long-Evans rats were trained to self-administer heroin for 10days. Rats were then removed from the training chambers and experienced a 14-day withdrawal period with either unrestricted (sated) or mildly restricted (FDR) access to food. On day 14, rats underwent a 1-hour heroin-seeking test under extinction conditions, during which neural activity in the PVT was either inhibited or increased using pharmacological or chemogenetic approaches. Unexpectedly, inhibition of the PVT did not alter heroin seeking in food-restricted or sated rats, while enhancing neural activity in the PVT-attenuated heroin seeking in food-restricted rats. These results indicate that PVT activity can modulate heroin seeking induced by chronic food restriction.

Ad libitum feeding triggers puberty onset associated with increases in arcuate Kiss1 and Pdyn expression in growth-retarded rats.

Increasing evidence shows that puberty onset is largely dependent on body weight rather than chronological age. To investigate the mechanism involved in the energetic control of puberty onset, the present study examined effects of chronic food restriction during the prepubertal period and the resumption of ad libitum feeding for 24 and 48 h on estrous cyclicity, Kiss1 (kisspeptin gene), Tac3 (neurokinin B gene) and Pdyn (dynorphin A gene) expression in the hypothalamus, luteinizing hormone (LH) secretion and follicular development in female rats. When animals weighed 75 g, they were subjected to a restricted feeding to retard growth to 70–80 g by 49 days of age. Then, animals were subjected to ad libitum feeding or remained food-restricted. The growth-retarded rats did not show puberty onset associated with suppression of both Kiss1 and Pdyn expression in the arcuate nucleus (ARC). 24-h ad libitum feeding increased tonic LH secretion and the number of Graafian and non-Graafian tertiary follicles with an increase in the numbers of ARC Kiss1- and Pdyn-expressing cells. 48-h ad libitum feeding induced the vaginal proestrus and a surge-like LH increase with an increase in Kiss1-expressing cells in the anteroventral periventricular nucleus (AVPV). These results suggest that the negative energy balance causes pubertal failure with suppression of ARC Kiss1 and Pdyn expression and then subsequent gonadotropin secretion and ovarian function, while the positive energetic cues trigger puberty onset via an increase in ARC Kiss1 and Pdyn expression and thus gonadotropin secretion and follicular development in female rats.

SUN-LB273: Effects of Chronic Food Restriction and Sex on the Capacity of Gut Microbiota to Produce CLPB Protein: Putative Mechanisms Underlying Risk Factors of Eating Disorders

SUN-LB273: Effects of Chronic Food Restriction and Sex on the Capacity of Gut Microbiota to Produce CLPB Protein: Putative Mechanisms Underlying Risk Factors of Eating Disorders

Effect of chronic undernutrition on body mass and mechanical bone quality under normoxic and altitude hypoxic conditions.

Both undernutrition and hypoxia exert a negative influence on both growth pattern and bone mechanical properties in developing rats. The present study explored the effects of chronic food restriction on both variables in growing rats exposed to simulated high-altitude hypoxia. Male rats (n 80) aged 28 d were divided into normoxic (Nx) and hypoxic (Hx) groups. Hx rats were exposed to hypobaric air (380 mmHg) in decompression chambers. At T0, Nx and Hx rats were subdivided into four equal subgroups: normoxic control and hypoxic controls, and normoxic growth-restricted and hypoxic growth-restricted received 80 % of the amount of food consumed freely by their respective controls for a 4-week period. Half of these animals were studied at the end of this period (T4). The remaining rats in each group continued under the same environmental conditions, but food was offered ad libitum to explore the type of catch-up growth during 8 weeks. Structural bone properties (strength and stiffness) were evaluated in the right femur midshaft by the mechanical three-point bending test; geometric properties (length, cross-sectional area, cortical mass, bending cross-sectional moment of inertia) and intrinsic properties of the bone tissue (elastic modulus) were measured or derived from appropriate equations. Bone mineralisation was assessed by ash measurement of the left femur. These data indicate that the growth-retarded effects of diminished food intake, induced either by food restriction or hypoxia-related inhibition of appetite, generated the formation of corresponding smaller bones in which subnormal structural and geometric properties were observed. However, they seemed to be appropriate to the body mass of the animals and suggest, therefore, that the bones were not osteopenic. When food restriction was imposed in Hx rats, the combined effects of both variables were additive, inducing a further reduction of bone mass and bone load-carrying capacity. In all cases, the mechanical properties of the mineralised tissue were unaffected. This and the capacity of the treated bones to undergone complete catch-up growth with full restoration of the biomechanical properties suggest that undernutrition, under either Nx or Hx conditions, does not affect bone behaviour because it remains appropriate to its mechanical functions.

Fasting for weight loss: an effective strategy or latest dieting trend?

With the increasing obesity epidemic comes the search for effective dietary approaches for calorie restriction and weight loss. Here I examine whether fasting is the latest 'fad diet' as portrayed in popular media and discuss whether it is a safe and effective approach or whether it is an idiosyncratic diet trend that promotes short-term weight loss, with no concern for long-term weight maintenance. Fasting has long been used under historical and experimental conditions and has recently been popularised by 'intermittent fasting' or 'modified fasting' regimes, in which a very low-calorie allowance is allowed, on alternate days (ADF) or 2 days a week (5:2 diet), where 'normal' eating is resumed on non-diet days. It is a simple concept, which makes it easy to follow with no difficult calorie counting every other day. This approach does seem to promote weight loss, but is linked to hunger, which can be a limiting factor for maintaining food restriction. The potential health benefits of fasting can be related to both the acute food restriction and chronic influence of weight loss; the long-term effect of chronic food restriction in humans is not yet clear, but may be a potentially interesting future dietary strategy for longevity, particularly given the overweight epidemic. One approach does not fit all in the quest to achieve body weight control, but this could be a dietary strategy for consideration. With the obesity epidemic comes the search for dietary strategies to (i) prevent weight gain, (ii) promote weight loss and (iii) prevent weight regain. With over half of the population of the United Kingdom and other developed countries being collectively overweight or obese, there is considerable pressure to achieve these goals, from both a public health and a clinical perspective. Certainly not one dietary approach will solve these complex problems. Although there is some long-term success with gastric surgical options for morbid obesity, there is still a requirement for dietary approaches for weight management for the overweight and obese population, particularly as invasive interventions carry post-operative risk of death due to complications. Effective dietary interventions are required that promote long-term adherence and sustained beneficial effects on metabolic and disease markers. In general, such interventions need to be palatable and satiating, meet minimal nutritional requirements, promote loss of fat and preserve lean body mass, ensure long-term safety, be simple to administer and monitor and have widespread public health utility. Intermittent fasting or alternate day fasting may be an option for achieving weight loss and maintenance.

Are hungry sheep more pessimistic? The effects of food restriction on cognitive bias and the involvement of ghrelin in its regulation

Food restriction is considered to be a welfare issue in extensively reared animals. However, the effects of food restriction on the affective state, and its physiological regulation, are unknown. In Experiment 1, we aimed to assess the effects of increased plasma concentrations of acyl-ghrelin on judgement bias (an indicator of affective states) by fasting sheep for 24h or by ghrelin administration. In Experiment 2, we aimed to assess the effects of chronic food restriction on judgement bias and attention bias towards a food-related cue. For the judgement bias test, sheep were trained in an arena to approach a positive location cue associated with conspecifics and not approach a negative location cue associated with a dog. Three non-trained, non-reinforced ambiguous location cues were situated between the positive and negative locations. Attention bias towards a food-related cue was assessed by placing an empty food bucket against the wall of the arena halfway between the entry point and the positive location. In Experiment 1, sheep were divided into three treatments; 24h fast, ghrelin administration or control. Judgement bias, locomotor activity and plasma cortisol concentrations were assessed. The ghrelin treated group tended to express a more pessimistic bias compared to the control group (P<0.1), and plasma cortisol concentrations tended to be increased (P<0.1). In Experiment 2, sheep were subjected to a high feeding level (HF) or low feeding level (LF) for 7days. The LF group tended to show a more optimistic judgement bias (P<0.1). When the food-related cue was presented, LF ewes took longer to reach the positive location (P<0.001), spent longer with their head inside the bucket (P<0.001) and more time interacting with the bucket (P<0.01). This study provides preliminary evidence that food restriction alters judgement bias and attention bias towards a food-related cue which may indicate altered affective states of sheep.

The effects of chronic food restriction on cue-induced heroin seeking in abstinent male rats

Previous research with an animal model of relapse has shown that acute food deprivation will reinstate extinguished drug seeking. Recent evidence with humans, however, suggests that chronic food restriction rather than acute food deprivation is related to increases in drug taking and relapse, emphasizing a need for an animal model to elucidate the neural mechanisms mediating the effects of chronic food restriction on drug seeking. Here we studied the effects of chronic food restriction during a period of abstinence on heroin seeking in rats. Rats were trained to self-administer heroin over 10 days (0.1 mg/kg/infusion; i.v.). Rats were then removed from the operant conditioning chambers and exposed to a mild food restriction (resulting in 10-15 % decrease in body weight) or given unrestricted access to food for 14 days while abstinent. The abstinence period was followed by a drug-seeking test under extinction conditions. Subsequent experiments manipulated the length of restriction and test conditions. Rats that were food restricted throughout the abstinence period demonstrated a robust increase in cue-induced heroin seeking compared to sated rats. Re-feeding prior to testing or decreasing the length of the food restriction period prevented the augmentation of drug seeking. A combination of chronic food restriction and a concurrent state of hunger appears to be necessary for an increase in cue-induced heroin seeking following abstinence. The procedure presented here may serve as a useful model to study the increased risk for relapse following dietary manipulations in abstinent subjects.

Chronic restricted access to food leading to undernutrition affects rat neuroendocrine status and olfactory-driven behaviors

Previous studies have demonstrated that olfactory-driven behaviors in rats are influenced by short-term caloric restriction, partly through the modulation of olfactory sensitivity by appetite-modulating hormones or peptides such as insulin and leptin. Here, we addressed the issue of a long-term modulation of their neuroendocrine status by evaluating the effect of chronic food restriction in rats following a limitation of the duration of daily food intake to 2h (SF) instead of 8h (LF) on the expression of insulin and leptin system in the olfactory mucosa and bulb and on olfactory behaviors. This restriction resulted in a one-third reduction in the daily food intake and a 25% reduction in the body weight of SF rats when compared to controls, and was accompanied by lower levels of triglycerides, glucose, insulin and leptin in SF rats. Under these conditions, we observed a modulation of olfactory-mediated behaviors regarding food odors. In addition, restriction had a differential effect on the expression of insulin receptors, but not that of leptin receptors, in the olfactory mucosa, whereas no transcriptional change was observed at the upper level of the olfactory bulb. Overall, these data demonstrated that long-term changes in nutritional status modulate olfactory-mediated behaviors. Modulation of insulin system expression in the olfactory mucosa of food restricted rats suggests that this hormone could be part of this process.

Chronic food restriction up-regulates 11-β-hydroxysteroid dehydrogenase

Abstract Corticosterone — product of 11-β-hydroxysteroid dehydrogenase type I (11βHSD1) stimulates adipocytes differentiation and activates lipogenic enzymes gene expression in white adipose tissue (WAT) of rats. The aim of the study was to examine the effect of chronic food restriction, often practised by obese individuals trying to lose body mass, on: a) 11βHSD1 gene expression, b) expression of genes associated with adipocyte differentiation (PPARg, SREBP-1, adiponectin), and c) expression of genes associated with lipogenesis in WAT of rats. Two-month old rats were divided into a control and a food restricted group obtaining 50% of food consumed by controls for 30 days. mRNA levels of studied genes in perirenal WAT were analysed by real-time PCR. 11βHSD1 and lipogenic enzymes activities were measured by radiometric conversion assay and by spectrophotometric assay respectively. Food restriction caused significant increase of 11βHSD1, PPARg, SREBP1, adiponectin and lipogenic enzymes mRNA levels in perirenal WAT. 11βHSD1 and some lipogenic enzymes activities were also increased by food restriction. The coordinated up-regulation of 11βHSD1, and genes associated with adipocyte differentiation and lipogenesis by food restriction suggests that such nutritional condition shifts WAT metabolism, that would permit this tissue to synthesize and accumulate triacylglycerols immediately after refeeding.

The effect of chronic food restriction on immunopositive ACTH cells in peripubertal female rats

In peripubertal female rats, we have previously found that 50% food restriction (FR) increases plasma IL-6, haptoglobin and both alanine transaminase (ALT) and alkaline phosphatase (AST) aminotransferases, indicating the existence of an inflammatory response. To study whether such FR influences the hypothalamic-pituitary-adrenal (HPA) axis, we examined by immunohistochemistry the morphofunctional features of pituitary adrenocorticotroppic (ACTH) cells. In FR rats the volume and volume density of ACTH cells as well as plasma ACTH levels were increased by 17.6%, 12.5% and 13.4%, respectively, in comparison with controls (p<0.05). We concluded that chronic FR is a systemic stressor in young females, capable to stimulate the HPA axis, probably as a result of IL-6 action.

Up-regulation of stearoyl-CoA desaturase 1 and elongase 6 genes expression in rat lipogenic tissues by chronic food restriction and chronic food restriction/refeeding

Successful treatment of obesity and related diseases by chronic food restriction requires the understanding of the effect of such nutritional therapy on the expression of genes which have been implicated to be involved in some diseases associated with obesity. The purpose of this study was to examine the effect of chronic food restriction and chronic food restriction/refeeding on lipogenic enzymes, especially the expression of genes encoding the stearoyl-CoA desaturase 1 (Scd1) and elongase6 (Elovl6) in rat liver and adipose tissue. We found that both chronic food restriction and chronic food restriction/refeeding caused increased expression of the Scd1 and Elovl6 genes in both the liver and adipose tissue. The increase was more pronounced in case of chronic food restriction/refeeding (several-fold increase) than that in chronic food restriction alone (two to threefold increase). Essentially, similar results were obtained when the expression of fatty acid synthase, acetyl-CoA carboxylase, ATP-citrate lyase, and malic enzyme genes was studied. Moreover, we found that chronic food restriction and short-term fasting exert opposite effects on the expression of lipogenic enzymes genes. The increased expression of the genes encoding Scd1, Elovl6, and other key lipogenic enzymes may favor fat storage after chronic food restriction/refeeding and may be part of the molecular mechanism by which food restriction/refeeding increases body weight and enhances susceptibility to insulin resistance.

Central and peripheral effects of chronic food restriction and weight restoration in the rat

Previous studies have demonstrated that some endocrine consequences of long-term caloric restriction persist after weight restoration in human subjects. Here we evaluate effects of chronic food restriction in rats that were restricted to 70% of control kcal for 4 wk and subsequently weight restored. Measures were taken from rats at 80% (chronically restricted; CR), 90% (partially weight restored; PR), 100% (fully weight restored; FR), and after 4 wk at 100% body weight of controls (extended weight restored; ER). Plasma insulin and leptin were decreased, and ghrelin was increased in CR compared with controls. Leptin and ghrelin normalized with weight restoration at PR, FR, and ER; however, baseline insulin was not normalized until the ER state. Hypothalamic mRNA expression levels for proopiomelanocortin (POMC), agouti-related protein (AgRP), and neuropeptide Y (NPY) revealed significantly less POMC mRNA expression in CR and PR rats, and significantly less arcuate NPY mRNA in PR and FR. In the dorsomedial hypothalamus, CR, PR, and FR rats had significantly increased NPY expression that was not normalized until the ER state. In response to a test meal, insulin and ghrelin release patterns were altered through the FR stage, and ghrelin remained affected at ER. Collectively, these data demonstrate that mere weight restoration is not sufficient to normalize hypothalamic gene expression levels and endocrine responses to a meal, and that meal-related ghrelin responses persist despite weight restoration for up to 4 wk.

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.

Chronic food restriction and reduced dietary fat: Risk factors for bouts of overeating

The purpose of this study was to determine the effect of chronic food restriction and reduced dietary fat on feeding behavior and body weight. Young female rats were fed ad lib or food restricted on a low-fat (LF) or a fat-free (FF) diet for 4 weeks. Rats then received 24-h free access to 2 diets, the maintenance diet (LF or FF) plus a novel high-fat (HF) diet (24-h intake test). After the test, all the rats were allowed chronic free access to the HF diet until body weight was stable. During the 24-h test, the restricted groups ate significantly more calories than the ad lib groups, and the FF-restricted rats ate significantly more total food, carbohydrate and protein than the LF-restricted rats; there were no differences between the two ad lib groups. During chronic free access to the HF diet, the formerly restricted rats achieved and defended lower body weights than the formerly non-restricted rats. Throughout the experiment, the ad lib groups had more body fat than the restricted groups independent of the dietary subgroup. Hence, a history of chronic food restriction predisposes to consuming more food in acute feeding situations, particularly when dietary fat is reduced, and lowers the level of body weight maintained and defended. Chronic food restriction accompanied by reduced dietary fat may increase risk for bouts of overeating.

The effects of chronic food restriction on hypothalamic–pituitary–adrenal activity depend on morning versus evening availability of food

Partial food restriction (FR) protocols have been used not only to study behavioral and physiological consequences of decrease food intake, but as a necessary treatment of the animals in some operant learning tasks. It is well-established in rodents that restricting food availability to a few hours in the morning causes an alteration of the daily rhythm of corticosterone, thus making it difficult to evaluate whether or not such treatments are stressful. In the present experiment adult male Sprague–Dawley rats were subjected to two different FR schedules: food availability after 1100 h (LFR) or after 1900 h (DFR). After 14 days, animals from both groups, together with corresponding controls, were killed under resting conditions, either in the morning or in the evening, just before daily access to food in FR rats. Both FR schedules reduced body weight gain to the same extent, but their impact on the hypothalamic–pituitary–adrenal (HPA) axis was different: DFR increased relative, but not absolute, adrenal weight and morning and evening levels of corticosterone, whereas LFR increased both absolute and relative adrenal weights and increased morning corticosterone levels to a greater extent than DFR rats. Neither serum ACTH nor corticotropin-releasing factor (CRF) mRNA levels in the paraventricular nucleus of the hypothalamus were altered by DFR or LFR protocols, suggesting that factors other than CRF and ACTH are involved in the control of adrenocortical secretion under FR. It appears that LFR caused more alterations in the HPA axis than DFR and, therefore, the latter FR schedule should be used in those protocols necessarily involving partial FR.

MicroPET imaging in an animal model of anorexia nervosa

Anorexia nervosa is a life-threatening psychiatric disorder characterized by severe weight loss and high rates of comorbidity and mortality. The current study assessed the feasibility of using microPET imaging to study the effects of chronic food restriction in an animal model of anorexia nervosa. To establish preliminary support for this model, we hypothesized that chronic food restriction would decrease relative 2-deoxy-2-[18F]fluoro-D-glucose (18FDG) uptake in the rat, in effect modeling cerebral glucose hypometabolism reported in the clinical population of anorexia nervosa. Nine adolescent Wistar female rats received a baseline 18FDG scan. The control group received free access to food for a period of 25 days. The food restricted (FR) group received 40% of their baseline daily food intake until a 30% weight loss occurred; body weight was then maintained at 70% of baseline by adjusting daily food intake. The FR group also had free access to a running wheel for a mean period of 10.8+/-6.1 days. Both groups received a follow-up 18FDG scan. Relative 18FDG uptake was significantly increased in the cerebellum and significantly decreased in the hippocampus and striatum in the FR group compared to controls. Moreover, there was a trend towards a decrease in relative 18FDG uptake in the thalamus in the FR compared to control group. This is the first study to establish support for the use of microPET imaging in an animal model of anorexia nervosa as a means for studying the neurobiological changes that occur due to chronic food restriction.

Reduction of anxiety after restricted feeding in the rat: implication for eating disorders

Background Eating-disorder patients exhibit not only abnormal eating attitudes but also pathologic anxiety-like behaviors. The specific nature of the relationship between dieting and anxiety-like behavior is unknown. Methods To investigate the adaptational changes that resulted from chronic restricted scheduled feeding (2-hour access per day for 2 weeks) and subsequent free refeeding, longitudinal changes in the microstructure of feeding behavior were studied in male rats. To study the relationship between restricted feeding and anxiety-like behavior, separate rats were tested in the elevated plus-maze under the following conditions: 1) free feeding; 2) acute food restriction (2-hour access for 1 day); 3) chronic food restriction (for 10 days); or 4) postrecovery (after 10 days of free feeding subsequent to chronic food restriction). Results The effects of chronic food restriction on meal structure diminished within a few days after refeeding. Decreased anxiety-like behavior was seen during acute and chronic food restriction and did not reflect nonspecific behavioral activation. Anxiolytic-like effects persisted after 10 days of refeeding. Conclusions Chronic food restriction produced reductions in anxiety-like behavior that persisted beyond the normalization of food intake patterns. The findings might have etiologic and pathophysiologic relevance for the restrained eating pattern in eating-disorder patients with comorbid anxious symptoms.

The effect of chronic food restriction on liver acute phase protein response in female and male Wistar rats

The acute inflammatory response of the liver associated with chronic food restriction was examined in adult female and male Wistar rats. The changes in the levels of serum markers of liver injury, AST and ALT and the appearance of a serum marker of inflammation, the acute phase protein (APP) haptoglobin (Hp) were assessed following turpentine treatment of well-nourished (WN) controls and undernourished (UN) rats. Undernutrition was induced by food restriction during a six week period by offering chow equivalent to 50% of the normal food intake. In the female rats undernutrition significantly potentiated liver injury and increased their sensitivity to the toxic effects of turpentine, which was opposite to the results obtained for males. Differences in the basal levels of AST, ALT and Hp between females and males imply that the effects of chronic food restriction on protein synthesis in the liver are gender related.

Regional fat pad growth and cellularity in obese zucker rats: modulation by caloric restriction.

To investigate, in young obese male Zucker rats, the effects of chronic food restriction and subsequent refeeding on: 1). parameters of nonadipose and adipose growth, 2). regional adipose depot cellularity [fat cell volume (FCV) and number], and 3). circulating leptin levels. Obese (fa/fa) and lean (Fa/?) male Zucker rats were studied from age 5 to 19 weeks. After baseline food intake monitoring, 10 obese rats were subjected to 58 days of marked caloric restriction from ad libitum levels [obese-restricted (OR)], followed by a return to ad libitum feeding for 22 days. Ten lean control rats and 10 obese control rats were fed ad libitum for the entire experiment. All rats were fed using a computer-driven automated feeding system designed to mimic natural eating patterns. After food restriction, OR rats weighed significantly less than did lean and obese rats and showed a significant diminution in body and adipose growth as compared with obese rats. Relative adiposity was not different between obese and OR rats and was significantly higher than that of lean rats. The limitation in growth of the adipose tissue mass in OR rats was due mostly to suppression of fat cell proliferation because the mean FCV in each of the four depots was not affected. Serum leptin levels of OR and obese rats were not different from each other but were significantly higher than those of lean rats. Marked caloric restriction affects obese male Zucker rats in a manner different from that of nongenetic rodent models (i.e., Wistar rats). In comparison with the response to caloric deprivation of Wistar rats, these calorically restricted obese male Zucker rats appeared to defend their relative adiposity and mean FCV at the expense of fat cell number. These findings indicate that genetic and/or tissue-specific controls override the general consequences of food restriction in this genetic model of obesity.