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Fasting-related hyperbilirubinemia in rats: the effect of decreased intestinal motility.

BACKGROUND & AIMS: Fasting increases serum bilirubin levels in both humans and rats. Because the pathogenesis of fasting hyperbilirubinemia is not fully understood, the effect of fasting on disposition of bile pigments was investigated in rats. METHODS: Bilirubin and urobilinogen were determined in excreta, bile, plasma, and liver tissues of fasted Gunn and Wistar rats. RESULTS: Fasting increased the intestinal transit time of Wistar rats. As a result, the fecal output of bile pigments was decreased by food deprivation. In contrast, the intestinal content of total bile pigments was augmented in both Wistar and Gunn rats. This finding was paralleled by the increase of serum bilirubin concentration in both rat strains. A similar increment of serum bilirubin levels was observed after injection of bilirubin into the cecum of Wistar rats. Furthermore, biliary efflux of bilirubin in Wistar rats was increased after 48 hours of fasting. Intubation of nonabsorbable bulk to fasted Wistar rats prevented the increase of serum bilirubin levels during a 48-hour period of food deprivation. CONCLUSIONS: Fasting decreases intestinal motility and elimination of bile pigments. Accumulation of bilirubin in the intestine during fasting allows enhanced enterohepatic circulation and results in an increased reflux to plasma. This seems to be a major factor involved in fasting-induced hyperbilirubinemia.

Analysis of Variance↗

The regulation of hepatic protein synthesis during fasting in the rat.

We have studied translational control in the model of 48 h of fasting in the rat. Our initial observations showed a paradoxical increase in ribosomal protein S6 (rpS6) phosphorylation and a decrease in eukaryotic initiation factor 2alpha (eIF2alpha) phosphorylation. These effects, which would favor an increase in protein synthesis, could be attributed to increased circulating concentrations of branched-chain amino acids in fasting. To determine what mechanisms might account for decreased hepatic translation in fasting, we examined the cap binding complex. eIF4E-bound 4E-BP1 did not increase. However, eIF4E-bound eIF4G and total cellular eIF4G were profoundly decreased in fasted liver. eIF4G mRNA levels were not lower after fasting. Based on the hypothesis that decreased eIF4G translation might account for the reduced eIF4G content, we fractionated ribosomes by sucrose density centrifugation. Immunoblotting for rpS6 showed modest polysomal disaggregation upon fasting. PCR analysis of polysome profiles revealed that a spectrum of mRNAs undergo different translational regulation in the fasted state. In particular, eIF4G was minimally affected by fasting. This indicated that reduced eIF4G abundance in fasting may be a function of its stability, whereas its recovery upon refeeding is necessarily independent of its own involvement in the cap binding complex. Western immunoblotting of polysome fractions showed that phosphorylated rpS6 was disproportionately present in translating polysomes in fed and fasted animals, consistent with a role in translational control. However, the translation of rpS8, an mRNA with a 5'-oligopyrimidine tract, did not coincide with rpS6 phosphorylation, thus dissociating rpS6 phosphorylation from the translational control of this subset of mRNAs.

Animals↗

Daily plasma citrate rhythms in man during feeding and fasting.

Daily plasma citrate rhythms were followed during a 24-h day in seven subjects fed a common diet and from 0800 to 2100 hours in : (1) ten subjects fed a citrate-poor diet; (2) eight subjects who continued overnight fasting (short-term fasting) and (3) nine obese patients during the 7th day of a total fasting (long-term fasting). During feeding plasma citrate increased after meals (from 9.0 to 30.7%). Citrate profiles did not change in subjects receiving the common and the citrate-poor diet. Plasma citrate rhythms correlated closely to rhythms of plasma lactate but not to rhythms of plasma glucose, free fatty acids (FFA) or insulin in feeding state. During short-term fasting, plasma citrate increased and remained high during long-term fasting as did plasma FFA concentration. Individual plasma concentrations of citrate and FFA correlated positively in the postabsorptive state. During long-term fasting same relation became negative, while individual concentrations of citrate and glucose correlated positively. Daily urinary citrate excretion over three sampling periods did not change during feeding, decreased during short-term fasting and was constantly low on the 7th day of fasting. The study demonstrates endogenous daily plasma citrate rhythms during feeding which vary as do plasma concentrations of carbohydrate metabolites. During fasting, an increased plasma citrate concentration is proposed as a more direct measurement of metabolic adaptations underlying the decreased glucose utilization than is an enhanced plasma FFA level.

Adult↗

The response of the hypothalamic-pituitary-gonadal axis to fasting is modulated by leptin.

Reproductive function is intimately related to caloric consumption. During fasting states, the hormones regulating reproduction, those of the hypothalamic-pituitary-gonadal axis, in particular, are severely altered. With the exciting observations that the obese (ob) gene product leptin, may also modulate neuroendocrine functions, we examined leptin's ability to prevent the consequences of fasting on reproductive hormones. Two groups of male rats, aged 65 days old, were either fasted and saline-injected or fasted and leptin-treated for approximately three days. Another group was given free access to rat chow. Leptin was able to prevent the fasting-induced fall of serum testosterone. Similar to testosterones dependence on leptin, leptin concentrations were somewhat dependent on testosterone. Castration accelerated the normal, age-related increase in serum leptin. Leptin also prevented the fasting-induced fall in luteinizing hormone (LH). The increase of beta-LH mRNA seen in the fasting state was prevented by leptin. There were no differences noted in luteinizing hormone releasing hormone (LHRH) mRNA among any of the groups. While neither fasting nor fasting plus leptin caused changes in serum prolactin, the increase in prolactin mRNA seen in fasted animals was prevented by leptin treatment. These data support the hypothesis that leptin plays a specific role in mediating the response of reproductive hormones to the nutritional status of the organism.

Analysis of Variance↗

Fasting hyperglycemia: etiology, diagnosis, and treatment.

Suboptimal glycemic control in individuals with type 1 and type 2 diabetes mellitus is associated with an increased risk of microvascular and macrovascular complications. Even brief periods of hyperglycemia increase the risk of complications. Fasting hyperglycemia is a phenomenon that has been observed in essentially all individuals with diabetes and may be due to dysregulation of the normal circadian hormonal patterns resulting in increased hepatic glucose output. Controlling hepatic glucose output and disposal is essential for effectively managing fasting hyperglycemia. Fasting hyperglycemia generally can be attributed to inadequate or inappropriate hepatic insulinization or the dawn phenomenon (fasting hyperglycemia occurring in the absence of antecedent hypoglycemia). Less commonly, the Somogyi effect (marked fasting hyperglycemia following antecedent hypoglycemia) can cause fasting hyperglycemia. Accurate diagnosis with overnight home blood glucose monitoring is important in developing an appropriate treatment strategy. Manipulation of the individual's diet or oral agent therapy may be all that is required in some individuals to reduce fasting hyperglycemia. Hepatic glucose output and disposal in the fasting state may be controlled via bedtime administration of either an intermediate-acting insulin such as NPH or a long-acting true basal insulin such as insulin glargine. Attention to fasting hyperglycemia coupled with appropriate individualization of treatment should improve the long-term outcome of individuals with type 1 and type 2 diabetes by reducing the risk of complications. Normalization of the fasting blood glucose, through whatever strategy, minimizes glucotoxicity and insulin resistance, profoundly influences daytime glycemic control, and profoundly reduces the risk of the complications of diabetes.

Circadian Rhythm↗

The effect of two periods of short-term fasting during the promotion stage of hepatocarcinogenesis in rats: the role of apoptosis and cell proliferation.

The loss of body and liver weight caused by chronic caloric restriction and its effects on carcinogenesis are well known; however, the effects of acute fasting on carcinogenesis have not been intensively investigated. We have studied some parameters of rat liver during short-term fasting and its effect on the stage of promotion in hepatocarcinogenesis in rats. During two fasting periods, body and liver weight decreased remarkably. Bromodeoxyuridine (BrdU) labeling indices (LI) decreased, and cell density increased prominently in liver sections. Hematoxylin and eosin-stained and nick end labeling (TUNEL)-stained sections showed an increase of apoptotic bodies in the absence of necrosis during the fasting period. Moreover, gel electrophoresis of DNA isolated from whole liver revealed ladder formation indicative of nucleosomal DNA cleavage. At the beginning of the fasting period livers exhibited a small but definite number of altered hepatic foci (AHF) expressing glutathione S-transferase, placental form (GST-P), but at the end of the fasting period no AHF were discernible in all livers of animals subjected to the fasting period. After refeeding, cell density and the incidence of apoptotic bodies decreased prior to a transient increase of BrdU LI. The percentage volume of liver occupied by AHF of fasted rats was significantly greater than that of control rats at 140 days after initiation. These results suggest that both the liver weight loss and the complete loss of discernible AHF from short-term fasting was caused by (i) decrease of cell volume, (ii) cell loss by apoptosis, and (iii) a decrease of hepatocyte proliferation. Furthermore, this relatively transient liver weight loss enhanced the promotion of hepatocarcinogenesis, possibly by enhanced cell proliferation compensatory to the fasting cycles.

Animals↗

Effect of short-term fasting on urinary excretion of primary lipid peroxidation products and on markers of oxidative DNA damage in healthy women.

The goal of this study was to determine whether short-term fasting changes in urinary biomarkers related to oxidative stress: malondialdehyde (MDA), 8-isoprostaglandin F2alpha (8-isoPGF), 8-hydroxydeoxy-guanosine (8-OHdG) and 1,N6-ethenodeoxyadenosine (epsilondA) among female volunteers participating in the short-term fasting program in South Korea. The study subjects were 52 healthy women (mean age 28, range 15-48 years old) who provided urine samples both before and after the fasting program (average 7.2, range: 3-11 days). Urinary MDA was measured by HPLC-UV and epsilondA levels were measured by immuno-affinity purification followed by HPLC-fluorescence detection. Urinary 8-OHdG and 8-isoPGF concentrations were determined by ELISA. Plasma leptin levels were also measured by radioimmunoassay. Information on demographic characteristics, personal habits (smoking and alcohol consumption) and previous medical history were collected by a self-administered questionnaire. Percent loss of body weight (average 6.3%, 4.28 +/- 0.25 kg) was significantly correlated with fasting duration (r = 0.70, n = 52, P < 0.01). The plasma leptin levels after fasting (5.89 +/- 1.10 ng/ml) were significantly lower than before fasting (6.91 +/- 1.13 ng/ml) (n = 27, P = 0.05). Urinary MDA levels after fasting (0.18 +/- 1.10 mg/g creatinine) were significantly lower than before fasting (0.37 +/- 1.11) (n = 51, P < 0.01). Urinary 8-isoPGF also were significantly reduced after fasting (n = 47, P < 0.01). However, there was no significant difference in 8-OHdG or epsilondA. There was a statistically significant correlation between % change of urinary MDA level with % change of 8-isoPGF level (partial correlation coefficient r = 0.57, n = 46, P = 0.01). The correlations between % change of 8-OHdG and plasma leptin was also significant (partial correlation coefficient r = 0.51, n = 27, P = 0.02). Our results demonstrate that the short-term fasting reduces lipid peroxidation products but does not affect oxidative stress-induced DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗

Fasting and diet affect the tolerance of young chickens exposed to acute heat stress.

The interaction of nutritional status on the tolerance of young chicks to acute heat stress (HS) was investigated. The results of experiment 1 demonstrated that fasting for 24, 48 or 72 hours progressively increased survival time (ST) of chicks exposed to HS. When compared to that of non-fasted (NF) chicks ST more than doubled for 48 and 72 hour fasted chicks. During HS plasma glucose increased in fasted chicks but decreased in NF chicks. Conversely, plasma free fatty acids decreased in fasted chicks and increased in NF chicks. Plasma phosphate of all chicks fell markedly as a result of HS. Chicks of experiment 2 were fed a "carbohydrate-free" diet (CF). Survival time of NF chicks fed CF was significantly greater than that of NF chicks fed a diet containing glucose. The apparent metabolic responses of NF chicks fed CF corresponded to those of fasted chicks of experiment 1. It was suggested that the metabolic substrate utilized by chicks during HS influences ST. The effect of CF diet on ST was also observed in chicks which were fasted for 48 hours prior to HS. Plasma phosphate of chicks exhibiting fasting metabolic responses was not significantly different at heat induced prostration despite marked differences in ST. The results of experiment 3 demonstrated that ST of fasted (24 hour) chicks previously fed a low phosphorus diet was markedly lower than compared to that of fasted chicks fed adequate dietary phosphorus. The effect of diet was found to be dependent on metabolic status since level of dietary phosphorus fed had no effect on ST of NF chicks. The results of the present study indicated that metabolic and nutritional status affect the tolerance of young chicks acutely exposed to high ambient temperature.

Animals↗

Effects of fasting on muscle protein turnover, the composition of weight loss, and energy balance of obese and nonobese Zucker rats.

The effects of prolonged fasting on the composition of weight loss and the rates of muscle protein synthesis and degradation were compared in obese and nonobese (lean) rats. Lean rats weighting 400 g could survive 60 days of fasting whereas obese rats weighing 550 g could survive 60 days. Weight loss was similar in both phenotypes over the first 10 days of fasting (15 g/day), but the composition of weight loss differed. Obese rats lost nearly twice as much lipid but only one-fifth as much body protein as lean rats. The fasting metabolic rate [kilocalories/(day . kilograms 0.75)] was similar in both phenotypes. This finding indicates a slower decline in metabolic rate during fasting in obese rats, since maintenance requirements are greater in lean rats. In fed rats, the fractional rates of muscle protein synthesis (FRS) and breakdown (FRB) were slightly higher in obese rats. Fasting reduced muscle protein synthesis in both phenotypes. In obese rats, however, the FRS declined more slowly than in lean rats. On the other hand, FRB decreased in fasted obese rats but greatly increased in fasted lean rats. It was concluded that the better protein retention and slower decline in metabolic rate in fasted obese rats were related to their different regulation of muscle protein synthesis and breakdown during fasting.

Animals↗

Preoperative fasting: old habits die hard.

OVERVIEW: Prolonged preoperative fasting is a time-honored tradition. The typical order of "npo after midnight" (or no liquid or food after 12 am on the day of surgery) has been challenged in recent years-so much so that in 1999 the American Society of Anesthesiology (ASA) revised its practice guidelines for preoperative fasting in healthy patients undergoing elective procedures. The newer, more liberal recommendations, based on studies showing that pulmonary aspiration occurs only rarely as a complication of modern anesthesia, allow the consumption of clear liquids up to two hours before elective surgery, a light breakfast (tea and toast, for example) six hours before the procedure, and a heavier meal eight hours beforehand. There is a well-known lag between the dissemination and implementation of practice guidelines, so the authors sought to determine whether the publication of the revised ASA recommendations had changed preoperative fasting practices. They interviewed 155 patients in one hospital about their preoperative fasting, comparing instructed, actual, and ASA-recommended fasting durations for liquids and solids. Their findings demonstrate that the majority of patients continued to receive instructions of npo after midnight for both liquids and solids, whether they were scheduled for early or late surgery. On average, the patients fasted from liquids and solids for 12 and 14 hours, respectively, with some patients fasting as long as 20 hours from liquids and 37 hours from solids. These fasts were significantly longer than those recommended by the ASA, indicating that inappropriate preoperative fasting is an issue that demands attention. The authors conclude that more collaboration between nurses and physicians is needed to assure that fasting instructions are consistent with the ASA guidelines and that patients understand these directives.

Adult↗

Prolonged pre-procedure fasting time is unnecessary when using titrated intravenous ketamine for paediatric procedural sedation.

BACKGROUND: Paediatric procedural sedation (PPS) is a common procedure in most general EDs. Many departmental guidelines suggest mandatory fasting times for children undergoing PPS, in an attempt to decrease the incidence of postoperative vomiting and (theoretically) aspiration pneumonitis, despite there being little or no evidence in the literature to support these mandatory fasting times. OBJECTIVES: To prospectively address the relationship between preprocedure fasting time and intraprocedure or postprocedure vomiting in children aged 1-12 years undergoing procedural sedation with intravenous ketamine in the ED. METHODS: From January 1999 to May 2000 all children presenting to the Royal Darwin Hospital Emergency Department with a condition requiring ketamine PPS were enrolled for data collection after parental consent was obtained. Titrated intravenous ketamine was administered via protocol. Prospective ED procedural sedation data collection forms of 272 consecutive cases of titrated intravenous ketamine sedation were reviewed. RESULTS: Fasting time was accurately recorded on 257 (95%) data collection forms. There was no intraprocedure vomiting. Overall rate of postprocedure vomiting was 13.9%. No statistically significant association between decreased fasting time and increased incidence of vomiting was found. In fact, there was a trend towards increased incidence of vomiting with increased fasting time (P = 0.08). The rate of vomiting of those children fasted 3 h or greater preprocedure (20/127 or 15.8%) was over twice the rate of those fasted less than 1 hour (2/30 or 6.6%). Incidence of vomiting was significantly associated with increasing age (P = 0.0007). No clinically evident aspiration pneumonitis occurred. CONCLUSION: Prolonged preprocedure fasting time did not reduce the incidence of postprocedure vomiting in this case series; to the contrary there was a increased incidence of vomiting with longer fasting times (P = 0.08). There was an increase in postprocedure vomiting with increasing age of the patients.

Age Distribution↗

Ghrelin induces fasted motor activity of the gastrointestinal tract in conscious fed rats.

Ghrelin is a newly discovered orexigenic peptide originating from the stomach. However, its action in regulating the fed and fasted motor activity of the digestive tract is not fully understood. In the present study, we examined the effects of intracerebroventricular (I.C.V.) and intravenous (I.V.) injection of ghrelin on the physiological fed and fasted motor activities in the stomach and duodenum of freely moving conscious rats. I.C.V. and I.V. injection of ghrelin induced fasted motor activity in the duodenum in normal fed rats, while I.V. injection of ghrelin induced fasted motor activity in both the stomach and duodenum in vagotomized rats. The effects of I.C.V. and I.V. injected ghrelin were blocked by growth hormone secretagogue receptor (GHS-R) antagonist given by the same route and also blocked by immunoneutralization of neuropeptide Y (NPY) in the brain. The effects of I.V. injected ghrelin were not altered by I.C.V. injection of GHS-R antagonist in vagotomized rats. Injection of GHS-R antagonist blocked the fasted motor activity in both the stomach and duodenum in vagotomized rats but did not affect the fasted motor activity in normal rats. Low intragastric pH inhibited the effect of ghrelin. The present results indicate that ghrelin is involved in regulation of fasted motor activity in the stomach and duodenum. Peripheral ghrelin may induce the fasted motor activity by activating the NPY neurons in the brain, probably through ghrelin receptors on vagal afferent neurons. Once the brain mechanism is eliminated by truncal vagotomy, ghrelin might be primarily involved in the regulation of fasted motor activity through ghrelin receptors on the stomach and duodenum. The action of ghrelin to induce fasted motor activity is strongly affected by intragastric pH; low pH inhibits the action.

Animals↗

Acetaminophen toxicity in fed and fasted mice.

Acetaminophen (750 mg/kg) toxicity and its modification by N-acetylcysteine (NAC, 1200 mg/kg) have been compared in fed and fasted mice. There was no significant difference between fed and fasted animals with respect to microsomal protein content, cytochrome(s) P-450 content, and aryl hydrocarbon hydroxylase activity. Glucuronyl transferase activity was significantly higher in fasted mice. Hepatotoxicity, as determined histologically and by liver enlargement was greater in fasted than fed mice. Covalent binding of [3H]acetaminophen metabolite(s) to liver proteins was also greater in fasted animals. NAC administration prevented acetaminophen-induced microscopic changes and liver enlargement and reduced the magnitude of covalent binding of acetaminophen metabolites. Fasting caused a marked fall in liver reduced sulfhydryl concentration. The incidence of acetaminophen-induced hypothermia was greater in fasted than in fed animals. NAC administration reduced hypothermia in fasted mice and abolished it in fed animals. It is concluded that enhanced acetaminophen toxicity in fasted mice compared with fed mice is unlikely to be a consequence of increased reactive metabolite formation, but rather a result of reduced inactivation of reactive metabolite(s) due to reduced hepatic glutathione stores in fasted mice.

Acetaminophen↗

The influence of renal nerves on electrolyte excretion in conscious and anesthetized rats fed or fasted overnight.

The role of the renal nerves in the electrolyte excretion of rats fed or fasted overnight was determined in conscious rats and anesthetized (Inactin) and surgically prepared rats. In conscious rats sodium excretion, as measured in a 1-h urine collection period after feeding or fasting overnight, was decreased with fasting with or without renal nerves. Renal nerve activity, as measured by norepinephrine turnover (inhibition of tyrosine hydroxylase by alpha-methyl-p-tyrosine), was not different between conscious fed or fasted rats and increased to the same extent in fed and fasted rats when anesthetized and surgically prepared. Anesthetized, surgically prepared rats infused with 5.0% glucose showed a denervation natriuresis if rats were fed overnight, but not if they had been fasted overnight. Potassium excretion in conscious and anesthetized rats was lower in fasted rats than fed rats with or without renal nerves. These data suggest (i) renal nerves are not involved in the renal response to an overnight fast in conscious rats, and (ii) in anesthetized, surgically prepared rat renal sympathetic tone is enhanced and denervation natriuresis occurs if rats are fed but not if fasted. Potassium excretion is a reflection of whether rats are fed or fasted and not whether they have renal nerves.

Anesthesia↗

Effects of fasting on serum lactogenic hormone concentrations during mid- and late pregnancy in mice.

Hormonal and metabolic responses to fasting were studied in pregnant Swiss Webster mice. Food was removed from pregnant mice 12, 24, 36, or 48 h before death on day 12 or 15 of pregnancy. Serum mouse placental lactogen-II (mPL-II), mouse growth hormone (mGH), mouse prolactin (mPRL), free fatty acids (FFA), and glucose concentrations were determined for each group. In comparing fasted animals with fed controls, there was a significant increase in the serum mPL-II concentration after 24 and 48 h of fasting on day 12 and after 12, 36, and 48 h of fasting on day 15. Fasting significantly decreased the glucose and increased the FFA concentration of the serum at all fasting periods. Fasting had no effect on serum mPRL or mGH concentrations. In the second part of this study, pregnant mice were fasted for 24 h and then refed for an additional 24 h before being killed on day 12 of pregnancy. The changes in serum mPL-II, glucose, and FFA concentrations that occurred after a 24-h fast on day 12 of pregnancy were completely reversed by refeeding the animals for 24 h. Results from both studies indicate the involvement of mPL-II in the maternal response to fasting in pregnant mice.

Animals↗

Plasma carnitine in fasting neonatal and adult northern elephant seals.

Maintenance of adequate body carnitine stores is a requisite for fasting mammals, whose energy is derived mainly from free fatty acid oxidation. The impact of longterm fasting on carnitine status is unclear, and there have been no reports of carnitine during naturally occurring fasts. Total (TC), free (FC), and acylated (AC) plasma carnitine levels were determined in 10 weaned and 11 adult northern elephant seals (Mirounga angustirostris) during natural fasts lasting from 1 to 3 mo. In pups, TC declined little and AC increased only slightly [P greater than 0.05, analysis of variance (ANOVA)] through 11 wk of fasting. Plasma FC dropped by 53 and 26% from week 1 values at 10 and 11 wk fasting, respectively (P = 0.014, ANOVA). The AC/FC ratio did not approach 1.0 until 7 wk of fasting. TC was 38.6 +/- 1.4 microM and 47.6 +/- 4.1 microM in adult females and males, respectively. Adult AC/FC ratios were 0.71 +/- 0.10 (females) and 0.08 +/- 0.04 (males). Plasma TC status is not negatively affected by extended fasting in adult and weaned northern elephant seals. These data support the hypothesis that fasting northern elephant seals defend plasma TC and maintain an attenuated AC/FC ratio well into their prolonged natural fast.

Acylation↗

NPY Y1 receptor is involved in ghrelin- and fasting-induced increases in foraging, food hoarding, and food intake.

Fasting triggers a constellation of physiological and behavioral changes, including increases in peripherally produced ghrelin and centrally produced hypothalamic neuropeptide Y (NPY). Refeeding stimulates food intake in most species; however, hamsters primarily increase foraging and food hoarding with smaller increases in food intake. Fasting-induced increases in foraging and food hoarding in Siberian hamsters are mimicked by peripheral ghrelin, central NPY, and NPY Y1 receptor agonist injections. Because fasting stimulates ghrelin and subsequently NPY synthesis/release, it may be that fasting-induced increased hoarding is mediated by NPY Y1 receptor activation. Therefore, we asked: Can an Y1 receptor antagonist block fasting- or ghrelin-induced increases in foraging, food hoarding, and food intake? This was accomplished by injecting the NPY Y1 receptor antagonist 1229U91 intracerebroventricularly in hamsters fasted, fed, or given peripheral ghrelin injections and housed in a running wheel-based food delivery foraging system coupled with simulated-burrow housing. Three foraging conditions were used: 1) no running wheel access, free food, 2) running wheel access, free food, or 3) foraging requirement (10 revolutions/pellet) for food. Fasting was a more potent stimulator of foraging and food hoarding than ghrelin. Concurrent injections of 1229U91 completely blocked fasting- and ghrelin-induced increased foraging and food intake and attenuated, but did not always completely block, fasting- and ghrelin-induced increases in food hoarding. Collectively, these data suggest that the NPY Y1 receptor is important for the effects of ghrelin- and fasting-induced increases in foraging and food intake, but other NPY receptors and/or other neurochemical systems are involved in increases in food hoarding.

Animals↗

Response of muscle protein synthesis to fasting in suckling and weaned rats.

Protein synthetic efficiency (KRNA) is low in immature skeletal muscle of suckling rats and increases toward the end of the suckling period. To determine whether immature skeletal muscle is able to further reduce KRNA in response to fasting, suckling (5, 10, and 16 days of age) and weaned (28 days of age) rats were fed, fasted for 10 h, or fasted for 18 h and injected with a flooding dose of L-[4-3H]phenylalanine for measurement of muscle protein synthesis in vivo. In fed rats, fractional rates of protein synthesis (KS) and protein synthetic capacity decreased during the suckling period. KRNA increased toward the end of the suckling period. In 5-day-old rats, fasting for 10 h produced a 50% decline in KS of extensor digitorum longus and plantaris muscles, but KS did not change further after 18 h of fasting. In older suckled and weaned rats, 10 h of fasting decreased KS of extensor digitorum longus and plantaris muscles 30%; after 18 h of fasting, values had declined to 50% of those in fed animals. The reductions in KS in soleus muscles with 10 and 18 h of fasting were similar to those in other muscles at 5 and 10 days but were less than those in other muscles at 16 and 28 days. Changes in KRNA were similar to those for KS in all muscles from all age groups fasted for 10 and 18 h. Protein synthetic capacity decreased approximately 12% after 18 h of fasting, but this effect did not differ between age groups or muscle types.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗