The role of insulin, corticosterone and other factors in the acute recovery of muscle protein synthesis on refeeding food-deprived rats.
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ABSTRACT:
SUBMITTER: Millward DJ
PROVIDER: S-EPMC1152549 | biostudies-other | 1983 Dec
REPOSITORIES: biostudies-other
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Project description:The effect of corticosterone on protein turnover in skeletal muscle was investigated in growing rats. Protein synthesis was measured in vivo by the constant infusion of [(14)C]tyrosine. The extent to which any effect of corticosterone is modulated by the hyperinsulinaemia induced by steroid treatment was examined by giving the hormone not only to adrenalectomized rats but also to streptozotocin-induced diabetic rats maintained throughout the treatment period on two dosages of insulin by an implanted osmotic minipump. Approximate rates of protein degradation were also estimated in some cases as the difference between synthesis and net change in muscle protein mass. Measurements were also made of free 3-methylhistidine concentration in muscle and plasma. At 10mg of corticosterone/100g body wt. per day, growth stopped and muscle wasting occurred, whereas at 5 mg of corticosterone/100g body wt. per day no net loss of protein occurred. However, this low dose did induce muscle wasting when insulin concentration was regulated by a dose of 1.2 units/day. Protein synthesis was markedly depressed in all treated groups, the depression in the insulin-maintained rats being marginally more than in the hyperinsulinaemic adrenalectomized rats. The oxidative soleus muscle appeared to be less susceptible to the effect of the corticosterone than was the more glycolytic plantaris or gastrocnemius muscle. Any effect of the corticosterone on protein degradation was much less than its effects on protein synthesis. Where increases in the degradation rates appeared to occur in the rats treated with 10mg of corticosterone/100g body wt. per day, the increases were less than 20%. The free intracellular 3-methylhistidine concentrations were doubled in all groups treated with 5 mg of corticosterone/100g body wt. per day and increased 5-fold in the adrenalectomized rats treated with 10mg of corticosterone/100g body wt. per day, with no change in plasma concentration in any of the groups. It is therefore concluded that: (a) the suppression of protein synthesis is the main effect of glucocorticoids in muscle; (b) marked increases in insulin afford only minor protection against this effect; (c) stimulation of protein degradation may occur, but to a much lesser extent.
| S-EPMC1158405 | biostudies-other
Project description:The effect of corticosterone treatment on the sensitivity of muscle protein synthesis to insulin infusion was assessed in post-absorptive young rats. To select the optimal time period for corticosterone treatment, protein synthesis was measured by injection of L-[2,6-3H]phenylalanine (1.5 mmol/kg body weight) 1, 4, 12 or 24 h after injection of corticosterone (5 mg/kg body wt.). Muscle protein synthesis was significantly decreased at 4 h and the effect was maximal by 12 h; liver protein synthesis was elevated at 12 h and 24 h. The dose-response of muscle protein synthesis to a 30 min infusion with 0-150 munits of insulin/h was then compared in rats pretreated with corticosterone (10 mg/100 g body wt.) or vehicle alone. When no insulin was infused, corticosterone inhibited protein synthesis in gastrocnemius muscle. High doses of insulin stimulated protein synthesis, but the inhibition by corticosterone was similar to that in the absence of insulin. At intermediate doses of insulin there was an increased requirement for insulin to elicit an equivalent response in muscle protein synthesis. Plantaris muscle responded in a manner similar to that of gastrocnemius, but neither soleus muscle nor liver responded significantly to insulin. These data suggest that corticosterone has two modes of action; one which is independent from and opposite to that of insulin, and a second which causes insulin-resistance through a decrease in sensitivity rather than a change in responsiveness.
| S-EPMC1149675 | biostudies-other
Project description:BackgroundRecovery growth is a phase of rapid growth that is triggered by adequate refeeding of animals following a period of weight loss caused by starvation. In this study, to obtain more information on the system-wide integration of recovery growth in muscle, we undertook a time-course analysis of transcript expression in trout subjected to a food deprivation-refeeding sequence. For this purpose complex targets produced from muscle of trout fasted for one month and from muscle of trout fasted for one month and then refed for 4, 7, 11 and 36 days were hybridized to cDNA microarrays containing 9023 clones.ResultsSignificance analysis of microarrays (SAM) and temporal expression profiling led to the segregation of differentially expressed genes into four major clusters. One cluster comprising 1020 genes with high expression in muscle from fasted animals included a large set of genes involved in protein catabolism. A second cluster that included approximately 550 genes with transient induction 4 to 11 days post-refeeding was dominated by genes involved in transcription, ribosomal biogenesis, translation, chaperone activity, mitochondrial production of ATP and cell division. A third cluster that contained 480 genes that were up-regulated 7 to 36 days post-refeeding was enriched with genes involved in reticulum and Golgi dynamics and with genes indicative of myofiber and muscle remodelling such as genes encoding sarcomeric proteins and matrix compounds. Finally, a fourth cluster of 200 genes overexpressed only in 36-day refed trout muscle contained genes with function in carbohydrate metabolism and lipid biosynthesis. Remarkably, among the genes induced were several transcriptional regulators which might be important for the gene-specific transcriptional adaptations that underlie muscle recovery.ConclusionOur study is the first demonstration of a coordinated expression of functionally related genes during muscle recovery growth. Furthermore, the generation of a useful database of novel genes associated with muscle recovery growth will allow further investigations on particular genes, pathways or cellular process involved in muscle growth and regeneration.
| S-EPMC2238769 | biostudies-literature
Project description:Limited resources result in competition among social animals. Nevertheless, social animals also have innate preferences for cooperative behavior. In the present study, 12 dyads of food-deprived rats were tested in four successive trials, and then re-tested as eight triads of food-deprived rats that were unfamiliar to each other. We found that the food-deprived dyads or triads of rats did not compete for the food available to them at regular spatially-marked locations that they had previously learnt. Rather, these rats traveled together to collect the baits. One rat, or two rats in some triads, lead (ran ahead) to collect most of the baits, but "leaders" differed across trials so that, on average, each rat ultimately collected similar amounts of baits. Regardless of which rat collected the baits, the rats traveled together with no substantial difference among them in terms of their total activity. We suggest that rats, which are a social species that has been found to display reciprocity, have evolved to travel and forage together and to share limited resources. Consequently, they displayed a sort of 'peace economy' that on average resulted in equal access to the baits across trials. For social animals, this type of dynamics is more relaxed, tolerant, and effective in the management of conflicts. Rather than competing for the limited available food, the food-deprived rats socialized and coexisted peacefully.
| S-EPMC5344391 | biostudies-literature
Project description:1. Insulin was infused into young male rats in the postabsorptive state. Rates of protein synthesis in skeletal muscle were determined during the final 10 min of infusion from the incorporation of label into protein after intravenous injection of a massive dose of [3H]phenylalanine. Rates of synthesis were not altered during the first 10 min of insulin infusion, but were increased significantly between 10 and 60 min. 2. Rats were infused with different amounts of insulin for 30 min. When concentrations were increased from 10 to 40 microunits/ml of plasma there was no change in muscle protein synthesis, but concentrations higher than 70 microunits/ml caused a significant stimulation. Concentrations below 10 microunits/ml, obtained by infusion of anti-insulin serum, did not depress synthesis below that found in the postabsorptive rat. 3. Infusion of glucose for 30 or 60 min led to an increase in plasma insulin to 40 microunits/ml, but this also failed to stimulate muscle protein synthesis. 4. Rates of synthesis in postabsorptive rats, even when stimulated maximally by insulin, were not so high as those in fed rats or in postabsorptive rats refed for 60 min. However, in fed and refed rats insulin concentrations were below that required to stimulate synthesis in postabsorptive animals. Despite this, infusion of large amounts of insulin into fed rats did not increase synthesis further. 5. The sensitivity of plasma glucose to insulin infusion was different from that of protein synthesis. A decrease in glucose concentration preceded the increase in synthesis and occurred at lower insulin concentrations. 6. It is concluded that changes in circulating insulin may have been partly responsible for the increase in muscle protein synthesis brought about by feeding, but that other factors must also play a part.
| S-EPMC1154276 | biostudies-other
Project description:ObjectiveObesity is a major cause of morbidity and mortality. Few weight-reducing medications are available, and these have limited efficacy. Cushing's Syndrome (caused by elevated glucocorticoid levels) and obesity have similar metabolic features. Though circulating glucocorticoid levels are not elevated in obesity, tissue-specific glucocorticoid levels have been implicated in the development of the metabolic phenotype of obesity. Tissue glucocorticoid levels are regulated by 11β-hydroxysteroid dehydrogenase type1 (11βHSD1), which increases the local concentration of active glucocorticoids by the production of corticosterone from 11-dehydrocorticosterone. 11βHSD1 is expressed in the hypothalamic arcuate nucleus (ARC), a major weight and appetite-regulating centre, and therefore represents a target for novel anti-obesity therapeutic agents. Thus, we sought to investigate the effect of chronic alterations of ARC corticosterone levels (mediated by 11βHSD1) on food intake and body weight in adult male rats.MethodsRecombinant adeno-associated virus particles bearing sense 11βHSD1 (rAAV-S11βHSD1) and small interfering 11βHSD1 (rAAV-si11βHSD1), respectively, were stereotactically injected into the ARC (bilaterally) of adult male Wistar rats. rAAV-GFP was injected into control groups of male Wistar rats. Food intake and body weight were measured three times a week for 70 days. Terminal brain, plasma and intrascapular brown adipose tissue (iBAT) samples were taken for measurement of mRNA expression and hormone levels.ResultsCompared to controls, rAAV-S11βHSD1 injection resulted in higher ARC corticosterone levels, hyperphagia and increased weight gain. Conversely, rAAV-si11βHSD1 injection (compared to controls) resulted in lower ARC corticosterone levels, higher iBAT uncoupling protein-1 mRNA expression and less weight gain despite similar food intake.ConclusionsTherefore ARC corticosterone, regulated by 11βHSD1, may play a role in food intake and body weight regulation. These data have important implications for the development of centrally-acting 11βHSD1 inhibitors, which are currently being developed for the treatment of obesity, metabolic disorders, and other conditions.
| S-EPMC7132090 | biostudies-literature
Project description:Food deprivation induces a repression of protein synthesis in skeletal muscle in part due to reduced signaling through the mammalian target of rapamycin complex 1 (mTORC1). Previous studies have identified upregulated expression of the protein Regulated in DNA Damage and Development (REDD1) as an important mechanism in the regulation of mTORC1 activity in response to a variety of stresses. Our goal in this investigation was to determine whether modulation of REDD1 expression occurs in response to food deprivation and refeeding, and, if it does, to ascertain if changes in REDD1 expression correlate with altered mTORC1 signaling. As expected, mTORC1 signaling was repressed after 18 h of food deprivation compared with freely-fed control rats and quickly recovered after refeeding for 45 min. Food deprivation caused a dramatic rise in REDD1 mRNA and protein expression; refeeding resulted in a reduction to baseline. Food deprivation is characterized by low-serum insulin and elevated glucocorticoid concentrations. Therefore, initially, alloxan-induced type I diabetes was used to minimize the food deprivation- and refeeding-induced changes in insulin. Although diabetic rats exhibited upregulated REDD1 expression compared with nondiabetic controls, there was no direct correlation between REDD1 mRNA expression and serum insulin levels, and insulin treatment of diabetic rats did not affect REDD1 expression. In contrast, serum corticosterone levels correlated directly with REDD1 mRNA expression (r = 0.68; P = 0.01). Moreover, inhibiting corticosterone-mediated signaling via administration of the glucocorticoid receptor antagonist RU486 blocked both the food deprivation- and diabetes-induced increase in REDD1 mRNA expression. Overall, the results demonstrate that changes in REDD1 expression likely contribute to the regulation of mTORC1 signaling during food deprivation and refeeding.
| S-EPMC2714387 | biostudies-literature
Project description:BackgroundInflammatory bowel disease (IBD) is a result of a complex interplay, making development of a specific treatment a challenging task. Corticosterone was considered a risk factor of stress relative enteritis. Our previous studies found that melatonin exerts an improvement effect in sleep deprivation (SD)- induced corticosterone overproduction and colitis. A present study further explored the mechanism whereby melatonin prevented corticosterone-mediated SD-induced colitis.MethodsA 72-hour SD mouse model with or without melatonin supplementation and fecal microbiota transplantation (FMT) to investigate the core role of corticosterone in melatonin-mediated gut microbiota improving SD-induced colitis. Further, corticosterone-treated mice were assessed to the effect of melatonin on corticosterone-mediated gut microbiota dysbiosis-induced colitis. Meanwhile, an in vitro test studied modulatory mechanism of metabolite melatonin.ResultsSD caused an excessive corticosterone, gut microbiota disorder and colitis phenotype. Similarly, corticosterone-supplemented mice also exhibited gut microbiota dysbiosis and colitis, and the FMT from SD-mice to normal mice could restore the SD-like colitis, but no change in the corticosterone level, which suggested that corticosterone-mediated intestinal microbiota imbalance plays a central role in SD-induced colitis. Further, we demonstrated melatonin-mediated MT2 weakened GR feedback, suppressed oxidative stress, restored the intestinal microbiota and its metabolites homeostasis, and inactivated the STAT3/AP-1/NF-κB pathway-induced inflammatory response in vivo and in vitro.ConclusionsWe revealed that excessive corticosterone is a core risk factor for SD-induced colitis and provided a better understanding of the effects of melatonin, expected to be a personalized targeted therapy drug, on corticosterone-mediated gut microbiota inducing colitis.
| S-EPMC8246302 | biostudies-literature
Project description:Corticosterone hormones mediate the stress response and function in the survival of hippocampal neurons via activation of gluco-(GR) and mineralocorticoid (MR) receptors. Activated GR and MR couple the corticosterone signal through immediate early genes (IEGs) to the late expression of downstream genes, such as neurotrophic factors. The potential importance of IEGs in GR/MR-dependent plasticity in the brain is largely unknown. We examined the region- and time-dependent transcriptional profiles of six IEGs (c-fos, fosB, fra-1, junB, c-jun and egr-1) by in situ hybridization after acute corticosterone challenge in the hippocampus and the primary somatosensory cortex (S1). Adrenalectomized rats and subsequent hormone injections were used as a model system to eliminate interference of endogenous corticosterone on IEG expression. In the hippocampus, a single corticosterone dose (10 mg/kg, s.c.) caused a widespread and transient reduction of fosB mRNA after 0.8 h, whereas changes in both c-fos and fra-1 mRNA levels were restricted to the dentate gyrus region. Corticosterone treatment gave rise to a delayed and significant reduction of junB mRNA signals after 2 h in all hippocampal regions, which reversed to increase at 4 h. c-jun and egr-1 mRNA levels were unaffected by corticosterone treatment. On the contrary, in the S1, IEG expression seems to be unaffected by corticosterone treatment, with the exception of a transient increase of junB transcripts at 0.8 h. The early reduction in c-fos family and junB transcripts may contribute to the GR/MR-dependent changes on hippocampal plasticity and may be dependent on rapid corticosteroid signaling.
| S-EPMC2435408 | biostudies-literature
Project description:Sleep deprivation (SD) leads to the spectrum of mood disorders like anxiety, cognitive dysfunctions and motor coordination impairment in many individuals. However, there is no effective pharmacological remedy to negate the effects of SD. The current study examined whether 50% ethanolic extract of Tinospora cordifolia (TCE) can attenuate these negative effects of SD. Three groups of adult Wistar female rats - (1) vehicle treated-sleep undisturbed (VUD), (2) vehicle treated-sleep deprived (VSD) and (3) TCE treated-sleep deprived (TSD) animals were tested behaviorally for cognitive functions, anxiety and motor coordination. TSD animals showed improved behavioral response in EPM and NOR tests for anxiety and cognitive functions, respectively as compared to VSD animals. TCE pretreatment modulated the stress induced-expression of plasticity markers PSA-NCAM, NCAM and GAP-43 along with proteins involved in the maintenance of LTP i.e., CamKII-α and calcineurin (CaN) in hippocampus and PC regions of the brain. Interestingly, contrary to VSD animals, TSD animals showed downregulated expression of inflammatory markers such as CD11b/c, MHC-1 and cytokines along with inhibition of apoptotic markers. This data suggests that TCE alone or in combination with other memory enhancing agents may help in managing sleep deprivation associated stress and improving cognitive functions.
| S-EPMC4857086 | biostudies-other