Effect of excessive vitamin A intake on muscle protein turnover in the rat.
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ABSTRACT:
SUBMITTER: Hillgartner FB
PROVIDER: S-EPMC1158136 | biostudies-other | 1982 Feb
REPOSITORIES: biostudies-other
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Project description:Calvarial thinning and skull bone defects have been reported in infants with hypervitaminosis A. These findings have also been described in humans, mice and zebrafish with loss-of-function mutations in the enzyme CYP26B1 that degrades retinoic acid (RA), the active metabolite of vitamin A, indicating that these effects are indeed caused by too high levels of vitamin A and that evolutionary conserved mechanisms are involved. To explore these mechanisms, we have fed young mice excessive doses of vitamin A for one week and then analyzed the skull bones using micro computed tomography, histomorphometry, histology and immunohistochemistry. In addition, we have examined the effect of RA on gene expression in osteoblasts in vitro. Compared to a standard diet, a high dietary intake of vitamin A resulted in a rapid and significant reduction in calvarial bone density and suture diastasis. The bone formation rate was almost halved. There was also increased staining of tartrate resistant acid phosphatase in osteocytes and an increased perilacunar matrix area, indicating osteocytic osteolysis. Consistent with this, RA induced genes associated with bone degradation in osteoblasts in vitro. Moreover, and in contrast to other known bone resorption stimulators, vitamin A induced osteoclastic bone resorption on the endocranial surfaces.
| S-EPMC5398668 | biostudies-literature
Project description:Obstructive sleep apnoea (OSA) involves impaired upper airway muscle function and is linked to several pathologies including systemic hypertension, daytime somnolence and cognitive decline. Selenium is an essential micronutrient that exerts many of its effects through selenoproteins. Evidence indicates that either deficient or excessive dietary selenium intake can result in impaired muscle function, termed nutritional myopathy. To investigate the effects of selenium on an upper airway muscle, the sternohyoid, rats were fed on diets containing deficient, normal (0.5 ppm sodium selenite) or excessive (5 ppm selenite) selenium for a period of two weeks. Sternohyoid contractile function was assessed ex vivo. Serum selenium levels and activity of the glutathione antioxidant system were determined by biochemical assays. The abundance of three key muscle selenoproteins (selenoproteins -N, -S and -W (SELENON, SELENOS and SELENOW)) in sternohyoid muscle were quantified by immunoblotting. Levels of these selenoproteins were also compared between rats exposed to chronic intermittent hypoxia, a model of OSA, and sham treated animals. Although having no detectable effect on selected organ masses and whole-body weight, either selenium-deficient or -excessive diets severely impaired sternohyoid contractile function. These changes did not involve altered fibre size distribution. These dietary interventions resulted in corresponding changes in serum selenium concentrations but did not alter the activity of glutathione-dependent antioxidant systems in sternohyoid muscle. Excess dietary selenium increased the abundance of SELENOW protein in sternohyoid muscles but had no effect on SELENON or SELENOS. In contrast, chronic intermittent hypoxia increased SELENON, decreased SELENOW and had no significant effect on SELENOS in sternohyoid muscle. These findings indicate that two-week exposure to selenium-deficient or -excessive diets drastically impaired upper airway muscle function. In the sternohyoid, SELENON, SELENOS and SELENOW proteins show distinct alterations in level following exposure to different dietary selenium intakes, or to chronic intermittent hypoxia. Understanding how alterations in Se and selenoproteins impact sternohyoid muscle function has the potential to be translated into new therapies for prevention or treatment of OSA.
| S-EPMC11429047 | biostudies-literature
Project description:PurposeAcute bouts of resistance exercise and subsequent training alters protein turnover in skeletal muscle. The mechanisms responsible for the changes in basal post-absorptive protein turnover and its impact on muscle hypertrophy following resistance exercise training are unknown. Our goal was to determine whether post-absorptive muscle protein turnover following 12 weeks of resistance exercise training (RET) plays a role in muscle hypertrophy. In addition, we were interested in determining potential molecular mechanisms responsible for altering post-training muscle protein turnover.MethodsHealthy young men (n = 31) participated in supervised whole body progressive RET at 60-80% 1 repetition maximum (1-RM), 3 days/week for 3 months. Pre- and post-training vastus lateralis muscle biopsies and blood samples taken during an infusion of 13C6 and 15N phenylalanine and were used to assess skeletal muscle protein turnover in the post-absorptive state. Lean body mass (LBM), muscle strength (determined by dynamometry), vastus lateralis muscle thickness (MT), myofiber type-specific cross-sectional area (CSA), and mRNA were assessed pre- and post-RET.ResultsRET increased strength (12-40%), LBM (~5%), MT (~15%) and myofiber CSA (~20%) (p < 0.05). Muscle protein synthesis (MPS) increased 24% while muscle protein breakdown (MPB) decreased 21%, respectively. These changes in protein turnover resulted in an improved net muscle protein balance in the basal state following RET. Further, the change in basal MPS is positively associated (r = 0.555, p = 0.003) with the change in muscle thickness.ConclusionPost-absorptive muscle protein turnover is associated with muscle hypertrophy during resistance exercise training.
| S-EPMC5389914 | biostudies-literature
Project description:Skeletal muscle atrophy is associated with a disruption in protein turnover involving increased protein degradation and suppressed protein synthesis. Although it has been well studied that the IGF-1/PI3K/Akt pathway plays an essential role in the regulation of the protein turnover, molecule(s) that triggers the change in protein turnover still remains to be elucidated. TRB3 has been shown to inhibit Akt through direct binding. In this study, we hypothesized that TRB3 in mouse skeletal muscle negatively regulates protein turnover via the disruption of Akt and its downstream molecules. Muscle-specific TRB3 transgenic (TRB3TG) mice had decreased muscle mass and fiber size, resulting in impaired muscle function. We also found that protein synthesis rate and signaling molecules, mTOR and S6K1, were significantly reduced in TRB3TG mice, whereas the protein breakdown pathway was significantly activated. In contrast, TRB3 knockout mice showed increased muscle mass and had an increase in protein synthesis rate, but decreases in FoxOs, atrogin-1, and MuRF-1. These findings indicate that TRB3 regulates protein synthesis and breakdown via the Akt/mTOR/FoxO pathways.
| S-EPMC5675010 | biostudies-literature
Project description:The rate of synthesis and catabolism of sarcoplasmic- and myofibrillar-muscle protein was measured in operated, sham-operated and food-restricted rats by using Na2 14CO3. The food-restricted group underwent sham operations and were limited to the food intake of the operated animals. Protein synthesis and catabolism were increased in the sarcoplasmic-muscle fraction in operated rats compared with that in sham-operated or food-restricted rats. The rate of synthesis of the myofibrillar protein decreased in operated animals, but the rate of catabolism was not altered in the myofibrillar-muscle fraction of the operated animals compared with that in food-restricted and sham-operated animals. In the operated animals, there was a net loss of protein from the muscle. Thus the rats that underwent surgery lost muscle protein, primarily as a result of a decrease in synthesis of myofibrillar protein. The changes in protein turnover in operated animals were not due to decreases in food intake, since protein turnover in sham-operated animals that were restricted to the food intake of the operated rats was not different from that in sham-operated rats fed ad libitum.
| S-EPMC1186213 | biostudies-other
Project description:BackgroundWhile decreased protein intake is associated with muscle mass loss, it is unclear whether a decrease in carbohydrate intake adversely affects muscle atrophy independently of protein intake. Herein, we examined whether a low-carbohydrate (low-CHO) diet exacerbates denervation-induced muscle atrophy under conditions of identical protein intake.MethodsOn day one of the experiment, male Wistar rats underwent unilateral denervation. The contralateral leg was used as the control. After denervation, rats were divided into two dietary groups: high-carbohydrate (high-CHO) and low-CHO. Each group was fed a high-CHO (70% carbohydrate) or low-CHO (20% carbohydrate) diet over 7 days. Total protein and energy intakes in both groups were matched by pair feeding. Rats were provided with deuterium oxide (D2O) tracer over the last 3 days of dietary intervention to quantify myofibrillar (muscle) protein synthesis (MPS).ResultsDenervation reduced wet weight of the gastrocnemius muscle compared to the contralateral control (p < 0.05). Reductions in gastrocnemius muscle weight were greater in the low-CHO group (-34%) than the high-CHO group (-28%) (p < 0.05). Although denervation decreased MPS compared to the contralateral control (p < 0.05), no dietary effect on MPS was observed. Denervation resulted in increased mRNA and protein expression of Atrogin-1, a ubiquitin E3 ligase, compared to that in the contralateral control (p < 0.05). Increases in Atrogin-1 gene and protein expression due to denervation were greater in the low-CHO group than in the high-CHO group (p < 0.05).ConclusionsWe conclude that a low-CHO diet may exacerbate denervation-induced atrophy in fast-twitch-dominant muscles compared to a high-CHO diet, even when the same protein intake is maintained. Although blunted MPS contributed to muscle atrophy due to denervation, exacerbation of muscle atrophy by the low-CHO diet was not accompanied by explanatory changes in MPS. The effect of the low-CHO diet might be related to promotion of muscle-specific ubiquitin E3 ligase gene expression.
| S-EPMC11859665 | biostudies-literature
Project description:This cohort study aimed to identify the associations of dairy protein intake with the risk of developing a low muscle mass during a 12-year follow-up period, using data from 4412 middle-aged Korean Genome and Epidemiology Study participants with a normal baseline muscle mass. Dairy protein intake at baseline was assessed using a semi-quantitative Food Frequency Questionnaire. Skeletal muscle mass index (SMI), defined as the weight-adjusted skeletal muscle mass, was measured biennially using multi-frequency bioelectrical impedance analyses. Cox proportional hazards regression analysis was used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Overall, 395 subjects developed a low SMI (%) during an average follow-up of 141 (19-152) months. The average consumption of milk and other dairy products was 73.6 and 104.1 g/day, respectively. In men, a higher dairy protein intake was associated with a decreased risk of developing a low SMI (tertile 3 [T3] vs. T1, HR: 0.63; 95% CI: 0.42, 0.94; p for trend = 0.029). In a stratified analysis according to a total protein intake, this association was stronger in the lower-protein intake group (HR: 0.59; 95% CI: 0.35, 0.99; p for trend = 0.036) but not detected in the higher-protein intake group. Men who consumed milk ?1 time/day had a significantly lower risk of developing a low SMI (HR: 0.62; 95% CI: 0.39, 0.98; p for trend = 0.023). No significant associations were observed in women. In summary, dairy consumption appears to be beneficial for decreasing the risk of developing a low muscle mass in middle-aged Korean men.
| S-EPMC7551315 | biostudies-literature
Project description:To evaluate the impact of perinatal iodine excess intake on neurodevelopment, we conducted a gene expression profiling assessment using microarray technology. This evaluation was performed on the hippocampus of adult female offspring mice from both the 20-fold iodine intake group and the control group, which exhibited statistically significant differences in learning and memory-related behavioral experiments. Despite the observed behavioral differences, no significant differences were found in the gene expression profiles.
2025-06-01 | GSE270137 | GEO
Project description:The effects of denervation on muscle weight, rates of protein synthesis and breakdown, and RNA concentraitons were studied in the soleus and extensor digitorum longus muscle. Althrough the soleus underwent a true atrophy after section of the sciatic nerve, the extensor digitorum longus continued to grow, albeit at a lower rate than innervated controls. At 24h after nerve section protein breakdown was increased in both muscle types when compared with internal controls, and remained so throughout the 10 days studied. The possibility that this increased catabolism might arise from conformational changes of proteins after denervation was not substantiated, as myofibrillar or soluble proteins of denervated and control tissues were equally susceptible to degradation in vitro by three proteinases. Tyrosine uptake into the denervated extensor digitorum longus was decreased throughout the 10 days studied, whereas two phases of increased transport of the amino acid were found in the soleus. Significant decreases in rates of protein synthesis were found 1 and 2 days after denervation and results are presented that suggest that these changes may result from a decrease in ribosomal involvement in the translation process. These initial decreases were not maintained and the rate of protein synthesis was in fact increased when compared with controls, at 7 and 10 days. The increased synthetic rates of the 7-day denervated tissues were reflected as proportional increases in both myofibrillar and soluble proteins. It is suggested that the increase in synthesis at this time may result from an increase in both the abailability and active involvement of ribosomes, and that these anabolic trends may be caused by spontaneous fibrillation and/or the amount of passive stretching of the denervated muscles.
| S-EPMC1163718 | biostudies-other
Project description:Rates of growth and protein turnover in the breast muscle of young chicks were measured in order to assess the roles of protein synthesis and degradation in the regulation of muscle mass. Rates of protein synthesis were measured in vivo by injecting a massive dose of L-[1-14C]valine, and rates of protein degradation were estimated as the difference between the synthesis rate and the growth rate of muscle protein. In chicks fed on a control diet for up to 7 weeks of age, the fractional rate of synthesis decreased from 1 to 2 weeks of age and then changed insignificantly from 2 to 7 weeks of age, whereas DNA activity was constant for 1 to 7 weeks. When 4-week-old chicks were fed on a protein-free diet for 17 days, the total amount of breast-muscle protein synthesized and degraded per day and the amount of protein synthesized per unit of DNA decreased. Protein was lost owing to a greater decrease in the rate of protein synthesis, as a result of the loss of RNA and a lowered RNA activity. When depleted chicks were re-fed the control diet, rapid growth was achieved by a doubling of the fractional synthesis rate by 2 days. Initially, this was a result of increased RNA activity; by 5 days, the RNA/DNA ratio also increased. There was no evidence of a decrease in the fractional degradation rate during re-feeding. These results indicate that dietary-protein depletion and repletion cause changes in breast-muscle protein mass primarily through changes in the rate of protein synthesis.
| S-EPMC1162817 | biostudies-other