High-phosphorus diet maximizes and low-dose calcitriol attenuates skeletal muscle changes in long-term uremic rats

Acevedo, Luz M.; López, Ignacio; Peralta-Ramírez, Alan; Pineda, Carmen; Chamizo, Verónica; Rodríguez, Mariano; Aguilera–Tejero, Escolástico; Rivero, José‐Luis L.

doi:10.1152/japplphysiol.00957.2015

Cited by 15 publications

(20 citation statements)

References 52 publications

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“…However, phosphate excess is also toxic on skeletal muscle in the uremic rats. 6 These rats display slow-to-fast fiber-type transformation and increased muscle atrophy. 6 High Pi diet also induces ectopic skeletal muscle calcification in young mdx mice, a mouse model of muscular dystrophy with impairment in both cardiac and skeletal muscle function.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, up to 25% of US adults consume Pi at 3-4 fold higher than the recommended daily allowance on a regular basis. 5 Studies in uremic rats 6 and a mouse model of muscular dystrophy 7 have demonstrated skeletal muscle damage which was potentiated by dietary Pi excess. Recent studies from our group have also demonstrated that high Pi intake triggered augmented increases in sympathetic nervous system activity and blood pressure (BP) during muscle contraction in normal rats 8 .…”

Section: Introductionmentioning

confidence: 99%

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High-Phosphate Diet Induces Exercise Intolerance and Impairs Fatty Acid Metabolism in Mice

et al. 2019

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Background Inorganic phosphate (Pi) is used extensively as a preservative and a flavor enhancer in the Western diet. Physical inactivity, a common feature of Western societies, is associated with increased cardiovascular morbidity and mortality. It is unknown if dietary Pi excess contributes to exercise intolerance and physical inactivity. Methods We used multivariable linear regression (adjusted for age, sex, race, body mass index, systolic blood pressure, eGFR, fasting plasma glucose, and HDL cholesterol) to assess the relationship between serum Pi and actigraphy‐determined physical activity level as well as left ventricular function by cardiac magnetic resonance imaging in the Dallas Heart Study‐2 (DHS) participants. To determine direct effects of dietary Pi on exercise capacity, we measured oxygen uptake, serum non‐esterified fatty acid (NEFA) and glucose during exercise treadmill test and compared between C57/BL6 mice fed either a high Pi (2%) or normal Pi (0.6%) diet for 12 weeks. Skeletal muscle gene expression profiles for genes involved in fatty acid (FA) metabolism were compared between groups after 12 weeks of normal or high Pi diet. To further determine direct effect of Pi on muscle metabolism and expression of genes involved in FA metabolism, additional studies were conducted after subjecting differentiated C2C12 myotubes to media containing 1–3 mM Pi (pH 7.0) to simulate in vivo high phosphate conditions. Results In participants of the DHS (n = 1,603), higher serum Pi was independently associated with reduced time spent in moderate‐to‐vigorous physical activity (p = 0.01) and increased sedentary time (p = 0.004). There was no association between serum Pi and left ventricular ejection fraction or volumes. In animal studies, compared to control diet, consumption of high Pi diet for 12 weeks did not alter body weight or left ventricular function but reduced maximal oxygen uptake, treadmill duration, spontaneous locomotor activity, fat oxidation, fatty acid (FA) levels and led to downregulation of genes involved in FA synthesis, release, and oxidation, including Fabp4, Hsl, Fasn, and Pparg in muscle (p<0.05 for all). Similar results are recapitulated in vitro by incubating C2C12 myotubes with high Pi media. Conclusion Our data demonstrate a detrimental effect of dietary Pi excess on skeletal muscle FA metabolism and exercise capacity, which is independent of obesity and cardiac contractile function. Dietary Pi may represent a novel and modifiable target to reduce physical inactivity associated with the Western diet. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High-Phosphate Diet Induces Exercise Intolerance and Impairs Fatty Acid Metabolism in Mice

et al. 2019

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“…In a recent literature, Acevedo et al . demonstrated that high-phosphorus diet potentiated adverse skeletal muscle changes in long-term uremic rats 11 . Inorganic phosphate had been observed to play an important role in muscle contractile function 12 , and increased inorganic phosphate was involved in skeletal muscle fatigue 13 .…”

Section: Introductionmentioning

confidence: 97%

Exploring the Link between Serum Phosphate Levels and Low Muscle Strength, Dynapenia, and Sarcopenia

Chen

Kao

Chou

et al. 2018

Sci Rep

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Emerging evidences addressed an association between phosphate and muscle function. Because little attention was focused on this issue, the objective of our study was to explore the relationship of phosphate with muscle strength, dynapenia, and sarcopenia. From the National Health and Nutrition Examination Survey, a total of 7421 participants aged 20 years or older were included in our study with comprehensive examinations included anthropometric parameters, strength of the quadriceps muscle, and appendicular lean masses. Within the normal range of serum phosphate, we used quartile-based analyses to determine the potential relationships of serum phosphate with dynapenia, and sarcopenia through multivariate regression models. After adjusting for the pertinent variables, an inverse association between the serum phosphate quartiles and muscle strength was observed and the linear association was stronger than other anthropometric parameters. Notably, the significant association between phosphate and muscle strength was existed in >65 years old age group, not in 20–65 years old. The higher quartiles of phosphate had higher likelihood for predicting the presence of dynapenia rather than sarcopenia in entire population. Our study highlighted that higher quartiles of phosphate had significant association with lower muscle strength and higher risks for predicting the presence of dynapenia.

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“…Immunohistochemistry was performed with five monoclonal antibodies specific against MHC isoforms: BA–D5 (DMS, Braunschweig, Germany; anti–MHC–I), SC–71 (DMS; anti–MHC–IIa), BF–35 (DMS; anti–MHCs–I plus–IIa and–IIb), S5–8H2 (Biocytex Biotechnology, Marseille, France; anti–MHCs–I plus–IIx and–IIb), and BF–F3 (DMS; anti–MHC–IIb). The specificity of these monoclonal antibodies for MHCs in rat skeletal muscle has previously been reported [ 46 – 48 ]. The immunoperoxidase staining protocol with avidin–biotin complex (ABC) protocol was used as previously described [ 49 ].…”

Section: Methodsmentioning

confidence: 99%

“…The fibers in the selected area were classified according to their MHC content by means of visual examination of immunostainings of the five serial sections stained with the battery of anti–MHC monoclonal antibodies as previously described [ 46 , 47 ]. The reactivity of each individual muscle fiber in these five consecutive sections was judged as positive or negative by comparing the intensity of the reaction of neighbouring fibers.…”

Section: Methodsmentioning

confidence: 99%

Mangiferin protects against adverse skeletal muscle changes and enhances muscle oxidative capacity in obese rats

et al. 2017

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Obesity-related skeletal muscle changes include muscle atrophy, slow-to-fast fiber-type transformation, and impaired mitochondrial oxidative capacity. These changes relate with increased risk of insulin resistance. Mangiferin, the major component of the plant Mangifera indica, is a well-known anti-inflammatory, anti-diabetic, and antihyperlipidemic agent. This study tested the hypothesis that mangiferin treatment counteracts obesity-induced fiber atrophy and slow-to-fast fiber transition, and favors an oxidative phenotype in skeletal muscle of obese rats. Obese Zucker rats were fed gelatin pellets with (15 mg/kg BW/day) or without (placebo group) mangiferin for 8 weeks. Lean Zucker rats received the same gelatin pellets without mangiferin and served as non-obese and non-diabetic controls. Lesser diameter, fiber composition, and histochemical succinic dehydrogenase activity (an oxidative marker) of myosin-based fiber-types were assessed in soleus and tibialis cranialis muscles. A multivariate discriminant analysis encompassing all fiber-type features indicated that obese rats treated with mangiferin displayed skeletal muscle phenotypes significantly different compared with both lean and obese control rats. Mangiferin significantly decreased inflammatory cytokines, preserved skeletal muscle mass, fiber cross-sectional size, and fiber-type composition, and enhanced muscle fiber oxidative capacity. These data demonstrate that mangiferin attenuated adverse skeletal muscle changes in obese rats.

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High-phosphorus diet maximizes and low-dose calcitriol attenuates skeletal muscle changes in long-term uremic rats

Cited by 15 publications

References 52 publications

High-Phosphate Diet Induces Exercise Intolerance and Impairs Fatty Acid Metabolism in Mice

High-Phosphate Diet Induces Exercise Intolerance and Impairs Fatty Acid Metabolism in Mice

Exploring the Link between Serum Phosphate Levels and Low Muscle Strength, Dynapenia, and Sarcopenia

Mangiferin protects against adverse skeletal muscle changes and enhances muscle oxidative capacity in obese rats

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