Effects of alfacalcidol on circulating cytokines and growth factors in rat skeletal muscle

Abstract

Supra-physiological levels of vitamin D induce skeletal muscle atrophy, which may be particularly detrimental in already sarcopaenic elderly. Neither the cause nor whether the atrophy is fibre type specific are known. To obtain supraphysiological levels of circulating vitamin D (1,25(OH) 2 D 3 ) 27.5-month-old female Fischer 344 9 Brown Norway F1 rats were orally treated for 6 weeks with vehicle or the vitamin D analogue alfacalcidol. Alfacalcidol treatment induced a 22% decrease in body mass and 17% muscle atrophy. Fibre atrophy was restricted to type IIb fibres in the low-oxidative part of the gastrocnemius medialis only (-22%; P \ 0.05). There was a concomitant 1.6-fold increase in mRNA expression of the ubiquitin ligase MuRF-1 (P \ 0.001), whereas those of insulin-like growth factor 1 and myostatin were not affected. Circulating IL-6 was unaltered, but leptin and adiponectin were decreased (-39%) and increased (64%), respectively. The treated rats also exhibited a reduced food intake. In conclusion, supraphysiological levels of circulating 1,25(OH) 2 D 3 cause preferential atrophy of type IIb fibres, which is associated with an increased expression of MuRF-1 without evidence of systemic inflammation. The atrophy and loss of body mass in the presence of supra-physiological levels of vitamin D are primarily due to a reduced food intake.

Chronic vitamin D insufficiency impairs physical performance in C57BL/6J mice

“…Belenchia et al [ 33 ] also observed loss of lean mass in mice due to dietary vitamin D deficiency (serum 25‑OH vitamin D < 10 ng/ml) of approximately 40 weeks in female mice initiated at 8 weeks of age. We suspect our study was underpowered to identify such histological differences; however, the possibility that vitamin D insufficient mice exhibit smaller fast twitch fiber CSA is supported by our finding that vitamin D insufficient mice also exhibit greater expression of atrogin-1, for which this and other atrophy associated proteins have previously been linked to vitamin D signaling [ 27 , 34 , 35 ]. Thus these data support the notion that long-term vitamin D insufficiency may contribute to the progression of sarcopenia.…”

Attenuated Increase in Maximal Force of Rat Medial Gastrocnemius Muscle after Concurrent Peak Power and Endurance Training

“…Tubes were heated at 25°C for 5 min, followed by 42°C for 20 min. Finally, to stop the reaction, the tubes were heated at 85°C for 5 min and stored at −80°C until used in the quantitative PCR reaction (method described previously) [19]. Expression levels of mRNA were assessed for insulin-like growth factor 1Ea (IGF-1Ea), myostatin, α -skeletal actin, muscle ring finger 1 (MuRF-1) and muscle atrophy F-box (MAFbx; also known as artogin 1) (see Table 1 for primer sequences).…”

Effects of Concurrent Training on Oxidative Capacity in Rat Gastrocnemius Muscle

“…Tubes were heated at 25-C for 5 min, followed by 42-C for 20 min. Finally, to stop the reaction, the tubes were heated at 85-C for 5 min and stored at j80-C until used in the quantitative polymerase chain reaction (PCR) (method described previously) (27). Expression levels of mRNA were assessed for SDH, PGC-1>, receptor-interacting protein 140 (RIP140), and BCL2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) (see Table 1 for primer sequences).…”