Vitamin D₃ intake modulates diaphragm but not peripheral muscle force in young mice

Abstract

Recent data support an important role for vitamin D in respiratory health. We tested the hypothesis that dietary vitamin D3 (VD3) intake modulates diaphragm (DIA) strength. Four-week-old female A/J mice (n = 10/group) were randomized to receive diets containing 100 IU VD3/kg (low), 1,000 IU VD3/kg (reference), or 10,000 IU VD3/kg (pharmacologic). After 6 wk of dietary intervention, plasma 25-hydroxyvitamin D3 (25D3) levels, DIA and extensor digitorum longus (EDL) in vitro contractile properties, and fiber cross-sectional area (CSA) were measured. Myosin heavy chain (MHC) composition and Akt/Foxo3A growth signaling were studied in the DIA and tibialis anterior. Mice fed the low, reference, and pharmacologic diets had average 25D3 levels of 7, 21, and 59 ng/ml, respectively. Maximal DIA force, twitch force, and fiber CSA were reduced 26%, 28%, and 10% (P < 0.01), respectively, in mice receiving the low-VD3 diet compared with the reference and pharmacologic diets. EDL force parameters were unaltered by diet. Effects of VD3 intake on DIA force were not observed in mice that began dietary intervention at 12 wk of age. VD3 intake did not alter the MHC composition of the DIA, indicating that decreases in force and CSA in young mice were not due to a switch in fiber type. Paradoxically, low VD3 intake was associated with activation of anabolic signaling in muscle (hyperphosphorylation of Akt and Foxo3A and decreased expression of autophagy marker LC3). These studies identify a potential role of dietary VD3 in regulating DIA development and insulin sensitivity.

Vitamin D Supplementation and Impact on Skeletal Muscle Function in Cell and Animal Models and an Aging Population: What Do We Know So Far?

“…Interestingly, VitD3 associated with a Mediterranean diet resulted in synergetic effect of muscle fibre hypertrophy when compared with regular diet with VitD3 only for 10 weeks in male rats [ 40 ] ( Table 2 ). A similar female mouse model was studied to identify the best dose-effect of VitD3 for skeletal muscle function and the authors found that a low dose (100 IU/day) for 6 weeks significantly decreased maximal DIA force, twitch force and CSA fibres when compared with the other groups that had a higher dose of VitD3 (1000 and 10,000 of VitD3/kg food) [ 39 ] ( Table 2 ). Overall, VitD3 treatments had positive effects on the development of muscle fibres cells, skeletal muscle force and hypertrophy in mice.…”

Mechanisms of vitamin D action in skeletal muscle

“…The majority of animal studies have focused on the physiological effects of vitamin D on muscle mass and strength (53)(54)(55) and most have not investigated the precise pathways regulating the reported outcomes. At the cellular level, some studies have investigated the effects of vitamin D in murine cell lines, such as C 2 C 12 (Table 2), and demonstrated that treatment with vitamin D inhibits cell proliferation (23,(55)(56)(57)(58)(59) and stimulates cell differentiation (25,58,60,61) .…”

“…Subsequent studies with VDR knockout (VDR-KO) mice, and with also mice subjected to a vitamin D-deficient diet (Table 1), have reported significant muscular atrophy, weakened strength, decreased muscle fibre size, lower bone mineral density and dysregulation of myogenic regulatory factors when compared with control groups, i.e. normal mice and mice receiving a vitamin D-sufficient diet (46,(53)(54)(55) . Moreover, Oku et al (53) have demonstrated the negative impact of vitamin D deficiency on the levels of mRNA expression of MyoD in skeletal muscle tissue, which corroborates the importance of vitamin D for the process of myogenesis, muscle maintenance and hypertrophy.…”

Cholecalciferol in ethanol-preferring rats muscle fibers increases the number and area of type II fibers

“…There are differences in the mitochondria quantity related to oxidative and glycolytic muscular fibers and their metabolic responses should be taken into consideration (Schiaffino and Reggiani, 2011). In addition the supplementation of vitamin D is able to promote an improvement in parameters of mitochondrial function (Sinha et al, 2013) and according to Ray et al (2016) its effects are muscle-specific.…”