ABSTRACT
The conversion of skeletal muscle fiber from fast twitch to slow-twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid (TCA) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber-type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain IIb expression. Further, by using pharmacological or genetic loss-of-function models generated by phospholipase Cß antagonists, SUNCR1 global knockout, or SUNCR1 gastrocnemius-specific knockdown, we found that the effects of succinate on skeletal muscle fiber-type remodeling are mediated by SUNCR1 and its downstream calcium/NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUNCR1 signaling pathway. These findings suggest the potential beneficial use of succinate-based compounds in both athletic and sedentary populations.
Subject(s)
Muscle Fibers, Skeletal/drug effects , Muscle Fibers, Skeletal/metabolism , Muscle, Skeletal/metabolism , Succinic Acid/pharmacology , Animals , Citric Acid Cycle/drug effects , Male , Mice , Mice, Inbred C57BL , Muscle Contraction/drug effects , Muscle Fatigue/drug effects , Muscle, Skeletal/drug effects , Myosin Heavy Chains/metabolism , Oxygen Consumption/drug effects , Signal Transduction/drug effectsABSTRACT
OBJECTIVE: To observe the effects of comprehensive therapy on serum secreted protein acidic and rich in cysteine (SPARC) levels in ankylosing spondylitis (AS) patients accompanied with osteoporosis (OP), and to explore the possible mechanisms for SPARC in AS patients accompanied with osteoporosis. METHODS: Totally 48 AS patients accompanied with OP (Group A) were treated with massage, intravenous infusion of Cervus and Cucumis Polypeptide Injection, and Bushen Quhan Zhiwang Decoction (BQZD) for 3 months. At the same time, 45 normal healthy subjects were recruited as the normal control group (Group B). Serum SPARC levels were measured by ELISA in Group A before and after comprehensive therapy and in those of Group B. The levels of bone mineral density of femoral neck (FN BMD), bone mineral density of 2 -4 lumbar spine (L2-4 BMD), bone specific alkaline phosphatase (BSAP), tumor necrosis factor alpha (TNF-alpha), and transforming growth factor beta-1 (TGF-beta1) were detected. Meanwhile, Bath AS disease activity index (BASDAI) and Bath AS functional index (BASFI) were detected in Group A before and after treatment. The correlations between the aforesaid indices and serum SPARC levels were analyzed. RESULTS: Serum SPARC levels were significantly lower in those of Group A than in those of Group B (175. 30 +/- 72.04 micro/L vs 190. 52 +/- 86. 13 microg/ L, P <0. 01). Serum SPARC levels in those of Group A were negatively correlated with TNF-alpha (r = -0.261, P <0.01), positively with L2-4 BMD, TGF-beta1, and BSAP (r =0.437,0.256, 0.385, P <0.05, P <0.01). L2-4BMD and BSAP were independently predictors of serum SPARC in patients of Group A. After comprehensive therapy, the levels of TNF-alpha, BASDAI, and BASFI obviously decreased, TGF-beta1, BSAP, L2-4 BMD, and FN BMD obviously increased (P <0. 05, P <0. 01). The serum SPARC levels also significantly increased (188.32 +/- 87.50 microg/L, P <0. 05). CONCLUSION: Comprehensive therapy could effectively improve the bone metabolism, clinical symptoms and the activity function of joints, and elevate serum SPARC levels.
Subject(s)
Osteonectin/blood , Osteoporosis/blood , Spondylitis, Ankylosing/blood , Adolescent , Adult , Bone Density , Case-Control Studies , Combined Modality Therapy , Cysteine/blood , Drugs, Chinese Herbal/therapeutic use , Female , Humans , Male , Middle Aged , Osteoporosis/complications , Osteoporosis/therapy , Spondylitis, Ankylosing/complications , Spondylitis, Ankylosing/therapy , Young AdultABSTRACT
OBJECTIVE: To investigate the relationship of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor beta1 (TGF-beta1) with the occurrence of ankylosing spondylitis (AS), and the effects of Bushen Tongdu Decoction (BTD) on serum TNF-alpha and TGF-beta1, levels in patients. METHODS: Seventy five AS patients were assigned to two groups, 30 in the group I treated with Azulfidine and35 in the group II treated with BTD. ELISA was adopted to detect the levels of TNF-alpha and TGF-beta1, in patients before and after 24-week treatment. Meantime, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured as well. Besides, the levels of TNF-alpha and TGF-beta1 in 30 healthy persons were also detected for normal control. RESULTS: Before treatment, as compared with normal control, the TNF-alpha increased and TGF-beta1 decreased (P < 0.01) in the two treatment groups; the serum level of TNF-alpha was positively correlated with ESR and CRP (r = 0.296, r = 0.249; P < 0.05), but the serum level of TGF-beta1 showed no correlation with them (r = -0.222, r = -0.203; P > 0.05). After treatment, TGF-beta1 increased, while TNF-alpha, CRP and ESR decreased in group II (P < 0.01). CONCLUSION: BTD can regulate TNF-alpha and TGF-beta1 levels to suppress the immune inflammatory reaction so as to treat AS.
