Blunted angiogenesis and hypertrophy are associated with increased fatigue resistance and unchanged aerobic capacity in old overloaded mouse muscle.

We hypothesize that the attenuated hypertrophic response in old mouse muscle is (1) partly due to a reduced capillarization and angiogenesis, which is (2) accompanied by a reduced oxidative capacity and fatigue resistance in old control and overloaded muscles, that (3) can be rescued by the antioxidant resveratrol. To investigate this, the hypertrophic response, capillarization, oxidative capacity, and fatigue resistance of m. plantaris were compared in 9- and 25-month-old non-treated and 25-month-old resveratrol-treated mice. Overload increased the local capillary-to-fiber ratio less in old (15 %) than in adult (59 %) muscle (P < 0.05). Although muscles of old mice had a higher succinate dehydrogenase (SDH) activity (P < 0.05) and a slower fiber type profile (P < 0.05), the isometric fatigue resistance was similar in 9- and 25-month-old mice. In both age groups, the fatigue resistance was increased to the same extent after overload (P < 0.01), without a significant change in SDH activity, but an increased capillary density (P < 0.05). Attenuated angiogenesis during overload may contribute to the attenuated hypertrophic response in old age. Neither was rescued by resveratrol supplementation. Changes in fatigue resistance with overload and aging were dissociated from changes in SDH activity, but paralleled those in capillarization. This suggests that capillarization plays a more important role in fatigue resistance than oxidative capacity

Blunted hypertrophic response in old mouse muscle is associated with a lower satellite cell density and is not alleviated by resveratrol

Background Sarcopenia contributes to the decreased quality of life in the older person. While resistance exercise is an effective measure to increase muscle mass and strength, the hypertrophic response may be blunted in old age. Objectives To determine 1) whether hypertrophy in the m. plantaris of old mice was blunted compared to adult and 2) whether this was related to a reduced satellite cell (SC) density and 3) how resveratrol affects hypertrophy in old mice. Methods In adult (7.5 months, n = 11), old (23.5 months, n = 10) and old-resveratrol-treated (n = 10) male C57BL/6J mice, hypertrophy of the left m. plantaris was induced by denervation of its synergists. The contralateral leg served as control. Results After six weeks, overload-induced myofiber hypertrophy and IIB–IIA shift in myofiber type composition were less pronounced in old than adult mice (P = 0.03), irrespective of resveratrol treatment. Muscles from old mice had a lower SC density than adult muscles (P = 0.002). Overload-induced SC proliferation (P < 0.05) resulted in an increased SC density in old, but not adult muscles (P = 0.02), while a decrease occurred after resveratrol supplementation (P = 0.044). Id2 and myogenin protein expression levels were higher in old than adult muscles (P < 0.05). Caspase-3 was expressed more in hypertrophied than control muscles and was reduced with resveratrol (P < 0.05). Conclusion The blunted hypertrophic response in old mice was associated with a lower SC density, but there was no evidence for a lower capacity for proliferation. Resveratrol did not rescue the hypertrophic response and even reduced, rather than increased, the number of SCs in hypertrophied muscles

Repeated-sprint performance and plasma responses following beetroot juice supplementation do not differ between recreational, competitive and elite sprint athletes

Purpose: There is an ongoing debate whether highly trained athletes are less responsive to the ergogenic properties of nitrate. We assessed the effects of nitrate supplementation on plasma nitrate and nitrite concentrations and repeated-sprint performance in recreational, competitive and elite sprint athletes. Methods: In a randomized double-blinded cross-over design, recreational cyclists (n=20), national talent speed-skaters (n=22) and Olympic-level track cyclists (n=10) underwent two 6-day supplementation periods; 140mL/d nitrate-rich (BR; approximate to 800mg/d) and nitrate-depleted (PLA; approximate to 0.5mg/d) beetroot juice. Blood samples were collected and three 30-s Wingate tests were performed. Results: Plasma nitrate and nitrite concentrations were higher following BR vs PLA (P&lt;.001), with no differences between sport levels (all P&gt;.10). Peak power over the three Wingates was not different between BR and PLA (1338 +/- 30 vs 1333 +/- 30 W; P=.62), and there was no interaction between treatment (BR-PLA) and Wingate number (1-2-3; P=.48). Likewise, mean power did not differ between BR and PLA (P=.86). In contrast, time to peak power improved by approximate to 2.8% following BR vs PLA (P=.007). This improvement in BR vs PLA was not different between Wingate 1, 2 and 3.Moreover, the effects of BR vs PLA did not differ between sport levels for any Wingate parameter (all P&gt;.30). Conclusion: The plasma and repeated-sprint performance responses to beetroot juice supplementation do not differ between recreational, competitive and elite sprint athletes. Beetroot juice supplementation reduces time to reach peak power, which may improve the capacity to accelerate during high-intensity and sprint tasks in recreational as well as elite athletes

Repeated-sprint performance and plasma responses following beetroot juice supplementation do not differ between recreational, competitive and elite sprint athletes

Purpose: There is an ongoing debate whether highly trained athletes are less responsive to the ergogenic properties of nitrate. We assessed the effects of nitrate supplementation on plasma nitrate and nitrite concentrations and repeated-sprint performance in recreational, competitive and elite sprint athletes. Methods: In a randomized double-blinded cross-over design, recreational cyclists (n = 20), national talent speed-skaters (n = 22) and Olympic-level track cyclists (n = 10) underwent two 6-day supplementation periods; 140 mL/d nitrate-rich (BR; ∼800 mg/d) and nitrate-depleted (PLA; ∼0.5 mg/d) beetroot juice. Blood samples were collected and three 30-s Wingate tests were performed. Results: Plasma nitrate and nitrite concentrations were higher following BR vs PLA (P .10). Peak power over the three Wingates was not different between BR and PLA (1338 ± 30 vs 1333 ± 30 W; P = .62), and there was no interaction between treatment (BR-PLA) and Wingate number (1-2-3; P = .48). Likewise, mean power did not differ between BR and PLA (P = .86). In contrast, time to peak power improved by ∼2.8% following BR vs PLA (P = .007). This improvement in BR vs PLA was not different between Wingate 1, 2 and 3. Moreover, the effects of BR vs PLA did not differ between sport levels for any Wingate parameter (all P > .30). Conclusion: The plasma and repeated-sprint performance responses to beetroot juice supplementation do not differ between recreational, competitive and elite sprint athletes. Beetroot juice supplementation reduces time to reach peak power, which may improve the capacity to accelerate during high-intensity and sprint tasks in recreational as well as elite athletes

Interleukin-37 suppresses the osteogenic responses of human aortic valve interstitial cells in vitro and alleviates valve lesions in mice

Item does not contain fulltextCalcific aortic valve disease is a chronic inflammatory process, and aortic valve interstitial cells (AVICs) from diseased aortic valves express greater levels of osteogenic factors in response to proinflammatory stimulation. Here, we report that lower cellular levels of IL-37 in AVICs of diseased human aortic valves likely account for augmented expression of bone morphogenetic protein-2 (BMP-2) and alkaline phosphatase (ALP) following stimulation of Toll-like receptor (TLR) 2 or 4. Treatment of diseased AVICs with recombinant human IL-37 suppresses the levels of BMP-2 and ALP as well as calcium deposit formation. In mice, aortic valve thickening is observed when exposed to a TLR4 agonist or a high fat diet for a prolonged period; however, mice expressing human IL-37 exhibit significantly lower BMP-2 levels and less aortic valve thickening when subjected to the same regimens. A high fat diet in mice results in oxidized low-density lipoprotein (oxLDL) deposition in aortic valve leaflets. Moreover, the osteogenic responses in human AVICs induced by oxLDL are suppressed by recombinant IL-37. Mechanistically, reduced osteogenic responses to oxLDL in human AVICs are associated with the ability of IL-37 to inhibit NF-kappaB and ERK1/2. These findings suggest that augmented expression of osteogenic factors in AVICs of diseased aortic valves from humans is at least partly due to a relative IL-37 deficiency. Because recombinant IL-37 suppresses the osteogenic responses in human AVICs and alleviates aortic valve lesions in mice exposed to high fat diet or a proinflammatory stimulus, IL-37 has therapeutic potential for progressive calcific aortic valve disease

Interleukin-37 treatment of mice with metabolic syndrome improves insulin sensitivity and reduces pro-inflammatory cytokine production in adipose tissue

Obesity and the metabolic syndrome are characterized by chronic, low-grade inflammation mainly originating from expanding adipose tissue and resulting in inhibition of insulin signaling and disruption of glycemic control.Transgenic mice expressing human interleukin 37 (IL-37),an anti-inflammatory cytokine of the IL-1 family,are protected against metabolic syndrome when fed a high-fat diet (HFD) containing 45% fat. Here, we examined whether treatment with recombinant IL-37 ameliorates established insulin resistance and obesity-induced inflammation. WT mice were fed a HFD for 22 weeks and then treated daily with IL-37 (1 ug/mouse) during the last 2 weeks. Compared with vehicle only-treated mice, IL-37-treated mice exhibited reduced insulin in the plasma and had significant improvements in glucose tolerance and in insulin content of the islets.The IL-37 treatment also increased the levels of circulating IL-1 receptor antagonist. Cultured adipose tissues revealed that IL-37 treatment significantly decreases spontaneous secretions of IL-1β, tumor necrosis factor α (TNFα), and CXC motif chemokine ligand 1 (CXCL-1). We also fed mice a 60% fat diet with concomitant daily IL-37 for 2 weeks and observed decreased secretion of IL-1β, TNFα, and IL-6 and reduced intracellular levels of IL-1β in the liver and adipose tissue, along with improved plasma glucose clearance. Compared with vehicle treatment, these IL-37-treated mice had no apparent weight gain. In human adipose tissue cultures, the presence of 50 pM IL-37 reduced spontaneous release of TNF and 50% of lipopolysaccharide-induced TNFα. These findings indicate that IL-37's anti-inflammatory effects can ameliorate established metabolic disturbances during obesity.</p