Abstract
BackgroundMuscle wasting is frequently a result of cancers, AIDS, chronic diseases and aging, which often links to muscle inflammation. Although grape seed extract (GSE) has been widely used as a human dietary supplement for health promotion and disease prevention primarily due to its anti-oxidative and anti-inflammative effects, it is unknown whether GSE affects muscle wasting. The objective is to test the effects of GSE supplementation on inflammation and muscle wasting in interleukin (IL)-10 knockout mice, a recently developed model for human frailty.MethodsMale IL-10 knockout (IL10KO) C57BL/6 mice at 6 weeks of age were assigned to either 0% or 0.1% GSE (in drinking water) groups (n = 10) for 12 weeks, when skeletal muscle was sampled for analyses. Wild-type C57BL/6 male mice were used as controls.ResultsTibialis anterior muscle weight and fiber size of IL10KO mice were much lower than wild-type mice. IL10KO enhanced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling and inflammasome formation when compared to wild-type mice. Phosphorylation of anabolic signaling was inhibited, whereas muscle specific ubiquitin ligase, AMP-activated protein kinase (AMPK) and apoptotic signaling were up-regulated in IL10KO mice. GSE supplementation effectively rectified these adverse changes in IL10KO muscle, which provide an explanation for the enhanced muscle mass, reduced protein degradation and apoptosis in GSE supplemented mice compared to IL10KO mice without supplementation.ConclusionGSE supplementation effectively prevents muscle wasting in IL10KO mice, showing that GSE can be used as an auxiliary treatment for muscle loss associated with chronic inflammation and frailty.
Highlights
Muscle wasting is frequently a result of cancers, AIDS, chronic diseases and aging, which often links to muscle inflammation
Interleukin 10 knockout (IL10KO) reduced weight gain when compared to WT mice, and grape seed extract (GSE) supplementation improved weight gain of IL10KO (Figure 1A)
The muscle fibers in GSE treated mice and control mice were round and larger than those of IL10KO mice without supplementation (Figure 1D). These data clearly show that GSE, despite a low dose, was effective in preventing muscle loss in IL10KO mice
Summary
Muscle wasting is frequently a result of cancers, AIDS, chronic diseases and aging, which often links to muscle inflammation. The objective is to test the effects of GSE supplementation on inflammation and muscle wasting in interleukin (IL)-10 knockout mice, a recently developed model for human frailty. IL10KO mice show accelerated muscle loss and weakness [20], and chronic inflammation, ideal for assessing inflammation associated muscle wasting and frailty [19,21]. Using this mouse model, the objective of this study is to test the effectiveness of GSE in preventing muscle loss in IL10KO mice and further explore underlying mechanisms
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