Abstract
Muscle atrophy (loss of skeletal muscle mass) causes progressive deterioration of skeletal function. Recently, excessive intake of fats was suggested to induce insulin resistance, followed by muscle atrophy. Green tea extracts (GTEs), which contain polyphenols such as epigallocatechin gallate, have beneficial effects on obesity, hyperglycemia, and insulin resistance, but their effects against muscle atrophy are still unclear. Here, we found that GTEs prevented high-fat (HF) diet–induced muscle weight loss in senescence-accelerated mouse prone-8 (SAMP8), a murine model of senescence. SAMP8 mice were fed a control diet, an HF diet, or HF with 0.5% GTEs (HFGT) diet for 4 months. The HF diet induced muscle weight loss with aging (measured as quadriceps muscle weight), whereas GTEs prevented this loss. In HF diet–fed mice, blood glucose and plasma insulin concentrations increased in comparison with the control group, and these mice had insulin resistance as determined by homeostasis model assessment of insulin resistance (HOMA-IR). In these mice, serum concentrations of leukocyte cell–derived chemotaxin 2 (LECT2), which is known to induce insulin resistance in skeletal muscle, were elevated, and insulin signaling in muscle, as determined by the phosphorylation levels of Akt and p70 S6 kinases, tended to be decreased. In HFGT diet–fed mice, these signs of insulin resistance and elevation of serum LECT2 were not observed. Although our study did not directly show the effect of serum LECT2 on muscle weight, insulin resistance examined using HOMA-IR indicated an intervention effect of serum LECT2 on muscle weight, as revealed by partial correlation analysis. Accordingly, GTEs might have beneficial effects on age-related and HF diet–induced muscle weight loss, which correlates with insulin resistance and is accompanied by a change in serum LECT2.
Highlights
Muscle atrophy—loss of muscle mass—is widely recognized as a risk factor for physical disability and poor quality of life in old age [1,2,3]
We investigated the state of insulin resistance and serum leukocyte cell–derived chemotaxin 2 (LECT2) concentrations in senescence-accelerated mouse prone-8 (SAMP8) mice
Phosphorylation of kinases involved in insulin signaling in skeletal muscle To determine changes in insulin sensitivity caused by diet, we examined the phosphorylation status of Akt and S6 kinase (S6K), which functions downstream of Akt and is important for regulation of protein synthesis [16]
Summary
Muscle atrophy—loss of muscle mass—is widely recognized as a risk factor for physical disability and poor quality of life in old age [1,2,3]. Maintenance of appropriate muscle mass or induction of muscle hypertrophy is achieved by exercise, resistance training, and sufficient nutrient intake [4,5,6,7], but muscle atrophy occurs with aging and senescence [8,9,10]. Hamrick et al developed a useful model for evaluating muscle atrophy in C57BL/6 mice and clearly showed the loss of hindlimb muscle mass from the age of 18 months [11]. Their experimental period was too long for investigating the mechanism of muscle atrophy and testing the therapeutic potential of drugs and food ingredients. In SAMP8 mice, Guo et al revealed that gastrocnemius muscle mass peaked at 7 months and functional and structural decline was observed at 8 months [12]
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