Effects of skeletal muscle lipotoxicity on muscle protein synthesis: implications for athletic and ageing populations

References: Andderson SR, et al. (2008). Metabolism, 57, 347–354. Guillet C, et al. (2009). J. Clin. Endocrinol. Metab., 94, 3044–3050 Katsanos CS, et al. (2011). Obesity, 19, 469–475 Masgrau A, et al. (2012). J. Physiol., 590, 5199-5210 Tardif N, et al. (2011). Clin. Nutr., 30, 799-806 Tardif N, et al. (2014). Aging Cell, 13, 1001-1011Ectopic lipid accumulation in skeletal muscle is linked to reduced insulin sensitivity in various groups of subjects. The increased lipid content within muscle in older people is independently associated with insulin resistance. Physical exercise improves muscle lipid infiltration and insulin resistance in postmenopausal women. Beside the consequence of muscle fat accumulation on insulin sensitivity, some evidences clearly show that high fat feeding in young mice influences the ability of muscle to hypertrophy in response to anabolic stimuli (Anderson, 2008). In addition, muscle fat accumulation in older people is associated with poorer strength and poor physical performance and subsequent disability. A negative relationship has been highlighted between body fat mass and muscle protein synthesis in young and elderly people (Guillet, 2009; Katsanos, 2011). These observation suggest that an increase in adipose or ectopic fat mass may affect protein kinetics within skeletal muscle. Recent data have clearly shown that intra-muscular lipid deposition during aging affects protein synthesis via impairment in the regulation of a specific factor of intracellular signaling pathway of insulin: eIF2-alpha (Tardif, 2014). This effect has also been demonstrated in adult rats in which lipid accumulation in muscles during prolonged obesity is deleterious for amino acid incorporation in skeletal muscle proteins (Masgrau, 2012). In vitro and in vivo data have shown that the deleterious effect of intramuscular fat accumulation on muscle protein synthesis might be due to a specific reactive lipid species. Indeed the accumulation of ceramides within muscle is linked with the reduction of muscle protein synthesis and the hyperphosphorylation of eIF2-alpha (Tardif, 2014). The effect of muscle lipotoxicity on muscle protein synthesis could also be due to an indirect effect through the modulation of insulin sensitivity and inflammation by the nature of lipids ingested. For instance, in old rats fed a high-fat oleate-enriched diet, insulin sensitivity and inflammation are improved and concomitantly skeletal muscle protein synthesis is enhanced (Tardif, 2011). Recent data provide strong arguments for the involvement of muscle lipotoxicity in reduction of muscle protein synthesis during ageing. This process may contribute to the loss of muscle mass and function observed in elderly people, defined as “sarcopenia