Ectopic fat accumulation and glucose homeostasis: Ectopic fat accumulation in muscle

Abstract

Adipocytes can serve as energy storage reservoirs against calorie overload. Beyond its capacity, the spillover of stored energy from adipose tissue results in ectopic fat accumulation in tissues, including skeletal muscle. The development of medical technology has enabled the quantification of intramyocellular lipid (IMCL) content. IMCL levels may be regulated by the balance between lipid influx and its mitochondrial oxidation. Therefore, it is plausible that increased IMCL content is strongly associated with insulin resistance, possibly through excessive lipid overload accompanied by obesity and/or mitochondrial dysfunction due to aging and inherited abnormalities such as type 2 diabetes. However, it is known that trained athletes with high insulin sensitivity paradoxically display high levels of IMCL. Therefore, in addition to the quantity of IMCLs, lipid moieties (quality), including diacylglycerol, should be considered to discuss IMCLs and insulin resistance. Recent emerging evidence suggests that intramyocellular enzymes such as diacylglycerol acyltransferase 1 and stearoyl-CoA desaturase-1 can regulate muscle insulin sensitivity regardless of the amount of IMCLs. In this chapter, we focus on IMCLs and insulin resistance considering intramyocellular lipid moieties and insulin signaling.