Intramyocellular lipid content (IMCL)

Intramyocellular lipid (IMCL) content refers to the quantity of lipids, primarily triacylglycerols (IMTG), stored within the sarcoplasm of skeletal muscle fibers [5, 7, 17]. Under normal physiological conditions, these lipids serve as a vital energy substrate during physical exertion; however, their excessive accumulation—known as ectopic lipid deposition—is a significant feature of obesity and type 2 diabetes [4, 12, 15]. High muscle lipid content is strongly associated with insulin resistance, primarily through the accumulation of lipotoxic metabolites such as ceramides and diacylglycerols that disrupt downstream insulin signaling pathways [4, 5, 19]. In the context of aging and sarcopenia, elevated IMCL levels correlate with a decline in muscle quality, reduced physical performance, and anabolic resistance [1, 3, 13]. While not a molecular target in the traditional sense of a receptor or enzyme, IMCL is considered a critical phenotypic target in drug development, with research focusing on agents that enhance mitochondrial fatty acid oxidation or systemic energy homeostasis to reduce its pathological accumulation [1, 3, 8, 18]. Non-invasive monitoring of IMCL via proton magnetic resonance spectroscopy (1H-MRS) provides a valuable biomarker for evaluating metabolic health and the efficacy of therapeutic interventions targeting lipid metabolism [6, 13].

Other names

Muscle lipid contentIntramuscular triglyceridesIMTGEctopic skeletal muscle lipidsMyocellular lipid depositionIntramyocellular lipids

Pharmacological modulation of muscle lipid content is typically achieved through the activation of AMP-activated protein kinase (AMPK) to stimulate fatty acid oxidation, the activation of Peroxisome proliferator-activated receptors (PPARs) to upregulate lipid-handling genes, and the use of incretin mimetics to improve systemic energy balance and reduce ectopic lipid deposition [1, 3, 9, 15, 18].