Modulation of myocellular fat stores: lipid droplet dynamics in health and disease

Abstract

Storage of fatty acids as triacylglycerol (TAG) occurs in almost all mammalian tissues. Whereas adipose tissue is by far the largest storage site of fatty acids as TAG, subcellular TAG-containing structures--referred to as lipid droplets (LD)--are also present in other tissues. Until recently, LD were considered inert storage sites of energy dense fats. Nowadays, however, LD are increasingly considered dynamic functional organelles involved in many intracellular processes like lipid metabolism, vesicle trafficking, and cell signaling. Next to TAG, LD also contain other neutral lipids such as diacylglycerol. Furthermore, LD are coated by a monolayer of phospholipids decorated with a variety of proteins regulating the delicate balance between LD synthesis, growth, and degradation. Disturbances in LD-coating proteins may result in disequilibrium of TAG synthesis and degradation, giving rise to insulin-desensitizing lipid intermediates, especially in insulin-responsive tissues like skeletal muscle. For a proper and detailed understanding, more information on processes and players involved in LD synthesis and degradation is necessary. This, however, is hampered by the fact that research on LD dynamics in (human) muscle is still in its infancy. A rapidly expanding body of knowledge on LD dynamics originates from studies in other tissues and other species. Here, we aim to review the involvement of LD-coating proteins in LD formation and degradation (LD dynamics) and to extrapolate this knowledge to human skeletal muscle and to explore the role of LD dynamics in myocellular insulin sensitivity.