The lipid droplet (LD) is an organelle enveloped by a monolayer phospholipid membrane with a core of neutral lipids, which is conserved from bacteria to humans. The available evidence suggests that the LD is essential to maintaining lipid homeostasis in almost all organisms. As a consequence, LDs also play an important role in pathological metabolic processes involving the ectopic storage of neutral lipids, including type 2 diabetes mellitus (T2DM), atherosclerosis, steatosis, and obesity. The degree of insulin resistance in T2DM patients is positively correlated with the size of skeletal muscle LDs. Aerobic exercise can reduce the occurrence and development of various metabolic diseases. However, trained athletes accumulate lipids in their skeletal muscle, and LD size in their muscle tissue is positively correlated with insulin sensitivity. This phenomenon is called the athlete’s paradox. This review will summarize previous studies on the relationship between LDs in skeletal muscle and metabolic diseases and will discuss the paradox at the level of LDs.

Lipids stored in skeletal muscle cells are known as intramyocellular lipid (IMCL). Disorders involving IMCL and its causative factor, circulatory free fatty acids (FFAs), induce a toxic state and ultimately result in insulin resistance (IR) in muscle tissue. On the other hand, intramuscular triglyceride (IMTG), the most abundant component of IMCL and an essential energy source for active skeletal muscle, is different from other IMCLs, as it is stored in lipid droplets and plays a pivotal role in skeletal muscle energy homeostasis. This review discusses the association of FFA-induced ectopic lipid accumulation and IR, with specific emphasis on the relationship between IMCL/IMTG metabolism and IR.

Non-alcoholic fatty liver disease (NAFLD) is an epidemic metabolic condition driven by an underlying lipid homeostasis disorder. The lipid droplet (LD), the main organelle involved in neutral lipid storage and hydrolysis, is a potential target for NAFLD therapeutic treatment. In this review, we summarize recent progress elucidating the connections between LD-associated proteins and NAFLD found by genome-wide association studies (GWAS), genomic and proteomic studies. Finally, we discuss a possible mechanism by which the protein 17β-hydroxysteroid dehydrogenase 13 (17β-HSD13) may promote the development of NAFLD.

Kai Zhang, Chang Zhou, Zemin Li, Xuehan Li, Ziyun Zhou, Linjia Cheng, Ahmed Hammad Mirza, Yumeng Shi, Bingbing Chen, Mengwei Zhang, Liujuan Cui, Congyan Zhang,

Lipid droplet (LD) is a monolayer phospholipid membrane-bound organelle found in all eukaryotes and several prokaryotes which plays key roles in cellular lipid homeostasis and human health. The origin and evolution of the organelle remains unknown. Here, we report that through screening over 660 bacteria using biophysical and biochemical methods, plus LD isolation and proteomic tool, LDs were identified in most of these microbes, affiliated with five main bacterial phyla. Moreover, LDs were also identified in E. coli overexpressing lipid synthesis enzymes, indicating that bacteria without detectable LDs possessed the ability of LD biogenesis. The similarity of isolated LDs from representative strains and evolutionary analysis of LD major protein PspA demonstrate that LDs were conserved in bacteria. Furthermore, time-lapse imaging revealed that LDs were inheritable accompanying with bacterial growth and division. Finally, a common ancestor of LD-containing bacteria was predicted to originate 3.19 billion years ago by a phylogenetic analysis. Our findings suggest that LD is a widespread and inheritable organelle from an ancient common ancestor.