Lipid droplets (LDs) are neutral lipid-containing structures that play an essential role in energy storage and also have additional functions. In addition to being a major structural component of adipocytes (cf. Figs. 164 and 165), they are ubiquitous organelles and their number and size in non-adipocyte cell types can vary greatly. For instance, in liver hepatocytes they are impressively increased following nutritional overload, tissue hypoxia, and poisoning.

By conventional electron microscopy, lipid droplets (LD) are observed as spherical bodies with a rather homogenous content (panel A). Depending on cell type, the core of the lipid droplets consists of varying ratios of triglycerides and cholesterol and of diacylglyceride. Lipid droplet phospholipids are phosphatidylcholine and lysophosphatidylcholine, phophatidylethanolamine and lysophophatidylethanolamine, and phosphatidylinositol. Lipid droplets are limited by a single phospholipid layer, as shown in panel B from cryo-electron microscopic analysis of isolated lipid droplets and as schematically depicted in panel C. Hence, no distinct limiting membrane can be observed by conventional electron microscopy. This is in contrast to other cytoplasmic organelles that are surrounded by a phospholipid bilayer (panels D and E), which can be seen as a double-layered unit membrane. It is generally assumed that the proteins of lipid droplets such as perilipin, adipocyte differentiation-related protein (ADRP), and TIP47 (named PAT proteins) as well as caveolin-1 and a variety of other proteins are embedded in their surface.

For the biogenesis of lipid droplets, various models have been proposed. It is generally agreed that the endoplasmic reticulum is the site of lipid droplet formation, although the initial stage of formation has not convincingly demonstrated by electron microscopy. Panel F illustrates the intimate relationship between the two organelles. The endoplasmic reticulum (ER) forms what is called an ApoB-crescent (arrowheads in panel F) upon immunohistochemical localization of adipocyte differentiation-related protein (ADRP) and apolipoptotein B-100. The ApoB-crescent should not be confused with contact sites between endoplasmic reticulum and lipid droplets (cf. Fig. 97). Panel G depicts schematically two proposed models of lipid droplet biogenesis. They have in common the presence of a tiny lipid ester droplet between the inner and outer phospholipid leaflet of the ER membrane. This lipid droplet leaves the ER either by a budding-fission process, which is currently widely accepted, or by hatching. In either case, the cytoplasmic phospholipid leaflet forms the surface phospholipid layer of the lipid droplet.

Figures A–G from Fujimoto et al. (2008) Histochem Cell Biol 130:263.