1、IntroductionLipid droplets are depots of neutral lipids that exist virtually in any kind of cell.In eukaryotic cells,lipid droplets form the main lipid store.A fundamental component of intracellular lipid homeostasisLD is made of a highly hydrophobic lipid ester core(predominantly TG or cholesteryl
2、esters)and the surface of a phospholipid monolayerRecent studies have revealed that the lipid droplet is not a mere lipid blob,but a major contributor not only to lipid homeostasis but also to diverse cellular functions.formationMorphological characteristicsfunctionBe used for metabolismMembrane syn
3、thesis (phospholipids and cholesterol)Storing cholesterol in the form of cholesteryl esters,as part of the complex homeostatic mechanisms that are involved in regulating the level of intracellular free cholesterolThe structure of membraneThe structure of membrane Molecules in the LD lipids The LDs c
4、ontains TG,diacylglycerol(DG),cholesterol ester(CE),and other esters in various proportions.(different proportion indifferent location)The phospholipid composition of the LD is similar to that of the ER membrane but was not made by random sampling of the ER membrane but,rather,derived from a special
5、 ER domain or formed by an elaborate mechanism.(phosphatidylcholine(PC/磷脂酰胆碱),phosphatidylethanolamine(PE/磷脂酰乙醇胺)phosphatidylinositol(PI/磷脂酰肌醇)FC：the LD of white adipocytes contains a significant amount of free cholesterol and phospholipid PAT-domain proteinsThe PAT-domain(a region of sequence simil
6、arity)family of proteins are some of the best-understood LD components.Contains Contains perilipinperilipin adipophilin/ADRP adipophilin/ADRP（adipose differentiation-related protein）TIP47-related protein domainTIP47-related protein domain（tail-interacting protein of 47kDa）perilipinThe best-character
7、ized PAT-domain protein and the first mammalian protein found as an LD-specific protein.Three isoforms,A,B,and C the adipocyte expresses perilipin A and B the steroidogenic cell has perilipin C The function of perilipinPromotes LDs formationKey components of LDs in adipocytes and steroidogenic cells
8、 Perilipin functions as a shield against cytosolic lipases in the resting condition,but in activated cells,its function is to mediate PKA-activated lipolysis.Perilipin functionally interacts with HSL(hormone-sensitive lipase)and directly involved in the activation of lipolysis.ADRPAdipose Differenti
9、ation Related Proteinexpressed in a wide range of non-adipocytesADRP has been shown to help preserve the cellular TG content,and this may result from its protective function against lipolysis(be similar to perilipin)Has been shown to bind to fatty acids and cholesterol to promote the accumulation of
10、 triglyceride and to stimulate fatty acids uptakeRecent studies indicate that ADRP could bind directly to ARF1,a small GTPase that directly activates PLD1.(Both ARF1 and active PLD1 are localize to LDs,PLD are closely related to the assembly of LDs)In the adipocyte,however,ADRP cannot substitute the
11、 perilipins function as exemplified by the high basal lipolytic rate and low adiposity of the perilipin-null mousethe major function of ADRP is related to partitioning of TG between the LD and the membrane(An increase in TG in the microsome of the ADRP-null mouse liver compared to the normal counter
12、part)TIP47 The physiological role of TIP47 is even more elusive than ADRP.Because knockdown of TIP47 in the ADRP-null fibroblast decreased the number of LDs further.Be also likely to have a protective function against lipolysis Caveolins integral membrane proteins that are usually associated with ce
13、ll-surface pits called caveolae.Caveolin-1 distributes in the caveolae and Golgi membrane under normal culture conditions,but,when cells are loaded with lipids,caveolin-1 is endocytosed by a dynamin-and protein kinase C-dependent pathway and translocates to the LD formationformationfunctionfunctionl
14、ocalized to the surface of LDs and caused an increase in intracellular neutral lipid accumulationthe caveolin-1-dependent transport appears indispensable in maintaining the high FC content of the adipocyte LD the presence of caveolin-1 in the LD core is enigmatic.in certain cell types,caveolae could
15、 function as central regulatory sites for both the synthesis and traffic of triacylglycerols.Recent studies have indicated that triacylglycerols can be synthesized in cell-surface caveolaeMembrane traffickingRab18RabsBe involved in distinct membrane-trafficking steps in the endosomal system or in th
16、e biosynthetic pathway.May facilitate links between LDs and other organelles(such as phagosomes)or coordinate LD motility.Rab18Specific regulated localization to the surface of LDsrecruited to LDs in adipocytes following the stimulation of lipolysis by-adrenergic agonistsThe expression of Rab18 incr
17、eases the wrapping of the ER membrane around LDs.Effectors,facilitate the close apposition of membrane surfacesRab18 localizes to LDs that are lipolytically active and possibly mediates an increased association with the ER to facilitate the transfer of fatty acids or neutral lipids between the LD mo
18、nolayer and the bilayer of the ERLipid droplets and lipolysisLD is still a poorly understood organelleRather than being an inert lipid inclusion,the LD is potentially a central node for the regulation of cellular lipids New insights into the enzymes The connections between LDs and other organelles The role of membrane trafficking and cytoskeletal motility in LD function
