MLDP/ perilipin 5 is a widely expressed lipid droplet-associated protein with differential localization in striated myocytes and steatotic hepatocytes

Diseases associated with the accumulation of lipid droplets (LDs) are steadily increasing in western countries. LDs are near-ubiquitous, highly dynamic cell organelles, regulated by LD-associated proteins of the PAT-family (perilipin, adipophilin, TIP47; synonyms perilipin 1–3). Recently, in mouse models and derived cultured cells, MLDP (“myocardial lipid droplet-protein“, synonyms Ox-PAT, perilipin 5), another LD-associated protein of the PAT-family, has been described in highly oxidative tissues such as heart, red muscle and liver during fasting. Yet, little is known about MLDP expression in human tissues and in diseases, in particular hepatocyte steatosis. With rtPCR analysis, highest amounts of MLDP transcripts were detected in liver, skeletal muscle and heart, but minor amounts were also found in some epithelia of the gastrointestinal tract, kidney, prostate gland and steroidogenic tissues. In immunoblot, a protein band of the calculated size of 57 kDa was detected in liver, skeletal muscle and heart. Additional protein bands of 40 and 30 kDa reacted with antibodies produced against MLDP, possibly representing shorter variants. Using a pan tissue microarray comprising about 250 normal human tissues specimens, MLDP was localized in small LDs in heart, striated and smooth muscle, and brown adipose tissue in all specimens analysed, but only in some patients also in liver and some epithelia of the gastrointestinal tract. In fluorescence microscopy, MLDP and other PAT-proteins were differentially expressed in striated myocytes of heart and skeletal muscle and in hepatocytes of liver specimens with different degrees of steatosis pointing to a differential role of MLDP in LD-biogenesis and -storage.In summary, MLDP represents a LD-associated protein predominantly expressed in hepatocytes, myocytes and brown adipocytes. Furthermore, our data point to a more general function of MLDP in LD storage in different tissues than hitherto described.

MLDP - lipid droplet