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Cholesteryl ester transfer protein deficiency in adipocytes disrupts triglyceride metabolism in multiple ways
Author(s) -
Greene Diane Jackel,
Morton Richard E
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1020.1
Subject(s) - endoplasmic reticulum , cholesterylester transfer protein , chemistry , lipid droplet , triglyceride , adipocyte , lipid metabolism , intracellular , cholesteryl ester , adipose triglyceride lipase , acyltransferase , biochemistry , diglyceride , endocrinology , medicine , enzyme , biology , adipose tissue , cholesterol , lipoprotein
Previous studies implicate cholesteryl ester transfer protein (CETP) in the intracellular transport of triglyceride (TG) from the endoplasmic reticulum (ER) to lipid storage droplets (LD). Here, we further characterize TG metabolism in modified SW872 adipocytes expressing only 25% of normal CETP. Measured by oleate incorporation, TG synthesis in CETP deficient cells was 75% of control but in vivo transport of this newly synthesized TG from the ER to LD was only 40% of control, correlating with the reduced ability of these cells to accumulate TG in LD. Despite reduced transfer, the TG content of cellular membranes was not increased. During TG biosynthesis, CETP deficient cells accumulated a high level of diglyceride (DG), a pathway intermediate. Although TG synthesis was lower, TG + DG synthesis in CETP deficient cells was 140% of control. Consistent with this, mRNA and protein levels of glycerol 3‐phosphate acyltransferase were elevated. DG acyltransferase 1 and 2 mRNA levels were unchanged but adipocyte TG lipase mRNA was increased 2.2 fold. The mismatch between rates of TG synthesis and storage in CETP deficient adipocytes may result from the failure to translocate TG from the ER to LD, subsequently impairing DGAT activity and/or inducing TG hydrolysis in the ER, causing a rise in DG. Intracellular CETP appears to be necessary for efficient synthesis of storage lipids and their targeting to lipid droplets. NIH HL060934