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Microsome-associated lumenal lipid droplets in the regulation of lipoprotein secretion

Yao, Zemina; Zhou, Hub; Figeys, Daniela; Wang, Yuweia; Sundaram, Meenakshia

Current Opinion in Lipidology: April 2013 - Volume 24 - Issue 2 - p 160–170
doi: 10.1097/MOL.0b013e32835aebe7
GENETICS AND MOLECULAR BIOLOGY: Edited by Robert Hegele

Purpose of review: Liver is the major organ in mammals that possesses the capacity to release triglyceride within VLDL. VLDL assembly requires apolipoprotein (apo) B-100 with the assistance of microsomal triglyceride transfer protein (MTP), which facilitates the mobilization of triglyceride into the microsomal lumen. Recent experimental evidence has suggested that the lumenal triglyceride associated with endoplasmic reticulum (ER)/Golgi may represent an entity serving as precursors for large VLDL1.

Recent findings: Under lipid-rich conditions, discrete triglyceride-rich lipidic bodies, termed lumenal lipid droplets, are accumulated in association with ER/Golgi microsomes. Formation of the microsome-associated lumenal lipid droplets (MALD) is dependent on the activity of MTP, and the resulting apoB-free lipidic body is associated with a variety of proteins including apolipoproteins that are components of VLDL. Formation and utilization of MALD during the assembly and secretion of VLDL1 have a profound influence on hepatic cell physiology, such as ER stress responses.

Summary: This review summarizes current understanding of hepatic triglyceride homeostasis in general, and highlights the functional significance of triglyceride compartmentalization between cytosol and microsomes in particular. Understanding of MALD metabolism may shed new light on the prevention and treatment of liver diseases associated with abnormally elevated intracellular triglycerides.

aDepartment of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada

bChinese Academy of Sciences, Shanghai Institute of Materia Medica, Shanghai, China

Correspondence to Zemin Yao, Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada. Tel: +1 613 5625800 x8202; e-mail: zyao@uottawa.ca

© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins