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Biochemical and Molecular Actions of Nutrients

Microsomal Triglyceride Transfer Protein Gene Expression and ApoB Secretion Are Inhibited by Bitter Melon in HepG2 Cells^1,2

Pratibha V. Nerurkar^*,3, Laurel Pearson^*,, Jimmy T. Efird^**, Khosrow Adeli, Andre G. Theriault and Vivek R. Nerurkar^,

^* Laboratory of Metabolic Disorders and Alternative Medicine, Department of Molecular Biosciences and Bioengineering, College of Tropical Agriculture and Human Resources; Retrovirology Research Laboratory, ^** Department of Tropical Medicine and Medical Microbiology and Department of Medical Biotechnology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii; and Hospital for Sick Children, University of Toronto, Toronto, Canada

³To whom correspondence should be addressed. E-mail: pratibha{at}hawaii.edu.

Momordica charantia or bitter melon is traditionally used as an antidiabetic agent in Asia, Africa, and South America. Recent studies indicate that bitter melon can also lower plasma lipids and VLDL in diabetic animal models as well as animals fed a high-fat diet, suggesting an effect on lipoprotein metabolism. The aim of this study was to delineate the cellular and molecular mechanisms involved in the lipid-lowering properties of bitter melon and regulation of apolipoprotein B (apoB). Human hepatoma cells, HepG2, treated with bitter melon juice (BMJ) for 24 h reduced apoB secretion with and without the addition of lipids (P < 0.05). However, BMJ did not increase apoB secretion in cells treated with N-acetyl-leucyl-leucyl-norleucinal, indicating a lack of effect on the proteasomal degradation pathway. BMJ reduced the secretion of new triglycerides (P < 0.05) and decreased microsomal triglyceride transfer protein (MTP) mRNA expression, suggesting that lipid bioavailability and lipidation of lipoprotein assembly are likely involved in decreased apoB secretion. Interestingly, BMJ increased the nuclear translocation of the mature form of sterol regulatory element-binding protein-1c (SREBP-1c, P < 0.05), involved in MTP secretion. Our data suggest that BMJ is a potent inhibitor of apoB secretion and TG synthesis and secretion that may be involved in the plasma lipid- and VLDL-lowering effects observed in animal studies.

KEY WORDS: • bitter melon • hyperlipidemia • apolipoprotein B • transcription factors • triglycerides

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