title: Microsomal triglyceride transfer protein gene expression and ApoB secretion are inhibited by bitter melon in HepG2 cells.
abstract: 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.
authors.affiliation: Laboratory of Metabolic Disorders and Alternative Medicine, Department of Molecular Biosciences and Bioengineering, College of Tropical Agriculture and Human Resources, University of Hawaii, Honolulu, HI, USA. pratibha@hawaii.edu
authors.forename: Pratibha V
authors.initials: PV
authors.lastname: Nerurkar
authors.forename: Laurel
authors.initials: L
authors.lastname: Pearson
authors.forename: Jimmy T
authors.initials: JT
authors.lastname: Efird
authors.forename: Khosrow
authors.initials: K
authors.lastname: Adeli
authors.forename: Andre G
authors.initials: AG
authors.lastname: Theriault
authors.forename: Vivek R
authors.initials: VR
authors.lastname: Nerurkar
mesh_terms: D001055:Apolipoproteins B / Q000378:metabolism*; D001483:Base Sequence; D001628:Beverages; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D019662:Cucurbitaceae; D003600:Cytosol / Q000378:metabolism; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008861:Microsomes / Q000502:physiology*; D019301:Oleic Acid / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000235:genetics
chemical_list: D001055:Apolipoproteins B; D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; C106092:microsomal triglyceride transfer protein; D019301:Oleic Acid