title: Molecular Mechanism of Betaine on Hepatic Lipid Metabolism: Inhibition of Forkhead Box O1 (FoxO1) Binding to Peroxisome Proliferator-Activated Receptor Gamma (PPARγ).
abstract: Betaine is a major water-soluble component of Lycium chinensis. Although there are reports about the protective effects of betaine on hepatic steatosis, the underlying mechanisms are unclear. We used db/db mice and HepG2 cells to examine the mechanism underlying betaine-mediated protection against hepatic steatosis. Here, we showed increased hepatic lipid accumulation in db/db mice, which is associated with increased activation of lipogenic transcription factors including forkhead box O1 (FoxO1) and peroxisome proliferator-activated receptor gamma (PPARγ), whereas betaine administration by oral gavage reversed these characteristics. We investigated whether betaine ameliorates hepatic steatosis by inhibiting FoxO1/PPARγ signaling in HepG2 cells. Although adenovirus-mediated FoxO1 overexpression notably increased mRNA expression levels of PPARγ and its target genes including FAS and ACC, betaine treatment reversed them. Furthermore, betaine inhibited FoxO1 binding to the PPARγ promoter and PPARγ transcriptional activity in HepG2 cells, which was previously shown to induce hepatic steatosis. We concluded that betaine ameliorates hepatic steatosis, at least in part, by inhibiting the FoxO1 binding to PPARγ and their downstream lipogenic signaling cascade.
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University , Busan 609-735, Republic of Korea.
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University , Busan 609-735, Republic of Korea.
authors.forename: Bonggi
authors.initials: B
authors.lastname: Lee
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University , Busan 609-735, Republic of Korea.
authors.forename: Min Jo
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University , Busan 609-735, Republic of Korea.
authors.forename: Min Hi
authors.initials: MH
authors.lastname: Park
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University , Busan 609-735, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: An
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University , Busan 609-735, Republic of Korea.
authors.forename: Eun Kyeong
authors.initials: EK
authors.lastname: Lee
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University , Busan 609-735, Republic of Korea.
authors.forename: Ki Wung
authors.initials: KW
authors.lastname: Chung
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University , Busan 609-735, Republic of Korea.
authors.forename: June Whoun
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Physiology, The University of Texas Health Science Center at San Antonio , San Antonio, Texas 78229, United States.
authors.forename: Byung Pal
authors.initials: BP
authors.lastname: Yu
authors.affiliation: Department of Food and Life Science, Pukyong National University , Busan 608-737, Republic of Korea.
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University , Busan 609-735, Republic of Korea.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000818:Animals; D001622:Betaine / Q000494:pharmacology*; D005234:Fatty Liver / Q000188:drug therapy*; D000071161:Forkhead Box Protein O1 / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism; D050155:Lipogenesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000378:metabolism*
chemical_list: D000071161:Forkhead Box Protein O1; C467200:Foxo1 protein, mouse; D047495:PPAR gamma; D001622:Betaine
keywords: FoxO1; PPARγ; betaine; lipogenesis; steatosis