title: The anti-obesity effects of a tuna peptide on 3T3-L1 adipocytes are mediated by the inhibition of the expression of lipogenic and adipogenic genes and by the activation of the Wnt/β-catenin signaling pathway.
abstract: The differentiation of 3T3-L1 cells into adipocytes involves the activation of an organized system of obesity-related genes, of which those encoding CCAAT/enhancer-binding proteins (C/EBPs) and the Wnt-10b protein may play integral roles. In a previous study of ours, we found that a specific peptide found in tuna (sequence D-I-V-D-K-I-E-I; termed TP-D) inhibited 3T3-L1 cell differentiation. In the present study, we observed that the expression of expression of C/EBPs and Wnt-10b was associated with obesity. The initial step of 3T3-L1 cell differentiation involved the upregulation of C/EBP-α expression, which in turn activated various subfactors. An upstream effector of glycogen synthase kinase-3β (GSK-3β) inhibited Wnt-10b expression in 3T3-L1 adipocytes. In a previous study of ours, we sequenced the tuna peptide via sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and quadrupole time-of-flight mass spectrometry (Q-TOF MS/MS) and confirmed the anti-obesity effects thereof in 3T3-L1 adipocytes. In the present study, we demonstrate that TP-D inhibits C/EBP and promotes Wnt-10b mRNA expression, thus activating the Wnt pathway. The inhibition of lipid accumulation was measured using a glucose and triglyceride (TG) assay. Our results confirmed that TP-D altered the expression levels of C/EBP-related genes in a dose-dependent manner and activated the Wnt signaling pathway. In addition, we confirmed that total adiponectin and high-molecular weight (HMW) adiponectin levels were reduced by treatment with TP-D. These data indicate that TP-D inhibits adipocyte differentiation through the inhibition of C/EBP genes and the subsequent activation of the Wnt/β-catenin signaling pathway.
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan 608‑737, Republic of Korea.
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan 608‑737, Republic of Korea.
authors.forename: In-Hye
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan 608‑737, Republic of Korea.
authors.forename: Jeong-Wook
authors.initials: JW
authors.lastname: Choi
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan 608‑737, Republic of Korea.
authors.forename: Min-Kyeong
authors.initials: MK
authors.lastname: Lee
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan 608‑737, Republic of Korea.
authors.forename: Taek-Jeong
authors.initials: TJ
authors.lastname: Nam
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D052242:Adiponectin / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D019440:Anti-Obesity Agents / Q000737:chemistry / Q000494:pharmacology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D050155:Lipogenesis / Q000187:drug effects; D051379:Mice; D009765:Obesity / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism; D014413:Tuna / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D052242:Adiponectin; D019440:Anti-Obesity Agents; D022762:CCAAT-Enhancer-Binding Proteins; D010455:Peptides; D014280:Triglycerides; D051153:Wnt Proteins; C102068:Wnt10b protein, mouse; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D005947:Glucose