title: Enzymatic fragments of hyaluronan inhibit adipocyte differentiation in 3T3-L1 pre-adipocytes.
abstract: Hyaluronan has diverse biological activities depending on its molecular size. High molecular weight hyaluronan (2000 kDa) is a major component of extracellular matrix, and has been used in wounding healing, extracellular matrix regeneration, and in the treatment of osteoarthritis. Hyaluronan fragments can stimulate inflammation or induce loss of extracellular matrix. Hyaluronan is expressed during adipocyte differentiation, and down regulation of hyaluronan synthesis can reduce adipogenic differentiation. However, the direct effects of hyaluronan fragments on adipocyte differentiation have not been elucidated. Therefore, we prepared hyaluronan fragments by enzymatic digestion, and examined the inhibitory effects of these hyaluronan fragments on the accumulation of lipid droplets and on adipogenic gene mRNA expression in differentiating 3T3-L1 pre-adipocytes. Medium sized hyaluronan fragments (50 kDa) decreased lipid droplet accumulation in a dose-dependent manner. However, high molecular weight hyaluronan did not inhibit lipid droplet accumulation when used at a concentration of 600 μg/ml. Two or 4 day treatments with medium molecular weight of hyaluronan resulted in similar inhibitory levels of lipid accumulation as did treatment for 8 days. Medium sized hyaluronan inhibited the differentiation of 3T3-L1 pre-adipocytes during the early stages of adipogenesis. When 3T3-L1 cells were treated with 180 μg/ml of medium sized hyaluronan, the mRNAs for the master adipogenic transcription factors PPAR-γ and C/EBP-α were inhibited. Additionally, medium molecular weight hyaluronan suppressed mRNA expression of PPAR-γ target genes, including aP2 and FAS. This study is the first to report that medium molecular weight hyaluronan fragments can inhibit adipocyte differentiation.
authors.affiliation: Department of Physiology, Catholic Kwandong University College of Medicine, Gangneung 210-701, Republic of Korea. Electronic address: bgpark@cku.ac.kr.
authors.forename: Byong-Gon
authors.initials: BG
authors.lastname: Park
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, Bucheon, Gyeonggi-do 420-743, Republic of Korea. Electronic address: idis1985@naver.com.
authors.forename: Chang Won
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Biostream Technologies, Yongin-si, Gyeonggi-do 446-930, Republic of Korea. Electronic address: pjwrnds@empas.com.
authors.forename: Joo Woong
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Yanbian University, Yanji 119, China. Electronic address: cuiyuan1222@163.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Microbiology, Catholic Kwandong University College of Medicine, Gangneung 210-701, Republic of Korea. Electronic address: pyskth@cku.ac.kr.
authors.forename: Yoon-Sun
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Microbiology, Catholic Kwandong University College of Medicine, Gangneung 210-701, Republic of Korea. Electronic address: shinws@cku.ac.kr.
authors.forename: Woon-Seob
authors.initials: WS
authors.lastname: Shin
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008970:Molecular Weight
chemical_list: D006820:Hyaluronic Acid
keywords: Adipocyte differentiation; Adipogenic inhibitor; Hyaluronan; Hyaluronan fragments; PPAR-gamma