title: OM2, a Novel Oligomannuronate-Chromium(III) Complex, Promotes Mitochondrial Biogenesis and Lipid Metabolism in 3T3-L1 Adipocytes via the AMPK-PGC1α Pathway.
abstract: BACKGROUND
  In our previous studies, we prepared novel oligomannuronate-chromium(III) complexes (OM2, OM4) from marine alginate, and found that these compounds sensitize insulin action better than oligomannuronate(OM), chromium, and metformin in C2C12 skeletal muscle cells. In the present study, we studied their effects on mitochondrial biogenesis, lipid metabolism, and the underlying molecular mechanisms in differentiated 3T3-L1 adipocytes.
  
  
  RESULTS
  We firstly used the pGL3-PGC1α and pGL3-ATGL promoter plasmids to compare their effects on PGC1α and ATGL transcription activities. Then mitochondrial biogenesis was quantified by transmission electron microscopy and MitoTracker staining. Mitochondrial oxygen consumption and fatty acid oxidation were measured by an oxygen biosensor system and ³H-labelled water scintillation. The mitochondrial DNA and mRNA involved in mitochondrial biogenesis and lipid oxidation were evaluated by real-time PCR. AMPK together with other protein expression levels were measured by western blotting. The inhibitor compound C and siRNA of PGC1α were used to inhibit the OM2-induced AMPK-PGC1α signaling pathway. And we found that OM2 stimulated AMPK-PGC1α pathway in the 3T3-L1 adipocytes, which were correlated with induced mitochondrial biogenesis, improved mitochondrial function, and reduced lipid accumulation by enhanced fatty acid β-oxidation and augmented ATGL protein expression.
  
  
  CONCLUSIONS
  Our data indicated that the marine oligosaccharide-derived OM2 might represent a novel class of molecules that could be useful for type 2 diabetes prevention and treatment by up-regulating AMPK-PGC1α signaling pathway.
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, 266003, China.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Hao
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, 266003, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Hao
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, 266003, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, 266003, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, 266003, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, 266003, China.
authors.forename: Yunlou
authors.initials: Y
authors.lastname: Dun
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, 266003, China.
authors.forename: Haihua
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, 266003, China.
authors.forename: Guangsheng
authors.initials: G
authors.lastname: Li
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, 266003, China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, 266003, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: An
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, 266003, China.
authors.forename: Guangli
authors.initials: G
authors.lastname: Yu
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002857:Chromium / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D004272:DNA, Mitochondrial / Q000378:metabolism; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008351:Mannans / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000217:Acyltransferases
chemical_list: D055372:AMP-Activated Protein Kinases; D002857:Chromium; D056831:Coordination Complexes; D004272:DNA, Mitochondrial; D008049:Lipase; D008351:Mannans; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; C485290:Ppargc1a protein, mouse; C524388:oligomannurarate sulfate; C000607120:oligomannuronate-chromium (III) complex OM2; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases