OM2, a Novel Oligomannuronate-Chromium(III) Complex, Promotes Mitochondrial Biogenesis and Lipid Metabolism in 3T3-L1 Adipocytes via the AMPK-PGC1α Pathway

Jiejie Hao; Cui Hao; Lijuan Zhang; Xin Liu; Xiaolin Zhou; Yunlou Dun; Haihua Li; Guangsheng Li; Xiaoliang Zhao; Yuanyuan An; Jiankang Liu; Guangli Yu

doi:10.1371/journal.pone.0131930

OM2, a Novel Oligomannuronate-Chromium(III) Complex, Promotes Mitochondrial Biogenesis and Lipid Metabolism in 3T3-L1 Adipocytes via the AMPK-PGC1α Pathway

PLoS One. 2015 Jul 15;10(7):e0131930. doi: 10.1371/journal.pone.0131930. eCollection 2015.

Authors

Affiliations

¹ 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.
² 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.

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.

Methodology/principal findings: 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/significance: 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3-L1 Cells
AMP-Activated Protein Kinases / antagonists & inhibitors
AMP-Activated Protein Kinases / genetics
AMP-Activated Protein Kinases / metabolism
Animals
Chromium / chemistry*
Coordination Complexes / chemistry
Coordination Complexes / pharmacology*
DNA, Mitochondrial / metabolism
Lipase / genetics
Lipase / metabolism
Lipid Metabolism / drug effects*
Lipid Peroxidation / drug effects
Mannans / chemistry
Mannans / pharmacology*
Mice
Mitochondria / drug effects
Mitochondria / metabolism*
Mitochondrial Proteins / genetics
Mitochondrial Proteins / metabolism
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Plasmids / genetics
Plasmids / metabolism
Promoter Regions, Genetic
RNA Interference
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Small Interfering / metabolism
Real-Time Polymerase Chain Reaction
Signal Transduction / drug effects*
Transcription Factors / antagonists & inhibitors
Transcription Factors / genetics
Transcription Factors / metabolism

Substances

Coordination Complexes
DNA, Mitochondrial
Mannans
Mitochondrial Proteins
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Ppargc1a protein, mouse
RNA, Messenger
RNA, Small Interfering
Transcription Factors
oligomannurarate sulfate
oligomannuronate-chromium (III) complex OM2
Chromium
AMP-Activated Protein Kinases
Lipase
PNPLA2 protein, mouse

Grants and funding

This study was supported by NSFC-Shandong Joint Fund for Marine Science Research Centers (U1406402), the NSFC (81402982), the Special Fund for Marine Scientific Research in the Public Interest (201005024), the National Key Technology R&D Program of the Ministry of Science and Technology (2013BAB01B02), and the 973 Program (2015CB553602). No potential conflicts of interest relevant to this article were reptorted. The funders had no role in the design and conduct of the study, in the collection, analysis, and interpretation of data, or in the preparation, review, or approval of the manuscript.