title: Apolipoprotein a1 increases mitochondrial biogenesis through AMP-activated protein kinase.
abstract: Apolipoprotein a1, which is a major lipoprotein component of high-density lipoprotein (HDL), was reported to decrease plasma glucose in type 2 diabetes. Although recent studies also have shown that apolipoprotein a1 is involved in triglyceride (TG) metabolism, the mechanisms by which apolipoprotein a1 modulates TG levels remain largely unexplored. Here we demonstrated that apolipoprotein a1 increased mitochondrial DNA and mitochondria contents through sustained AMPK activation in myotubes. This resulted in enhanced fatty acid oxidation and attenuation of free fatty acid-induced insulin resistance features in skeletal muscle. The increment of mitochondria was mediated through induction of transcription factors, such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and nuclear transcription factor 1 (NRF-1). The inhibition of AMPK by a pharmacological agent inhibited the induction of mitochondrial biogenesis. Increase of AMPK phosphorylation by apolipoprotein a1 occurs through activation of upstream kinase LKB1. Finally, we confirmed that scavenger receptor Class B, type 1 (SR-B1) is an important receptor for apolipoprotein a1 in stimulating AMPK pathway and mitochondrial biogenesis. Our study suggests that apolipoprotein a1 can alleviate obesity related metabolic disease by inducing AMPK dependent mitochondrial biogenesis.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Republic of Korea.
authors.forename: Parkyong
authors.initials: P
authors.lastname: Song
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Republic of Korea.
authors.forename: Yonghoon
authors.initials: Y
authors.lastname: Kwon
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Republic of Korea.
authors.forename: Kyungmoo
authors.initials: K
authors.lastname: Yea
authors.affiliation: School of Nano-Biotechnology & Chemical Engineering, Ulsan National Institute of Science and Technology, 689-805, Ulsan, Republic of Korea.
authors.forename: Hyo-Youl
authors.initials: HY
authors.lastname: Moon
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Republic of Korea.
authors.forename: Jong Hyuk
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Republic of Korea.
authors.forename: Jaewang
authors.initials: J
authors.lastname: Ghim
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea.
authors.forename: Hyunjung
authors.initials: H
authors.lastname: Hyun
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Republic of Korea.
authors.forename: Dayea
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Republic of Korea.
authors.forename: Ara
authors.initials: A
authors.lastname: Koh
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea; The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Berggren
authors.affiliation: School of Nano-Biotechnology & Chemical Engineering, Ulsan National Institute of Science and Technology, 689-805, Ulsan, Republic of Korea.
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Republic of Korea. Electronic address: sungho@postech.ac.kr.
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008930:Mitochondria, Liver / Q000235:genetics / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; C495634:Nrf1 protein, mouse; D051266:Nuclear Respiratory Factor 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Apolipoprotein a1; Mitochondria; Skeletal muscle