title: BNIP3 is essential for mitochondrial bioenergetics during adipocyte remodelling in mice.
abstract: OBJECTIVE
  Adipose tissue is a highly versatile system in which mitochondria in adipocytes undergo significant changes during active tissue remodelling. BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) is a mitochondrial protein and a known mitochondrial quality regulator. In this study, we investigated the role of BNIP3 in adipocytes, specifically under conditions of peroxisome proliferator-activated receptor-γ (PPARγ)-induced adipose tissue remodelling.
  
  
  METHODS
  The expression of BNIP3 was evaluated in 3T3-L1 adipocytes in vitro, C57BL/6 mice fed a high-fat diet and db/db mice in vivo. Mitochondrial bioenergetics was investigated in BNIP3-knockdown adipocytes after rosiglitazone treatment. A putative peroxisome proliferator hormone responsive element (PPRE) was characterised by promoter assay and electrophoretic mobility shift assay (EMSA).
  
  
  RESULTS
  The protein BNIP3 was more abundant in brown adipose tissue than white adipose tissue. Furthermore, BNIP3 expression was upregulated by 3T3-L1 pre-adipocyte differentiation, starvation and rosiglitazone treatment. Conversely, BNIP3 expression in adipocytes decreased under various conditions associated with insulin resistance. This downregulation of BNIP3 was restored by rosiglitazone treatment. Knockdown of BNIP3 in adipocytes inhibited rosiglitazone-induced mitochondrial biogenesis and function, partially mediated by the 5' AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor γ, co-activator 1 α (PGC1α) signalling pathway. Rosiglitazone treatment increased the transcription level of Bnip3 in the reporter assay and the presence of the PPRE site in the Bnip3 promoter was demonstrated by EMSA.
  
  
  CONCLUSIONS
  The protein BNIP3 contributes to the improvement of mitochondrial bioenergetics that occurs on exposure to rosiglitazone. It may be a novel therapeutic target for restoring mitochondrial dysfunction under insulin-resistant conditions.
authors.affiliation: Department of Internal Medicine, College of Medicine, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.|Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, College of Medicine, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea.
authors.forename: Anna
authors.initials: A
authors.lastname: Jo
authors.affiliation: Department of Internal Medicine, College of Medicine, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, College of Medicine, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.|Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro (146-92 Dogok-dong), Gangnam-gu, Seoul, 135-710, South Korea.
authors.forename: Ho Seon
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, College of Medicine, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro (146-92 Dogok-dong), Gangnam-gu, Seoul, 135-710, South Korea. shinae95@yuhs.ac.|Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, South Korea. shinae95@yuhs.ac.
authors.forename: Shinae
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, College of Medicine, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea. kspark@snu.ac.kr.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea. kspark@snu.ac.kr.
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D024202:Electrophoretic Mobility Shift Assay; D004734:Energy Metabolism / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D047495:PPAR gamma / Q000494:pharmacology; D016133:Polymerase Chain Reaction
chemical_list: C508686:BNip3 protein, mouse; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D047495:PPAR gamma
keywords: Adipocytes; BNIP3; Bioenergetics; Insulin resistance; Mitochondria; PPRE; Rosiglitazone