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Diabetologia
Published in: Diabetologia 3/2016

01-03-2016 | Article

BNIP3 is essential for mitochondrial bioenergetics during adipocyte remodelling in mice

Authors: Jin Woo Choi, Anna Jo, Min Kim, Ho Seon Park, Sung Soo Chung, Shinae Kang, Kyong Soo Park

Published in: Diabetologia | Issue 3/2016

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Abstract

Aims/hypothesis

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/interpretation

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.
Appendix
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Metadata
Title
BNIP3 is essential for mitochondrial bioenergetics during adipocyte remodelling in mice
Authors
Jin Woo Choi
Anna Jo
Min Kim
Ho Seon Park
Sung Soo Chung
Shinae Kang
Kyong Soo Park
Publication date
01-03-2016
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 3/2016
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-015-3836-9

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