Autor: |
Daniel J Fazakerley, Rima Chaudhuri, Pengyi Yang, Ghassan J Maghzal, Kristen C Thomas, James R Krycer, Sean J Humphrey, Benjamin L Parker, Kelsey H Fisher-Wellman, Christopher C Meoli, Nolan J Hoffman, Ciana Diskin, James G Burchfield, Mark J Cowley, Warren Kaplan, Zora Modrusan, Ganesh Kolumam, Jean YH Yang, Daniel L Chen, Dorit Samocha-Bonet, Jerry R Greenfield, Kyle L Hoehn, Roland Stocker, David E James |
Jazyk: |
angličtina |
Rok vydání: |
2018 |
Předmět: |
|
Zdroj: |
eLife, Vol 7 (2018) |
Druh dokumentu: |
article |
ISSN: |
2050-084X |
DOI: |
10.7554/eLife.32111 |
Popis: |
Insulin resistance in muscle, adipocytes and liver is a gateway to a number of metabolic diseases. Here, we show a selective deficiency in mitochondrial coenzyme Q (CoQ) in insulin-resistant adipose and muscle tissue. This defect was observed in a range of in vitro insulin resistance models and adipose tissue from insulin-resistant humans and was concomitant with lower expression of mevalonate/CoQ biosynthesis pathway proteins in most models. Pharmacologic or genetic manipulations that decreased mitochondrial CoQ triggered mitochondrial oxidants and insulin resistance while CoQ supplementation in either insulin-resistant cell models or mice restored normal insulin sensitivity. Specifically, lowering of mitochondrial CoQ caused insulin resistance in adipocytes as a result of increased superoxide/hydrogen peroxide production via complex II. These data suggest that mitochondrial CoQ is a proximal driver of mitochondrial oxidants and insulin resistance, and that mechanisms that restore mitochondrial CoQ may be effective therapeutic targets for treating insulin resistance. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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