Antioxidant treatment induces reductive stress associated with mitochondrial dysfunction in adipocytes
Artikel i vetenskaplig tidskrift, 2018

β-Adrenergic stimulation of adipose tissue increases mitochondrial density and activity (browning) that are associated with improved whole-body metabolism. Whereas chronically elevated levels of reactive oxygen species (ROS) in adipose tissue contribute to insulin resistance, transient ROS elevation stimulates physiological processes such as adipogenesis. Here, using a combination of biochemical and cell and molecular biology–based approaches, we studied whether ROS or antioxidant treatment affects β3-adrenergic receptor (β3-AR) stimulation–induced adipose tissue browning. We found that β3-AR stimulation increases ROS levels in cultured adipocytes, but, unexpectedly, pretreatment with different antioxidants (N-acetylcysteine, vitamin E, or glutathione ethyl ester) did not prevent this ROS increase. Using fluorescent probes, we discovered that the antioxidant treatments instead enhanced β3-AR stimulation–induced mitochondrial ROS production. This pro-oxidant effect of antioxidants was, even in absence of β3-AR stimulation, associated with decreased oxygen consumption and increased lactate production in adipocytes. We observed similar antioxidant effects in wildtype mice:N-acetylcysteine blunted β3-AR stimulation–induced browning of white adipose tissue and reduced mitochondrial activity in brown adipose tissue even in the absence of β3-AR stimulation. Furthermore, N-acetylcysteine increased the levels of peroxiredoxin 3 and superoxide dismutase 2 in adipose tissue, indicating increased mitochondrial oxidative stress. We interpret this negative impact of antioxidants on oxygen consumption in vitro and adipose tissue browning in vivo as essential adaptations that prevent a further increase in mitochondrial ROS production. In summary, these results suggest that chronic antioxidant supplementation can produce a paradoxical increase in oxidative stress associated with mitochondrial dysfunction in adipocytes.

mitochondria

reactive oxygen species (ROS)

adipocyte

antioxidant

metabolism

adrenergic receptor

adipose tissue

Browning

Glutathione

vitamin E

N-acetylcysteine

oxidative stress

Författare

Eduard Peris

Göteborgs universitet

Peter Micallef

Göteborgs universitet

Alexandra Paul

Chalmers, Biologi och bioteknik, Kemisk biologi

Vilborg Palsdottir

Göteborgs universitet

Marco Bauzá-Thorbrügge

Göteborgs universitet

Charlotta S Olofsson

Göteborgs universitet

Ingrid Wernstedt Asterholm

Göteborgs universitet

Journal of Biological Chemistry

0021-9258 (ISSN) 1083-351X (eISSN)

Ämneskategorier

Cell- och molekylärbiologi

Fysiologi

Medicinsk bioteknik

DOI

10.1074/jbc.RA118.004253

Mer information

Skapat

2018-12-20