Antioxidant treatment induces reductive stress associated with mitochondrial dysfunction in adipocytes
Artikel i vetenskaplig tidskrift, 2019

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.

vitamin E

reactive oxygen species (ROS)




adipose tissue



adrenergic receptor

oxidative stress




Eduard Peris

Göteborgs universitet

Peter Micallef

Göteborgs universitet

Alexandra Paul

Chalmers, Biologi och bioteknik, Kemisk biologi

Vilborg Palsdottir

Göteborgs universitet

Annika Enejder

Chalmers, Biologi och bioteknik, Kemisk biologi

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)

Vol. 294 7 2340-2352


Cell- och molekylärbiologi


Medicinsk bioteknik





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