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Antioxidant treatme...
Antioxidant treatment induces reductive stress associated with mitochondrial dysfunction in adipocytes
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- Peris, Eduard (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,University of Gothenburg
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- Micallef, Peter, 1988 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,University of Gothenburg
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- Paul, Alexandra, 1988 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Palsdottir, Vilborg, 1979 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,University of Gothenburg
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- Enejder, Annika, 1969 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Bauzá-Thorbrügge, Marco (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,University of Gothenburg
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- Olofsson, Charlotta S, 1971 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,University of Gothenburg
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- Wernstedt Asterholm, Ingrid, 1978 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,University of Gothenburg
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(creator_code:org_t)
- 2019
- 2019
- English.
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 294:7, s. 2340-2352
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Abstract
Subject headings
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- beta-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 beta 3-adrenergic receptor (beta 3-AR) stimulation-induced adipose tissue browning. We found that beta 3-AR stimulation increases ROS levels in cultured adipocytes, but, unexpectedly, pretreatment with different antioxidants (N-acetylcysteine, vitamin E, or GSH ethyl ester) did not prevent this ROS increase. Using fluorescent probes, we discovered that the antioxidant treatments instead enhanced beta 3-AR stimulation-induced mitochondrial ROS production. This pro-oxidant effect of antioxidants was, even in the absence of beta 3-AR stimulation, associated with decreased oxygen consumption and increased lactate production in adipocytes. We observed similar antioxidant effects in WT mice: N-acetylcysteine blunted beta 3-AR stimulation-induced browning of white adipose tissue and reduced mitochondrial activity in brown adipose tissue even in the absence of beta 3-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.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
- TEKNIK OCH TEKNOLOGIER -- Industriell bioteknik -- Medicinsk bioteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Industrial Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- reactive oxygen species (ROS)
- adipose tissue
- adrenergic receptor
- antioxidant
- vitamin E
- mitochondria
- oxidative stress
- adipocyte
- metabolism
- browning
- glutathione
- N-acetylcysteine
- increased oxidative stress
- glutathione
- ros
- differentiation
- expression
- nrf2
- cell
- Biochemistry & Molecular Biology
- adipocyte
Publication and Content Type
- ref (subject category)
- art (subject category)
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