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NRF2 is essential f...
NRF2 is essential for adaptative browning of white adipocytes.
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- Bauzá-Thorbrügge, Marco (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,University of Gothenburg,Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden
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- Peris Franquet, Eduard (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,University of Gothenburg,Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden
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- Zamani, Shabnam (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,University of Gothenburg,Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden
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- Micallef, Peter, 1988 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,University of Gothenburg,Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden
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- Paul, Alexandra, 1988 (författare)
- The University of Texas at Austin, USA,Chalmers tekniska högskola,Chalmers University of Technology,Department of Biology and Biological Engineering, Division of Chemical Biology, Chalmers University of Technology, Gothenburg, Sweden ; The Department of Biomedical Engineering, University of Texas at Austin, TX, United States
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- Bartesaghi, Stefano (författare)
- AstraZeneca AB,Bioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
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- Benrick, Anna, 1979 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,University of Gothenburg,Högskolan i Skövde,University of Skövde,Institutionen för hälsovetenskaper,Forskningsmiljön hälsa, hållbarhet och digitalisering,Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden,Translationell medicin TRIM, Translational Medicine TRIM
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- Wernstedt Asterholm, Ingrid, 1978 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,University of Gothenburg,Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden
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(creator_code:org_t)
- Elsevier, 2023
- 2023
- Engelska.
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Ingår i: Redox biology. - : Elsevier. - 2213-2317. ; 68
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https://doi.org/10.1...
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https://gup.ub.gu.se...
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Abstract
Ämnesord
Stäng
- White adipose tissue browning, defined by accelerated mitochondrial metabolism and biogenesis, is considered a promising mean to treat or prevent obesity-associated metabolic disturbances. We hypothesize that redox stress acutely leads to increased production of reactive oxygen species (ROS), which activate electrophile sensor nuclear factor erythroid 2-Related Factor 2 (NRF2) that over time results in an adaptive adipose tissue browning process. To test this, we have exploited adipocyte-specific NRF2 knockout mice and cultured adipocytes and analyzed time- and dose-dependent effect of NAC and lactate treatment on antioxidant expression and browning-like processes. We found that short-term antioxidant treatment with N-acetylcysteine (NAC) induced reductive stress as evident from increased intracellular NADH levels, increased ROS-production, reduced oxygen consumption rate (OCR), and increased NRF2 levels in white adipocytes. In contrast, and in line with our hypothesis, longer-term NAC treatment led to a NRF2-dependent browning response. Lactate treatment elicited similar effects as NAC, and mechanistically, these NRF2-dependent adipocyte browning responses in vitro were mediated by increased heme oxygenase-1 (HMOX1) activity. Moreover, this NRF2-HMOX1 axis was also important for β3-adrenergic receptor activation-induced adipose tissue browning in vivo. In conclusion, our findings show that administration of exogenous antioxidants can affect biological function not solely through ROS neutralization, but also through reductive stress. We also demonstrate that NRF2 is essential for white adipose tissue browning processes.
Ämnesord
- 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)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- Mice
- Animals
- Adipocytes
- White
- metabolism
- NF-E2-Related Factor 2
- genetics
- metabolism
- Antioxidants
- pharmacology
- metabolism
- Reactive Oxygen Species
- metabolism
- Adipose Tissue
- White
- metabolism
- Acetylcysteine
- pharmacology
- Lactates
- metabolism
- Redox stress
- Translationell medicin TRIM
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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