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Evaluating the Activity of Sodium Butyrate to Prevent Osteoporosis in Rats by Promoting Osteal GSK-3β/Nrf2 Signaling and Mitochondrial Function.
- Source :
-
Journal of agricultural and food chemistry [J Agric Food Chem] 2020 Jun 17; Vol. 68 (24), pp. 6588-6603. Date of Electronic Publication: 2020 Jun 08. - Publication Year :
- 2020
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Abstract
- Oxidative stress (OS) and mitochondrial dysfunction are key pathophysiological features of osteoporosis and obesity. Sodium butyrate (NaB), produced by fermentation by the gut microbiota of the large intestine, has been demonstrated to protect against OS by improving specific antioxidant enzymes and to regulate mitochondria redox homeostasis in vivo . Here, in an unblinded study, we identified femur mitochondria as the main target of the beneficial effects of NaB, consisting of reversion of bone loss and body-weight gain in obesity-prone rats. In particular, NaB promoted the activity of mitochondrial antioxidant enzymes and energy metabolism, preserved the bone microstructure and calcium homeostasis, and activated bone metabolism, as shown by increased Nrf2/GSK-3β signaling and the upregulation of PGC-1α and TFAM . In vitro experiments showed that moderate NaB treatment prevented H <subscript>2</subscript> O <subscript>2</subscript> -induced oxidative damage in MC3T3-E1 cells, improved osteoblast mineralization and differentiation, and maintained the balance in bone metabolism by enhancing intracellular antioxidant enzyme activity and ATP production and decreasing the ROS level. In conclusion, NaB promoted the Nrf2/GSK-3β signaling pathway and mitochondrial function and is a potential new therapeutic strategy for obesity and osteoporosis.
- Subjects :
- Adenosine Triphosphate metabolism
Animals
Female
Glycogen Synthase Kinase 3 beta genetics
Humans
Male
Mice
Mice, Inbred C57BL
Mitochondria genetics
Mitochondria metabolism
NF-E2-Related Factor 2 genetics
Osteoporosis genetics
Osteoporosis metabolism
Oxidative Stress drug effects
Rats
Rats, Sprague-Dawley
Butyric Acid administration & dosage
Glycogen Synthase Kinase 3 beta metabolism
Mitochondria drug effects
NF-E2-Related Factor 2 metabolism
Osteoporosis drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1520-5118
- Volume :
- 68
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Journal of agricultural and food chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 32459091
- Full Text :
- https://doi.org/10.1021/acs.jafc.0c01820