Related Experiment Video
Updated: Jul 15, 2026
Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease with Fibrosis
Published on: July 18, 2025
D-galactose toxicity in mice is associated with mitochondrial dysfunction: protecting effects of mitochondrial
Jiangang Long1, Xuemin Wang, Hongxiang Gao
1Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Abstract:
D-galactose (D-gal) -induced aging models in Drosophila, houseflies, mice and rats have been widely used; however, the underlying mechanisms are poorly understood. To investigate the involvement of mitochondrial dysfunction of D-gal, mitochondrial function was examined in the brain and liver of C57BL/6J mice, subjected to a treatment of D-gal with or without a concomitant treatment with a mitochondrial nutrient, R-alpha-lipoic acid (LA). D-Gal treatment induced a significant decrease in succinate-linked respiratory control ratio (RCR) and ADP/O ratio in the liver and brain, and also a significant increase in the maximum velocity (Vmax) and substrate binding affinity (Km) of complex II in the liver. LA treatment to D-gal-injected animals restored mitochondrial RCR in both brain and liver, ADP/O and Km of complex II in the liver. These results suggest LA is effective in delaying D-gal toxicity by ameliorating mitochondrial dysfunction.
Insights
D-galactose (D-gal) causes aging by impairing mitochondrial function. R-alpha-lipoic acid (LA) treatment effectively reversed this mitochondrial dysfunction, suggesting LA can delay D-galactose toxicity.
Area of Science:
- Biogerontology
- Mitochondrial Biology
- Neuroscience
Background:
- D-galactose (D-gal) is a widely used inducer of aging models.
- The precise mechanisms underlying D-gal-induced aging, particularly concerning mitochondrial dysfunction, remain unclear.
Purpose of the Study:
- To investigate the role of mitochondrial dysfunction in D-galactose-induced aging.
- To evaluate the protective effects of R-alpha-lipoic acid (LA) against D-galactose toxicity at the mitochondrial level.
Main Methods:
- Mice (C57BL/6J) were treated with D-galactose, with or without R-alpha-lipoic acid (LA).
- Mitochondrial function, including respiratory control ratio (RCR), ADP/O ratio, and Complex II kinetics (Vmax, Km), was assessed in brain and liver tissues.
Main Results:
- D-galactose treatment significantly decreased RCR and ADP/O ratios in brain and liver.
- D-galactose increased Vmax and Km of Complex II in the liver.
- LA treatment restored mitochondrial RCR in brain and liver, and normalized ADP/O and Km of Complex II in the liver.
Conclusions:
- D-galactose induces mitochondrial dysfunction, contributing to aging.
- R-alpha-lipoic acid (LA) effectively ameliorates D-galactose-induced mitochondrial impairment.
- LA shows potential as a therapeutic agent to delay D-galactose toxicity and aging.
