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Resistance to Obesity in SOD1 Deficient Mice with a High-Fat/High-Sucrose Diet
Atsushi Sato1, Yasunaga Shiraishi2, Toyokazu Kimura1
1Department of Internal Medicine, Division of Cardiovascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan.
Abstract:
Metabolic syndrome (Mets) is an important condition because it may cause stroke and heart disease in the future. Reactive oxygen species (ROSs) influence the pathogenesis of Mets; however, the types of ROSs and their localization remain largely unknown. In this study, we investigated the effects of SOD1, which localize to the cytoplasm and mitochondrial intermembrane space and metabolize superoxide anion, on Mets using SOD1 deficient mice (SOD1-/-). SOD1-/- fed on a high-fat/high-sucrose diet (HFHSD) for 24 weeks showed reduced body weight gain and adipose tissue size compared to wild-type mice (WT). Insulin secretion was dramatically decreased in SOD1-/- fed on HFHSD even though blood glucose levels were similar to WT. Ambulatory oxygen consumption was accelerated in SOD1-/- with HFHSD; however, ATP levels of skeletal muscle were somewhat reduced compared to WT. Reflecting the reduced ATP, the expression of phosphorylated AMPK (Thr 172) was more robust in SOD1-/-. SOD1 is involved in the ATP production mechanism in mitochondria and may contribute to visceral fat accumulation by causing insulin secretion and insulin resistance.
Insights
Mice lacking SOD1 showed reduced weight gain and fat accumulation on a high-fat diet. This suggests SOD1 plays a role in metabolic syndrome development by influencing insulin secretion and energy production.
Area of Science:
- Biochemistry
- Metabolic Research
- Mitochondrial Biology
Background:
- Metabolic syndrome (Mets) increases future risks of stroke and heart disease.
- Reactive oxygen species (ROSs) are implicated in Mets pathogenesis, but specific ROS types and locations are unclear.
- Superoxide dismutase 1 (SOD1) metabolizes superoxide anions and is found in cytoplasm and mitochondrial intermembrane space.
Purpose of the Study:
- To investigate the role of SOD1 in metabolic syndrome.
- To examine the impact of SOD1 deficiency on metabolic parameters in mice fed a high-fat/high-sucrose diet (HFHSD).
Main Methods:
- Utilized SOD1-deficient mice (SOD1-/-) and wild-type (WT) littermates.
- Administered a high-fat/high-sucrose diet (HFHSD) for 24 weeks.
- Assessed body weight, adipose tissue, insulin secretion, blood glucose, oxygen consumption, skeletal muscle ATP levels, and AMPK phosphorylation.
Main Results:
- SOD1-/- mice exhibited reduced body weight gain and adipose tissue size compared to WT mice on HFHSD.
- Insulin secretion was significantly decreased in SOD1-/- mice, despite similar blood glucose levels.
- Accelerated oxygen consumption and reduced skeletal muscle ATP levels were observed in SOD1-/- mice, with increased phosphorylated AMPK (Thr 172).
Conclusions:
- SOD1 is involved in mitochondrial ATP production.
- SOD1 deficiency impacts visceral fat accumulation, insulin secretion, and insulin resistance.
- These findings highlight SOD1's potential role in the complex mechanisms underlying metabolic syndrome.
