Methionine sulfoxide reductase B1 deficiency does not increase high-fat diet-induced insulin resistance in mice.
Jung-Yoon Heo, Hye-Na Cha, Ki Young Kim, Eujin Lee, Suk-Jeong Kim, Yong-Woon Kim, Jong-Yeon Kim, In-Kyu Lee, Vadim N Gladyshev, Hwa-Young Kim, So-Young Park
Author Information
Jung-Yoon Heo: a Department of Physiology , College of Medicine, Yeungnam University , Daegu , Republic of Korea.
Hye-Na Cha: a Department of Physiology , College of Medicine, Yeungnam University , Daegu , Republic of Korea.
Ki Young Kim: b Department of Biochemistry and Molecular Biology, College of Medicine , Yeungnam University , Daegu , Republic of Korea.
Eujin Lee: b Department of Biochemistry and Molecular Biology, College of Medicine , Yeungnam University , Daegu , Republic of Korea.
Suk-Jeong Kim: a Department of Physiology , College of Medicine, Yeungnam University , Daegu , Republic of Korea.
Yong-Woon Kim: a Department of Physiology , College of Medicine, Yeungnam University , Daegu , Republic of Korea.
Jong-Yeon Kim: a Department of Physiology , College of Medicine, Yeungnam University , Daegu , Republic of Korea.
In-Kyu Lee: c Department of Internal Medicine, School of Medicine , Kyungpook National University , Daegu , Republic of Korea.
Vadim N Gladyshev: d Division of Genetics, Department of Medicine Brigham and Women's Hospital , Harvard Medical School , Boston , MA , USA.
Hwa-Young Kim: b Department of Biochemistry and Molecular Biology, College of Medicine , Yeungnam University , Daegu , Republic of Korea.
So-Young Park: a Department of Physiology , College of Medicine, Yeungnam University , Daegu , Republic of Korea.
Methionine-S-sulfoxide reductase (MsrA) protects against high-fat diet-induced insulin resistance due to its antioxidant effects. To determine whether its counterpart, methionine-R-sulfoxide reductase (MsrB) has similar effects, we compared MsrB1 knockout and wild-type mice using a hyperinsulinemic-euglycemic clamp technique. High-fat feeding for eight weeks increased body weights, fat masses, and plasma levels of glucose, insulin, and triglycerides to similar extents in wild-type and MsrB1 knockout mice. Intraperitoneal glucose tolerance test showed no difference in blood glucose levels between the two genotypes after eight weeks on the high-fat diet. The hyperglycemic-euglycemic clamp study showed that glucose infusion rates and whole body glucose uptakes were decreased to similar extents by the high-fat diet in both wild-type and MsrB1 knockout mice. Hepatic glucose production and glucose uptake of skeletal muscle were unaffected by MsrB1 deficiency. The high-fat diet-induced oxidative stress in skeletal muscle and liver was not aggravated in MsrB1-deficient mice. Interestingly, whereas MsrB1 deficiency reduced JNK protein levels to a great extent in skeletal muscle and liver, it markedly elevated phosphorylation of JNK, suggesting the involvement of MsrB1 in JNK protein activation. However, this JNK phosphorylation based on a p-JNK/JNK level did not positively correlate with insulin resistance in MsrB1-deficient mice. Taken together, our results show that, in contrast to MsrA deficiency, MsrB1 deficiency does not increase high-fat diet-induced insulin resistance in mice.
