title: Methionine sulfoxide reductase B1 deficiency does not increase high-fat diet-induced insulin resistance in mice.
abstract: 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.
authors.affiliation: a Department of Physiology , College of Medicine, Yeungnam University , Daegu , Republic of Korea.
authors.forename: Jung-Yoon
authors.initials: JY
authors.lastname: Heo
authors.affiliation: a Department of Physiology , College of Medicine, Yeungnam University , Daegu , Republic of Korea.
authors.forename: Hye-Na
authors.initials: HN
authors.lastname: Cha
authors.affiliation: b Department of Biochemistry and Molecular Biology, College of Medicine , Yeungnam University , Daegu , Republic of Korea.
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Kim
authors.affiliation: b Department of Biochemistry and Molecular Biology, College of Medicine , Yeungnam University , Daegu , Republic of Korea.
authors.forename: Eujin
authors.initials: E
authors.lastname: Lee
authors.affiliation: a Department of Physiology , College of Medicine, Yeungnam University , Daegu , Republic of Korea.
authors.forename: Suk-Jeong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: a Department of Physiology , College of Medicine, Yeungnam University , Daegu , Republic of Korea.
authors.forename: Yong-Woon
authors.initials: YW
authors.lastname: Kim
authors.affiliation: a Department of Physiology , College of Medicine, Yeungnam University , Daegu , Republic of Korea.
authors.forename: Jong-Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: c Department of Internal Medicine, School of Medicine , Kyungpook National University , Daegu , Republic of Korea.
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Lee
authors.affiliation: d Division of Genetics, Department of Medicine Brigham and Women's Hospital , Harvard Medical School , Boston , MA , USA.
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
authors.affiliation: b Department of Biochemistry and Molecular Biology, College of Medicine , Yeungnam University , Daegu , Republic of Korea.
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: a Department of Physiology , College of Medicine, Yeungnam University , Daegu , Republic of Korea.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Park
mesh_terms: D000818:Animals; D001786:Blood Glucose; D059305:Diet, High-Fat / Q000009:adverse effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D051150:Methionine Sulfoxide Reductases / Q000235:genetics* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000201:enzymology; D018384:Oxidative Stress; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational
chemical_list: D001786:Blood Glucose; D051150:Methionine Sulfoxide Reductases; C000614737:MsrB1 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4
keywords: Methionine sulfoxide; antioxidant; high-fat diet; hyperinsulinemic-euglycemic clamp; insulin resistance