Methionine sulfoxide reductase B1 deficiency does not increase high-fat diet-induced insulin resistance in mice

Free Radic Res. 2017 Jan;51(1):24-37. doi: 10.1080/10715762.2016.1261133. Epub 2016 Dec 9.


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.

Keywords: Methionine sulfoxide; antioxidant; high-fat diet; hyperinsulinemic-euglycemic clamp; insulin resistance.

MeSH terms

  • Animals
  • Blood Glucose
  • Diet, High-Fat / adverse effects*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Insulin Resistance*
  • Liver / enzymology
  • MAP Kinase Kinase 4 / metabolism
  • Male
  • Methionine Sulfoxide Reductases / genetics*
  • Methionine Sulfoxide Reductases / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Skeletal / enzymology
  • Oxidative Stress
  • Phosphorylation
  • Protein Processing, Post-Translational


  • Blood Glucose
  • Methionine Sulfoxide Reductases
  • MsrB1 protein, mouse
  • Extracellular Signal-Regulated MAP Kinases
  • MAP Kinase Kinase 4