Leptin Administration Downregulates the Increased Expression Levels of Genes Related to Oxidative Stress and Inflammation in the Skeletal Muscle ofob/obMice

Abstract

Obese leptin-deficientob/obmice exhibit a low-grade chronic inflammation together with a low muscle mass. Our aim was to analyze the changes in muscle expression levels of genes related to oxidative stress and inflammatory responses in leptin deficiency and to identify the effect ofin vivoleptin administration.Ob/obmice were divided in three groups as follows: controlob/ob, leptin-treatedob/ob(1 mg/kg/d) and leptin pair-fedob/obmice. Gastrocnemius weight was lower in controlob/obthan in wild type mice (P<.01) exhibiting an increase after leptin treatment compared to control and pair-fed (P<.01)ob/obanimals. Thiobarbituric acid reactive substances, markers of oxidative stress, were higher in serum (P<.01) and gastrocnemius (P=.05) of controlob/obthan in wild type mice and were significantly decreased (P<.01) by leptin treatment. Leptin deficiency altered the expression of 1,546 genes, while leptin treatment modified the regulation of 1,127 genes with 86 of them being involved in oxidative stress, immune defense and inflammatory response. Leptin administration decreased the high expression ofCrybb1, Hspb3, Hspb7, Mt4, Cat, Rbm9, Serpinc1andSerpinb1aobserved in controlob/obmice, indicating that it improves inflammation and muscle loss.