Hindawi Publishing Corporation Mediators of Inﬂammation Volume 2010, Article ID 784343, 15 pages doi:10.1155/2010/784343 Research Article Leptin Administration Downregulates the Increased Expression Levels of Genes Related to Oxidative Stress and Inﬂammation in the Skeletal Muscle of ob/ob Mice Neira S ´ ainz, 1, 2 Amaia Rodr´ ıguez, 1, 2 Victoria Catal ´ an, 1, 2 Sara Becerril, 1, 2 Beatriz Ram´ ırez, 1, 2 Javier G ´ omez-Ambrosi, 1, 2 and Gema Fr ¨ uhbeck 1, 2, 3 1 Metabolic Research Laboratory, Cl´ ınica Universidad de Navarra 3, 31008 Pamplona, Spain 2 CIBER Fisiopatolog´ ıa de la Obesidad y Nutrici´ on (CIBEROBN), Instituto de Salud Carlos III, Spain 3 Department of Endocrinology, Cl´ ınica Universidad de Navarra, P´ ıo XII 36, 31008 Pamplona, Spain Correspondence should be addressed to Gema Fr¨ uhbeck, gfruhbeck@unav.es Received 21 January 2010; Revised 31 March 2010; Accepted 24 April 2010 Academic Editor: Giamila Fantuzzi Copyright © 2010 Neira S´ ainz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Obese leptin-deﬁcient ob/ob mice 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 of in vivo leptin administration. Ob/ob mice were divided in three groups as follows: control ob/ob, leptin- treated ob/ob (1 mg/kg/d) and leptin pair-fed ob/ob mice. Gastrocnemius weight was lower in control ob/ob than in wild type mice (P<.01) exhibiting an increase after leptin treatment compared to control and pair-fed (P<.01) ob/ob animals. Thiobarbituric acid reactive substances, markers of oxidative stress, were higher in serum (P<.01) and gastrocnemius (P = .05) of control ob/ob than 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 of Crybb1, Hspb3, Hspb7, Mt4, Cat, Rbm9, Serpinc1 and Serpinb1a observed in control ob/ob mice, indicating that it improves inﬂammation and muscle loss. 1. Introduction Obesity is associated with a low-grade proinﬂammatory state resulting in an increase of circulating cytokines and inﬂam- matory markers [1]. Inﬂammatory cytokines have been involved in the impairment of insulin signaling, thus provid- ing molecular links between inﬂammation and insulin resis- tance [2]. Inﬂammation reportedly produces metabolic alter- ations in skeletal muscle with both inﬂammatory response and insulin resistance being associated with loss of muscle mass by decreased protein synthesis and increased proteolysis [3–5]. Recently, our group has shown that leptin reverses muscle loss of ob/ob mice by inhibiting the activity of the transcriptional factor forkhead box class O3a (FoxO3a) [6]. Leptin is an adipocyte-derived peptidic hormone [7] that inhibits food intake and increases thermogenesis by acting through its hypothalamic receptors [8, 9]. Leptin-deﬁcient ob/ob mice are obese, hyperphagic, exhibit type 2 diabetes, decreased body temperature and hypogonadotropic hypog- onadism [10]. Leptin is a member of the long-chain helical cytokine family and its receptors, which belong to the class I cytokine receptors, are present in bone marrow and spleen as well as on peripheral monocytes and lymphocytes [1]. Leptin increases in response to acute infection and sepsis and it has been reported to exert a profound inﬂuence on the function and proliferation of T lymphocytes and natural killer cells [11], on the phagocytosis of macrophages/monocytes [12], and to have a direct eﬀect on the secretion of anti- and proinﬂammatory cytokines [13]. In this regard, impaired cellular and humoral immunity have been shown in leptin- deﬁcient ob/ob mice as well as in leptin receptor-deﬁcient db/db mice [14, 15]. These studies reﬂect the molecular nature of leptin as a cytokine and are consistent with leptin signaling playing a pivotal role in the pathogenesis of obesity- associated inﬂammation and muscle loss.