BRIEF REPORT Inflammatory State and Stress Condition in Weight-lowering Lys109Arg LEPR Gene Polymorphism Carriers Iztiar Abete, Estı ´baliz Goyenechea, Ana Belen Crujeiras, and J. Alfredo Martı ´nez Department of Nutrition, Food Science, Physiology and Toxicology, University of Navarra, Pamploma, Spain Received for publication November 24, 2008; accepted March 2, 2009 (ARCMED-D-08-00537). Previously published online June 5, 2009. Background and Aims. Carrying variants on the leptin receptor gene (LEPR) may have an impact on inflammatory and stress markers. Thus, the aim of the study was to analyze the role of the Lys109Arg LEPR gene polymorphism on inflammatory (leptin and IL-6) and stress (cortisol) markers in obese subjects who followed a hypocaloric diet designed to lose weight. Methods. One hundred and seventy (80 females/90 males) Caucasian subjects (body mass index: 30.8  2.4 kg/m 2 ), were genotyped for the Lys109Arg polymorphism by a PCR/RFLP procedure. Anthropometric measurements were assessed and blood samples were drawn in all the volunteers before and after an 8-week energy-restricted diet (30% E). Plasma levels of leptin as well as interleukin-6 (IL-6) as proinflammatory markers and circulating cortisol concentrations as a stress hormone were measured. Results. Weight loss (6.1  2.7%; p !0.001) induced significant changes in anthro- pometric and biochemical determinations. The AA genotype group showed a higher fat mass loss as well as greater total cholesterol decrease compared with the minor allele carriers. Moreover, the G allele carriers were associated with a higher basal risk of inflammation (OR 5 2.5; p 5 0.042) and stress (OR 5 3.3; p 5 0.011), which were reduced after weight lowering ( p O0.05). Conclusions. The Arg allele carriers of the Lys109Arg LEPR gene polymorphism were associated with an increased proinflammatory state and stress condition at baseline. These obesity-related markers were importantly decreased after following a hypocaloric diet. Ó 2009 IMSS. Published by Elsevier Inc. Key Words: Lys109Arg, Leptin receptor polymorphism, IL-6, Cortisol, Obesity. Introduction Obesity has been associated with a low-grade proinflamma- tory state, which is accompanied by an increase on the secretion of some cytokines (1). Thus, high IL-6 and leptin levels have been related not only to a high body mass index (BMI), but also to type 2 diabetes, lipid abnormalities and high blood pressure (2), which are common comorbidities found in obese subjects. In this context, it is also known that environmental stress can produce a progressive dysfunction of the hypothalamic/pituitary/adrenal axis and increases in cortisol levels (3). Indeed, over the last decade, a cons- iderable amount of evidence has emerged regarding the pathogenic role of cortisol in obesity, in addition to the known anti-inflammatory properties of glucocorticoids (4). Furthermore, several studies suggest that leptin has proin- flammatory and stress effects that may link an increased adipose mass directly to cardiovascular risk factors (5,6). In this regard, genetic variants affecting the function of the leptin receptor could have an impact on the levels of adipokines as well as on inflammatory and stress markers (4,7,8). To investigate these issues, we conducted a trial to assess the role of the Lys109Arg LEPR gene polymor- phism on the inflammation state and the stress condition in the obese as well as on the putative relationships of inflammatory and stress markers with body weight and biochemical changes after following a hypocaloric nutri- tional intervention. Address reprint requests to: Prof. J. Alfredo Martı ´nez, Dept. of Nutri- tion and Food Science, Physiology and Toxicology, University of Navarra, C/Irunlarrea 1, 31008 Pamplona, Spain; E-mail: jalfmtz@unav.es 0188-4409/09 $esee front matter. Copyright Ó 2009 IMSS. Published by Elsevier Inc. doi: 10.1016/j.arcmed.2009.03.005 Archives of Medical Research 40 (2009) 306e310