Adipose tissue, serum adipokines, and ghrelin in patients with ankylosing spondylitis
Introduction
Ankylosing spondylitis (AS) is a chronic inflammatory disease that mainly affects the axial skeleton. Weight loss is observed during acute and chronic inflammatory processes and may influence physical activity, quality of life, and also survival. Indeed, changes in body composition and particularly lean mass have been described in rheumatic diseases, mainly rheumatoid arthritis (RA) [1] and systemic lupus erythematosus [2]. These changes were related to increased levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF) α, interleukin (IL) 1, or IL-6 [1].
Inflammatory cytokines are produced by different cell subtypes, circulating monocytes, or lymphocytes, but can also have other cellular sources such as macrophages from fat tissue. Indeed, adipose tissue is no longer considered as an inert tissue devoted to energy storage, but is also an active participant regulating physiologic and pathologic processes including immunity and inflammation [3], [4]. Besides the production of classic cytokines, fat tissue, and notably adipocytes, produced and released itself certain proteins or adipokines [4]. Leptin and adiponectin are 2 of these adipokines, and their biological functions have been well characterized [5], [6]. Indeed, leptin has a wide range of biological properties including the regulation of food intake, energy expenditure, and also immunity. Leptin is rather considered as a proinflammatory molecule linking fat tissue to the cells participating in the inflammatory response [5], [7]. Conversely, leptin may also possess anti-inflammatory properties [8]. Adiponectin is best known for its role in the regulation of insulin sensitivity and acts as an insulin-sensitizing hormone with reduced blood concentration in obesity, metabolic syndrome, and type 2 diabetes mellitus. On the other hand, adiponectin is considered as an anti-inflammatory molecule by reducing the activity and the production of cytokines such as TNF-α [5], [9]. In addition, leptin and adiponectin have been implicated in experimental models of inflammation and in human diseases such as RA, multiple sclerosis, or asthma [5].
Ghrelin is a recently described growth hormone (GH)–releasing molecule produced by the stomach. It induces a positive energy balance by stimulating appetite. It also has antagonist effects on leptin through hypothalamic pathway and thus has potential influences in the regulation of weight. In addition, interaction between ghrelin and immune cells has recently been described [10].
Thus, adipose tissue must be currently considered as an active tissue producing molecules involved in the control of appetite and also in the regulation of inflammatory responses. In this study, we aimed at evaluating adipose tissue in patients with AS to examine the contribution of fat-derived molecules to the inflammatory response. Thus, circulating levels of leptin, adiponectin, and also ghrelin were evaluated; and we examined the relationships between these molecules and disease activity. Anabolic hormones such as GH and insulin growth hormone I (IGF-I) were assessed because of their interrelations with leptin, ghrelin, and body composition [11].
Section snippets
Patients
Fifty-three white outpatients consecutively seen in our department were included. They all responded to the modified New York criteria [12]. Clinical assessments included demographic data, as follows: age, sex, weight and height, body mass index (BMI; weight [in kilograms] divided by height [in meters] squared), disease duration, and extraarticular manifestations (history of uveitis). The clinical activity was evaluated using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [13]
Adipose tissue
A total body scan was performed using a Lunar DPX-IQ densitometer (Lunar, Madison, WI). Measurements were given for body composition from the total body scan with fat mass (in grams) and lean mass (also in grams). The reproducibility of total body measurements was 0.7%.
Results
The demographics, clinical characteristics, and inflammatory markers of the studied patients are listed in Table 1. Patients and controls did not differ for age, sex ratio, BMI, levels of physical activity, and dietary intake. The CRP levels and ESR were significantly higher in patients compared with those in controls (P < .005), whereas serum TNF-α did not differ between the 2 groups.
We found no significant differences in fat mass and lean mass between patients and controls (all Ps > .05,
Discussion
Our results show that our AS patients had no changes in adipose tissue compared with controls and no changes in serum adiponectin in contrast with decreased serum leptin and increased ghrelin levels in male patients. In addition, IGFBP-3 levels were also decreased in our patients.
In inflammatory rheumatic diseases, chronic inflammation is associated with weight loss by the production of different mediators and particularly inflammatory cytokines that induce tissue damage, protein catabolism,
Acknowledgment
This work was supported by a grant from l'Association Franc-Comtoise pour la Recherche et l'Enseignement en Rhumatologie.
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