Possible role of leptin in hypoandrogenicity in patients with systemic lupus erythematosus and rheumatoid arthritis

Abstract

Background: Hypoandrogenicity is common in obesity and in chronic inflammatory diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Adrenal androgens such as androstenedione (ASD) and dehydroepiandrosterone (DHEA) sulphate are low, which partly depends on the influence of TNF in chronic inflammatory diseases. Leptin is stimulated by TNF and is associated with hypoandrogenicity in non-inflammatory conditions. Objective: To study the interrelation between serum levels of leptin and adrenal steroids in SLE and RA. Methods: In a retrospective study, serum levels of leptin, ASD, DHEA, and 17-hydroxyprogesterone (17OHP) were measured by ELISA, and serum levels of cortisol by radioimmunoassay in 30 patients with RA, 32 with SLE, and 54 healthy control subjects (HS). Results: In SLE and RA but not HS, serum levels of ASD correlated negatively with serum levels of leptin (p,0.01) independently of prior prednisolone treatment in patients with SLE (p = 0.013) and tended to be independent of prednisolone in patients with RA (p = 0.067). In a partial correlation analysis, this interrelation remained significant after controlling for daily prednisolone dose in both patient groups. In both patient groups, serum leptin levels correlated negatively with the molar ratio of serum ASD/serum cortisol and serum ASD/serum 17OHP, and positively with the molar ratio of serum DHEA/serum ASD. Conclusions: The negative correlation of serum leptin and ASD or, particularly, ASD/17OHP, together with its known anti-androgenic effects indicate that leptin is also involved in hypoandrogenicity in patients with SLE and RA. Leptin may be an important link between chronic inflammation and the hypoandrogenic state.

Leptin in immuno-rheumatological diseases

“…Harle et al showed that leptin might provide an important link between chronic inflammation and the hypoandrogenic state in SLE patients. 63 Higher leptin concentrations in SLE patients, with respect to controls, have been reported by different authors, [64][65][66] suggesting a relationship between leptin and lupus disease-correlated factors. The same data have been recently reported in Korean SLE patients.…”

The impact of obesity on the musculoskeletal system

“…Leptin has been found to correlate negatively with adrenal androgen concentrations in patients with systemic lupus erythematosus and RA, suggesting that leptin may be an important link between chronic inflammation and the hypoandrogenic state. 155 Obesity and musculoskeletal disease A Anandacoomarasamy et al…”

“…Hypoandrogenicity in males is common in obesity and in chronic inflammatory conditions such as systemic lupus erythematosus and RA. 155 Leptin, as well reflecting adipose tissue mass, is stimulated by tumor necrosis factor and is associated with hypoandrogenicity in non-inflammatory conditions. Leptin has been found to correlate negatively with adrenal androgen concentrations in patients with systemic lupus erythematosus and RA, suggesting that leptin may be an important link between chronic inflammation and the hypoandrogenic state.…”

Cardiometabolic comorbidities and rheumatic diseases: Focus on the role of fat mass and adipokines

“…Low leptin levels associated with food restriction have been linked to CD4ϩ lymphocyte hyporeactivity and increased interleukin-4 (IL-4) secretion (35). Moreover, leptin has been involved in RA-induced hypoandrogenicity, since leptin levels were negatively correlated to androstenedione (36). Therefore, since leptin acts as a proinflammatory agent and androgens are generally considered as antiinflammatory molecules, the preponderance of leptin and hypoandrogenicity may help to perpetuate chronic rheumatic diseases such as RA.…”

“…Indeed, in a lupus animal model, both high-fat diet and leptin increase proinflammatory highdensity lipoproteins scores, atherosclerosis, and proteinuria, suggesting that factors typically associated with the metabolic syndrome can accelerate the disease and its cardiovascular complications (56). Moreover, leptin has been involved in SLE-induced hypoandrogenicity, since leptin levels were negatively correlated with androstenedione (36). In contrast to these studies, other groups have reported lower or unchanged circulating leptin levels in SLE patients compared to healthy controls (57,58).…”