Endocrinologie et syndrome métabolique
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Role of Leptin in Immune Dysfunction in WNIN Obese Rats

Prathibha Bandaru, Hemalatha Rajkumar, Venkata Prasad Upadrasta and Giridharan Nappanveettil

Aim: Role of leptin in bringing about systemic immune response under obesity has so far been speculative. In the present study we addressed this question using genetically obese rats developed at our centre- WNIN/Ob and WNIN/ GR-Ob.

Methodology: Both the lean (+/+) and homozygous obese animals (-/-) received either phosphate buffered saline or leptin. While another set of fed lean and obese served as controls. Effect of leptin on immune function was assessed in terms of splenic lymphocyte proliferative response to Concavalin A (Con A), splenic CD4/CD8 ratio and Nitric oxide (NO) production by macrophages. Further, we also studied if the effect of leptin on immune function was associated with changes in receptor OBR (Leptin receptor) and or JAK2 (Janus tyrosine kinase 2) total protein expression.

Results: Lean animals of both the strains (WNIN/GR-Ob & WNIN/Ob lean) responded to leptin treatment, in terms of increased CD4/CD8 ratio and lipopolysaccharide stimulated peritoneal macrophage Nitric Oxide (NO) production (P<0.05), while splenic lymphocyte proliferative response (P<0.05) to Concavalin A upon leptin treatment was observed only in WNIN/GR-Ob lean animals. Furthermore, significant increase in obese receptor (OBR) protein expression and a trend for JAK2 protein expression (P=0.06) upon leptin treatment were seen in WNIN/GR-Ob and WNIN/Ob lean animals respectively.

Conclusion: The data thus show that leptin resistance could be one of the factors associated with immune dysfunction in obese condition.