Immuno-modulator metallo-Peptide reduces inflammatory state in obese zucker fa/fa rats

Abstract

Metabolic syndrome is a prothrombotic and proinflammatory chronic state. In obesity, the adipose tissue secretes various adipokines that take part in a variety of physiological and pathophysiological processes, including immunity and inflammation. Previous studies using a liver damage model treated with the immune-modulator metallo-peptide (IMMP) showed lessening in the degree of inflammation. Therefore, this study was set up to evaluate the anti-inflammatory effect of IMMP in obese Zucker fa/fa rats. We used Zucker-Lepr fa/fa and Zucker-Lean in this protocol. The groups received IMMP 50 ng/kg by i.p., three times per week for 8 weeks. Blood samples were collected by cardiac puncture and the serum was preserved at -80°C until analysis; the liver was excised and preserved in formaldehyde 4%. Analyses were performed to determine cytokine, insulin, glucose, triglyceride and cholesterol levels in serum, and histological analysis was also performed. IMMP treatment of obese rats resulted in decreased levels of proinflammatory cytokines (leptin, lL-6, IL-1betha, INF-gamma) and a chemokine (MCP-1), and increased levels of anti-inflammatory adipokine (adiponectin). In addition, treatment decreased the damage and hepatic steatosis generated in the tissue of obese rats. The IMMP exerted an anti-inflammatory effect in obese rats and therefore may be an effective and safe therapeutic alternative in the treatment of metabolic syndrome.

Keywords: Immunomodulator; Inflammation; Metabolic syndrome; Obesity; Peptide.

Figure 1

Effect of IMMP on adipokine levels in the serum of lean and obese rats treated during 8 weeks. A, Leptin; B, Adiponectin. The results are presented as mean ± S.D. from 5 animals in each group. ^* p<0.05 compared with Lean group; ^# p<0.05 compared with Obese group.

Figure 2

Effect of IMMP on proinflammatory cytokine levels in the serum of lean and obese rats treated during 8 weeks. A, IL-6; B, TNF-α; C, INF-γ and D, IL-1β. The results are presented as mean ± S.D. from 5 animals in each group. ^* p<0.05 compared with lean group; ^# p<0.05 compared with obese group.

Figure 3

Effect of IMMP on MCP-1 levels in the serum of lean and obese rats treated during 8 weeks. The results are presented as mean ± S.D. from 5 animals in each group. ^* p<0.05 compared with lean group; ^# p<0.05 compared with obese group.

Figure 4

Effect of IMMP on anti-inflammatory cytokine levels in the serum of lean and obese rats treated during 8 weeks. A, IL-10; B, IL-4. The results are presented as mean ± S.D. from 5 animals in each group. ^* p<0.05 compared with lean group; ^# p<0.05 compared with obese group.

Figure 5

Effect of IMMP on the morphology of the liver. Liver slice A, Lean; B, Lean+IMMP; C, obese and D, obese+IMMP after 8 weeks of evaluation. Hematoxylin and Eosin staining, magnification × 40. P, Portal; HA, Hepatic artery; BC, bile duct; Circle, lipid vacuoles; Arrows, polymorphic nuclei.