The Emerging Role of Leptin Antagonist as Potential Therapeutic Option for Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) is a chronic relapsing immune-mediated inflammatory disorder that affects millions of people around the world. Leptin is a satiety hormone produced primarily by adipose tissue and acts both centrally and peripherally. Leptin has been shown to play a major role in regulating metabolism, which increases during IBD progression. Leptin mediates several physiological functions including elevated blood pressure, tumorogenesis, cardiovascular pathologies and enhanced immune response in many autoimmune diseases. Recent development of a leptin mutant antagonist that blocks leptin activity raises great hope and opens up new possibilities for therapy in many autoimmune diseases including IBD. To this end, preliminary data from an ongoing study in our laboratory on pegylated leptin antagonist mutant L39A/D40A/F41A (PEG-MLA) treatment shows an inhibition of chronic colitis in IL-10−/− mice. PEG-MLA effectively attenuates the overall clinical scores, reverses colitis-associated pathogenesis including a decrease in body weight, and decreases systemic leptin level. PEG-MLA induces both central and peripheral leptin deficiency by mediating the cellular immune response. In summary, after blocking leptin activity, the correlative outcome between leptin-mediated cellular immune response, systemic leptin levels, and amount of adipose tissue together may provide new strategies for therapeutic intervention in autoimmune diseases, especially for intestinal inflammation.

Peritonitis Incidence Was Correlated with Duration of Peritoneal Dialysis Rather than Leptin or Neutrophil to Lymphocyte (N/L) Ratio in Peritoneal Dialysis Patients

“…Leptin has also emerged as a potential mediator of inflammatory status and a positive modulator of IL-1α, TNF-α and IL-6 secretion. Leptin also increases IFN-γ, producing Th1 polarized cells and exerts its bioactivity at developmental, proliferation and activation levels [12][13][14][15]. In our study we detected that serum leptin level in peritoneal dialysis patients were significantly higher than in control group.…”

Peritonitis Incidence is Correlated with Increased Leptin and CD4/CD8 Ratio in Peritoneal Dialysis Patients

“…The mean serum leptin level of the patient group was statistically significantly higher than the control group (p<0.001). There was a statistically significant correlation between serum leptin level and duration of peritoneal also increases IFN-γ, producing Th1 polarized cells and exerts its bioactivity at developmental, proliferation and activation levels (15)(16)(17)(18). Although we did not detect a significant correlation between leptin and peritonitis incidence in our previous study (19), in the present study we detected that serum leptin levels of peritoneal dialysis patients were significantly higher than the control group.…”

Gastroduodenal Symptoms in Inflammatory Bowel Disease Are Correlated with Gastric Emptying and Serum Levels of Active Ghrelin

“…Before the test, patients and controls were instructed to avoid using any medications known to affect digestive motility (e.g., proton pump inhibitors, domperidone, or metoclopramide) or consuming a diet rich in 13C (e.g., corn flour and pineapples) [10] during the week before the test. After an overnight fast, each patient received a 250 kcal meal consisting of 60 g white bread, 5 g margarine, and 1 egg (the yolk of which was labeled with 100 mg of 13C octanoic acid and sodium salt).…”

“…Besides, along with blocking leptin activity, the correlations among leptin-mediated cellular immune response, systemic leptin levels, and amount of adipose tissues may provide new strategies for therapeutic intervention in autoimmune diseases, especially for intestinal inflammation [10].…”