Abstract
Deficiency of leptin (ob/ob) and/or desensitization of leptin signaling (db/db) and elevated expression of suppressor of cytokine signaling-3 (SOCS3) reported in obesity are also reported in a variety of pathologies including hypertriglyceridemia, insulin resistance, and malnutrition as the risk factors in host defense system. Viral infections cause the elevated SOCS3 expression, which inhibits leptin signaling. It results in immunosuppression by T-regulatory cells (Tregs). The host immunity becomes incompetent to manage pathogens' attack and invasion, which results in the accelerated infections and diminished vaccine-specific antibody response. Leptin was successfully used as mucosal vaccine adjuvant against Rhodococcus equi. Leptin induced the antibody response to Helicobacter pylori vaccination in mice. An integral leptin signaling in mucosal gut epithelial cells offered resistance against Clostridium difficile and Entameoba histolytica infections. We present in this review, the intervention of leptin in lethal diseases caused by microbial infections and propose the possible scope and challenges of leptin as an adjuvant tool in the development of effective vaccines.
Highlights
Leptin and Leptin ReceptorsLeptin was discovered as the product of obese gene (Zhang et al, 1994), which is located on the long arm of 7th chromosome at the position 31.3 (7q31.3) of about ∼20 Kb length (Considine and Caro, 1997)
Ob-Ra and Ob-Rc isoforms regulate the transportation of leptin across the blood-brain barrier (BBB) to hypothalamus and Ob-Rf performs the same function to a lesser extent
Pulmonary bacterial load during S. pneumonia infection in leptin-deficient individuals results in the failure of host defense system, which is associated with abundant production of tumor-necrosis factor (TNF)-α, macrophage inflammatory peptide (MIP)2 and prostaglandin-E2 (PGE2) in the lung tissue
Summary
Leptin was discovered as the product of obese (ob) gene (Zhang et al, 1994), which is located on the long arm of 7th chromosome at the position 31.3 (7q31.3) of about ∼20 Kb length (Considine and Caro, 1997). The nascent non-glycosylated protein has a M.W. 16 kDa, with an NH2 terminal signal peptide (21-amino acids). Active form of leptin is 146 amino acids peptide. Leptin receptor gene (Ob-R) comprises four short-isoforms (Ob-Ra, Rc, Rd, and Rf ), one long-isoform (Ob-Rb) and one soluble-isoform (Ob-Re) (Tartaglia, 1997). Six isoforms of Ob-R are identical to each other and contain 805 amino acids and 1–14 exons present in extracellular domain. Ob-Rb isoform consist of long intracellular domain that resembles the type-I cytokine receptor signaling domain and transduces via Janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT) pathway (Houseknecht and Portocarrero, 1998; Licinio et al, 1998). Most of the biological functions of leptin are exerted by Ob-Rb-JAK/STAT signaling cascade, which is present predominantly in hypothalamus but has moderate presence in other tissues.
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