**10. Leptin therapeutics past and future**

The significant need for clinical implications of leptin is to regulate the regular physiological role of leptin in pathological conditions. There is a correlation between

### *Biodiversity of the Adipocyte-Derived Hormone, Leptin DOI: http://dx.doi.org/10.5772/intechopen.100576*

body weight loss and serum levels of leptin. As a result, several therapeutic approaches have been implemented for the use of leptin in obesity control. However, increased resistance to leptin is also a significant issue in the treatment of obesity. But, a combination of therapeutic approaches may be helpful to these problems [112, 113].

Among the adipocyte secreted hormones, leptin is the front that has been used for the treatment of hypoleptinemia status clinically. The most important therapeutic benefits of leptin are rely on providing a novel method for treating the conditions connected with mutation of leptin gene and lipodystrophy in humans [114]. Treatment with exogenous leptin in obese patients concluded that leptin can decrease the body weight and fat tissue of the subjects [115]. It was also noted that leptin excerpts a dose-dependent regulating potential as individuals energy intake and appetite [116, 117]. Development of leptin analogous with full biological effect, especially with the potential to cross the blood–brain barrier, can improve the results obtained from leptin therapy focusing on obesity management. The administration of leptin can accelerate wound healing in diabetic ob/ob and wild-type mice in a dose-dependent manner through leptin receptor mediation [118].

Exogenous administration of leptin can regulate fatty acid oxidation in muscles and control triglyceride synthesis in the liver [119, 120]. Even though the mechanisms in humans are not clear, administration of leptin and adiponectin was found to improve insulin resistance in type 2 diabetic conditions [121, 122]. The immunemodulatory impact of exogenous leptin administration in rodents highlighted that the cytokine could activate encephalomyelitis [123]. Various in vitro assays also supported the immune stimulator action of leptin [124, 125]. Identifying high-affinity-binding molecules to control the level of circulating leptin is suggested as an advanced therapy for treating arthritis and inflammatory bowel disease. In addition, replacement with recombinant methionyl human leptin is a brilliant choice for treating pathological conditions associated with relative or absolute leptin deficiency and restoring immune functions [126]. One of the future therapeutic approaches of leptin relies on its use as a natural adjuvant in vaccinations since it can stimulate T helper I responses while down-modulating regulatory T cells [127].

Considering the cancerous conditions, ATLO-ACA, an Ob-R antagonist peptide, finds effective for treating triple-negative breast cancers in experimental models [128]. Also, therapy based on leptin/Ob R axis function inhibition was identified as adjunctive therapy for newly diagnosed and recurrent glioblastoma [129]. The modern therapeutic approaches of leptin are connected with molecular approaches at gene levels are 1) CRISPR-Cas 9 connected with floxed leptin-locus based approaches - to lower the leptin levels, 2) Cre-lox P- generation of one copy of Lep eliminates – to lower the leptin levels, glucose and insulin tolerance, c) administration of neutralizing leptin-specific antibodies –to reduce the circulating levels of leptin to reduce food intake and hepatic stenosis [130]. Administration of human recombinant leptin accelareated dose-dependent sprouting angiogenesis and hypothesized that the application of human recombinant leptin could improve the wound healing process through neovascularization [3]. So far, evidence gathered from previous studies highlights the role of leptin in therapeutic applications. But overcoming leptin resistance is a significant challenge in leptin-based therapy.
