The Important Role of Leptin in Modulating the Risk of Dermatological Diseases

Abstract

It is an indisputable fact that obesity is associated with a series of health problems. One important hallmark of obesity is excessive accumulation of lipids in the adipocyte, especially triglyceride (TG). Currently, the adipocyte has been considered not only as a huge repository of excess energy in the form of fat but also as an important source of multiple hormones and cytokines called adipokines. In obesity, the adipocyte is dysfunctional with excessive production and secretion of pro-inflammatory adipokines, such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and leptin. On the other hand, accumulating evidence has shown that leptin plays a vital role in stimulating angiogenesis, controlling lipid metabolism, and modulating the production of pro-inflammatory cytokines. Furthermore, the various activities of leptin are related to the wide distribution of leptin receptors. Notably, it has been reported that enhanced leptin levels and dysfunction of the leptin signaling pathway can influence diverse skin diseases. Recently, several studies revealed the roles of leptin in wound healing, the hair cycle, and the pathogenic development of skin diseases, such as psoriasis, lupus erythematosus, and dermatological cancers. However, the exact mechanisms of leptin in modulating the dermatological diseases are still under investigation. Therefore, in the present review, we summarized the regulatory roles of leptin in the pathological progression of diverse diseases of skin and skin appendages. Furthermore, we also provided evidence to elucidate the complicated relationship between leptin and different dermatological diseases, such as systemic lupus erythematosus (SLE), psoriasis, hidradenitis suppurativa, and some skin tumors.

Exploring the Links between Obesity and Psoriasis: A Comprehensive Review

“…Moreover, a biologic may offer the most effective treatment for many people with moderate-to-severe psoriasis or psoriatic arthritis. These drugs target four different immune signalling pathways: (1) TNF-α inhibitors [116], such as adalimumab, certolizumab pegol, etanercept, infliximab and golimumab (2). IL-17 inhibitors, such as brodalumab, ixekizumab, and secukinumab.…”

“…T helper cells, mast cells and neutrophils produce IL-17, which triggers the production of cytokines and chemokines in keratinocytes through an anticipant inflammatory response [ 39 ]. This process is accompanied by angiogenesis [ 2 , 121 ] and occurs at the level of the mainly visceral white adipose tissue that functions as an endocrine organ [ 40 ]. In psoriasis, the direct pathogenic cells are epidermal keratinocytes, inflammatory T cells, antigen-presenting cells, and dysregulation in the innate and adaptive immune system [ 33 ].…”

“…Obesity is a highly prevalent, chronic, and multifactorial endocrine-metabolic disease characterised by an excessive increase in body weight due to abnormal accumulation of body fat [ 1 ]. In this regard, the Metabolically Unhealthy Obese phenotype (MUO) is associated with cardiovascular [ 2 , 3 , 4 ], osteoarticular [ 5 ], hepatobiliary [ 6 ], psychological [ 7 ], neurological [ 8 ], and immune system diseases [ 9 ], besides some forms of cancer [ 10 ]. In this context, obesity is considered a public health issue of significant scale and a challenge for healthcare systems considering its complex management and the economic impact of its comorbidities [ 11 , 12 ].…”

Active Tumor-Targeting Nano-formulations Containing Simvastatin and Doxorubicin Inhibit Melanoma Growth and Angiogenesis

“…We further showed that the drastic reduction in tumor growth induced by the combined sequential therapy was accompanied by a highly potent suppression of TME angiogenic capacity ( Figures 4 , 5 ; Table 4 ; Supplementary Figure S2 ). This was based on strong inhibitory actions (>90%) on VEGF (major angiogenesis coordinator), FasL (inducer of anticancer T-cell apoptosis at the vascular border), and leptin (stimulator of angiogenesis and overall accelerator of melanoma growth) ( Figures 4 , 5A ,C; Table 4 ) ( Apte et al, 2019 ; Su et al, 2020 ). In addition, the expression level of the CD31 marker of endothelial cell proliferation was also strongly inhibited ( Figures 5A,B ) and the macrophage density in melanoma tissue was significantly reduced in both IL-13-LCL-SIM and combination therapy groups, indicating an IL-13-LCL-SIM-mediated suppression of angiogenesis-promoting function of TAMs ( Figures 5A,D ).…”

Biodiversity of the Adipocyte-Derived Hormone, Leptin

“…Leptin could accelerate the proliferation process in native CD4 + T cells and favored by reducing the levels of IFN from T cells [43,44]. During the wound healing process, leptin activates both inflammatory and proliferative phases in favor of tissue repair [45]. The increased plasma leptin level acts as an indicator of leptin-induced inflammatory response at the injury site.…”