Leptins in Obesity, Diabetes and Metabolic Pathologies: An Overview

Excess body weight is intricately linked to low-grade inflammation, establishing a significant association between obesity and various diseases, including cancer, diabetes, and non-alcoholic fatty liver disease. The interplay of inflammation and adipokines contributes to the pathological mechanisms underlying these conditions. Leptin, primarily synthesized by adipose tissue in proportion to fat stores, is also produced in organs such as stomach, placenta and mammary glands, expressing leptin receptors. While its primary role involves actions related to energy homeostasis, neurogenesis, and neuroprotection, leptins have metabolic role in peripheral tissues, impacting metabolism, bone density, and muscle mass. Changes in leptin levels and mechanisms associated with leptin resistance can influence these mechanisms presenting a complex landscape.

Despite its potential as a treatment for obesity due to its capacity to reduce food intake and body weight, leptin faces challenges in clinical and pharmaceutical application. Obesed individuals exhibit elevated leptin resistance to exogenous administration, termed leptin resistance and it limits its anorexigenic effects. The molecular mechanisms that are responsible for leptin resistance remain incompletely characterized, posing obstacles to therapeutic interventions. Leptin's journey across the blood-brain barrier to reach the hypothalamus, where it exerts anorexigenic functions, adds another complexity to its clinical implementation. Recent strategies aim to restore leptin responsiveness in obesity, encompassing approaches such as leptin sensitization, combination therapies, and direct modulation of intracellular signaling. Understanding and targeting leptin resistance holds promise for innovative approaches to treat obesity and associated metabolic disorders effectively. Ongoing research endeavors seek to unravel leptin's complexities and pave the way for novel therapeutic interventions in obesity and its related health implications.