Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies

Abstract

Excess body weight is frequently associated with low-grade inflammation. Evidence indicates a relationship between obesity and cancer, as well as with other diseases, such as diabetes and non-alcoholic fatty liver disease, in which inflammation and the actions of various adipokines play a role in the pathological mechanisms involved in these disorders. Leptin is mainly produced by adipose tissue in proportion to fat stores, but it is also synthesized in other organs, where leptin receptors are expressed. This hormone performs numerous actions in the brain, mainly related to the control of energy homeostasis. It is also involved in neurogenesis and neuroprotection, and central leptin resistance is related to some neurological disorders, e.g., Parkinson’s and Alzheimer’s diseases. In peripheral tissues, leptin is implicated in the regulation of metabolism, as well as of bone density and muscle mass. All these actions can be affected by changes in leptin levels and the mechanisms associated with resistance to this hormone. This review will present recent advances in the molecular mechanisms of leptin action and their underlying roles in pathological situations, which may be of interest for revealing new approaches for the treatment of diseases where the actions of this adipokine might be compromised.

Diabetes Mellitus and Thyroid Cancers: Risky Correlation, Underlying Mechanisms and Clinical Prevention

“…The relationship between leptin and thyroid, liver, breast, lung, prostate, pancreatic, and colorectal cancer has been confirmed in many studies. 76 , 77 The leptin level in patients with diabetes is significantly higher than that in healthy individuals, and the leptin receptor is highly expressed in thyroid cancer cells. Therefore, high concentrations of leptin may promote the occurrence of thyroid cancer, indicating that an abnormal increase in leptin levels in patients with diabetes may be related to the occurrence and development of thyroid cancer.…”

The Role of Selected Adipocytokines in Ovarian Cancer and Endometrial Cancer

“…Leptin is the product of the LEP gene, located on chromosome 7. It is a peptide consisting of 167 amino acids, occurring as a tertiary protein structure, and has a molecular weight of 16 kDa [ 83 , 85 , 86 , 87 , 88 ]. While leptin is synthesized by adipocytes of adipose tissue, current reports indicate that leptin is also present in other tissues, including the placenta, mammary gland, ovary, skeletal muscle, stomach, and pituitary gland [ 85 ].…”

“…In addition, it stimulates αMSH (α-Melanocyte Stimulating Hormone) by stimulating POMC (Proopiomelanocortin), resulting in reduced food intake. Furthermore, leptin initiates cancer progression by affecting the initiation of signal transducers and activator of transcription 3 (STAT-3) and STAT-3 terminal gene expression resulting in melanocortin inhibition, stimulation of signal transducers and activator of transcription 5 (STAT-5), leading to altered gene expression, and stimulation of PI3K (Phosphatidylinositol-3-kinase), which interacts with insulin receptor pathways [ 88 , 92 , 93 , 94 ].…”

New Trends in Pathology: From Cell Morphology to Molecular Medicine

“…Another powerful molecule able to regulate fat metabolism is leptin, an adipokine mainly synthesised by adipose tissue. Casado et al reviewed the impact of leptin on the homeostasis of bone density and muscle mass [24]. Furthermore, the authors discussed central leptin resistance in neurological conditions, i.e., Parkinson's and Alzheimer's diseases.…”