The Mystery behind the Pineal Gland: Melatonin Affects the Metabolism of Cholesterol

Abstract

Melatonin may be considered a cardioprotective agent. Since atherogenesis is partly associated with the metabolism of lipoproteins, it seems plausible that melatonin affects cardiovascular risk by modulating the metabolism of cholesterol and its subfractions. Moreover, cholesterol-driven atherogenesis can be hypothetically reduced by melatonin, mainly due to the minimalization of harmful reactions triggered in the cardiovascular system by the reactive oxygen species-induced toxic derivatives of cholesterol. In this review, we attempted to summarize the available data on the hypolipemizing effects of melatonin, with some emphasis on the molecular mechanisms underlying these reactions. We aimed to attract readers’ attention to the numerous gaps of knowledge present in the reviewed field and the essential irrelevance between the findings originating from different sources: clinical observations and in vitro mechanistic and molecular studies, as well as preclinical experiments involving animal models. Overall, such inconsistencies make it currently impossible to give a reliable opinion on the action of melatonin on the metabolism of lipoproteins.

Impact of Melatonin Deficit on Emotional Status and Oxidative Stress-Induced Changes in Sphingomyelin and Cholesterol Level in Young Adult, Mature, and Aged Rats

“…Cholesterol, with its functional pleiotropism can play a major role in the regulation of neuronal functions and toxic cholesterol derivatives, which are formed with the participation of reactive oxygen species and become harmful factors for different neurodegenerative pathologies in the elderly [ 7 ]. Since the reports suggest that melatonin could be an effective cholesterol stabilizer in animal models of hypercholesterolemia [ 8 ], we can assume that melatonin, and its deficiency, might be a beneficial regulator of cholesterol concentration.…”

Melatonin Attenuates ox‐LDL‐Induced Endothelial Dysfunction by Reducing ER Stress and Inhibiting JNK/Mff Signaling

“…Among these risk factors, endothelial cells are particularly vulnerable to ox-LDL-induced stress through unknown mechanisms [6][7][8]. Increases in ox-LDL result in decreased proliferative ability, impaired migratory response, increased apoptotic index, and reduced regenerative capability in endothelial cells [9][10][11]. Although many studies have examined the relationship between ox-LDL and pathological alterations in endothelial cells in vivo and in vitro, the key molecular mechanisms underlying ox-LDL-associated endothelial dysfunction have not been fully explained, and few effective therapeutic drugs are available for patients with endothelial dysfunction.…”

Melatonin Levels in Children with Obesity Are Associated with Metabolic Risk and Inflammatory Parameters

“…The associations found between the night melatonin and these different factors could support the hypothesis of a potential atheroprotective role of melatonin which is increased to counteract the atherogenic effects of obesity. Whereas animal models provide evidence of the beneficial regulation of cholesterol by exogenous melatonin [ 34 ], clinical observations mainly failed to find a protective effect [ 35 , 36 , 37 , 38 ]. Although this difference may be explained by the high interindividual variability in the bioavailability of melatonin in humans [ 39 ], such inconsistencies make it difficult to give a reliable opinion on the action of melatonin on the metabolism of lipoproteins.…”