Metabolic Syndrome, its Pathophysiology and the Role of Melatonin
Venkataramanujam Srinivasan, Yoshiji Ohta, Javier Espino, Jose A. Pariente, Ana B. Rodriguez, Mahaneem Mohamed and Rahimah Zakaria
Affiliation: Sri Sathya Sai Medical Educational and Research Foundation, Prasanthi Nilayam, 40-Kovai Thirunagar, Coimbatore-641014, Tamilnadu, India.
Metabolic syndrome (MetS) is characterised by symptoms of obesity, insulin resistance, hypertension, dyslipidemia
and diabetes mellitus. The pathophysiological mechanisms involved in MetS are complex and involved dysregulation
of many biochemical and physiological regulatory mechanisms of the body. Elevated levels of low density lipoproteins
like VLDL, and LDL with reduction of HDL seen in patients with MetS contribute to atherogenic dyslipedemia.
Melatonin has been suggested to be effective in improving MetS through its anti-hyperlipidemic action. Melatonin reduced
both adiposity, and body weight in experimental animal studies and also attenuated weight gain and obesityinduced
metabolic alterations and this effect of melatonin is attributed to its anti-oxidative effects. Melatonin administration
has been shown to inhibit insulin release by acting through both MT1 and MT2 melatonin receptors present in pancreatic
β-cells. Melatonin also increased insulin sensitivity and glucose tolerance in animals fed with either high fat or high
sucrose diet. Melatonin exerts most of its beneficial actions by acting through MT1 and MT2 melatonin receptors present
in various tissues of the body and some of the metabolic actions of melatonin have been blocked by melatonin antagonist
like luzindole. Ramelteon, the newly available melatonin agonist will also have more promising role in the control of
MetS. The numbers of patents are available with regard to treatment of MetS. Drug related to antidepressant fluoxetine is
used for treatment of MetS (US Patent No. 2008001400450). Anti-oxidants like S-adenosyl-methionine, Vitamin E, and
Vitamin C have been found beneficial in treating MetS (US Patent No. 8063024). Melatonin being a powerful Antioxidant
will have a promising role in treating patients with metabolic syndrome.
Keywords: Diabetes, hypertension, insulin resistance, melatonin, metabolic syndrome, obesity, adipokines, vascular dysfunction, vascular function abnormalities, ghrelin
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