Biological time keeper linked to diabetes and obesity
BIOLOGICAL TIME KEEPER LINKED TO DIABETES AND OBESITYIn mammals, melatonin is synthesized mainly by the pineal gland but is also formed by many otherorgans and tissues in the body. It is synthesized from serotonin, and therefore ultimately fromtryptophan. It is released from the pineal gland in response to darkness (its levels are high during thenight and low during the day).The human pineal gland is most active in our youth, just before puberty after which it seems to calcifywithout diminishing the production of melatonin.Melatonin is involved in the control of various physiological functions of the body, such as co-ordinationof circadian rhythms, sleep regulation, immune function, anti-oxidant functions, control of reproduction,inhibition of tumor growth, and the control of human mood and behavior.Melatonin regulates many of these functions indirectly, by acting through G-protein membranereceptors (MT1 and MT2 melatonin receptors). It also acts directly on cells without the intervention ofreceptors by binding to calmodulin.Melatonin diffuses through all tissues with ease. CSF melatonin levels are nearly 30 times higher thanthose in the blood. Brain tissue has higher melatonin concentrations than any other tissue in the body(1).Melatonin has been shown to have beneficial effects in cardiovascular disorders including ischemicheart disease and hypertension (2). It is also an interesting neuroprotective agent as it displays multipleproperties through which it antagonizes oxidativestress and counters neurodegeneration.
Aside from its own neuroprotective action, in the brain melatonin is metabolized into otherneuroprotective compounds such as the kynuramines(3).Recent studies of astrocytes show that astrocytic apoptosis contributes to the pathogenesis ofAlzheimer’s disease (AD). Astrocytes not only exhibit tau phosphorylation and activation of stresskinases, but by interacting with Aβ peptides, astrocytes lose control over glial NO production, therebyforming neurotoxic peroxynitrate. Melatonin was shown to reverse these neurodegenerative changes(4).Melatonin seems to inhibit neurodegeneration at many levels, as shown in this graph:Melatonin inhibits amyloid-β protein deposition, inhibits formation of amyloid fibrils, scavenges free radicals induced byamyloid β protein, prevents cytoskeletal disorganization and inhibits lipid peroxidation reactions in neural tissues.Melatonin and MetabolismNew data show that melatonin may play an important role in body weight regulation and energymetabolism, making it a potential therapeutic tool to prevent or reverse the harmful effects of obesity.Microdeletion of chromosome 16 is a new cause of obesity which may explain about 1% of obesitycases. This defect leads to the suppression of about thirty genes in one region of chromosome 16,amicrodeletionrelatively common in obese people (5).The gene on chromosome 16, encoding the melatonin-related receptor (GPR50), is highly expressedwithin hypothalamic nuclei concerned with the control of body weight (6).Melatonin up-regulates consumption of energy probably via melatonin receptors in adipose tissue. Itsaction at molecular level captured the attention of researchers of new drugs for obesity and metabolicsyndrome (7)(8).
References: 1. V Srinivasan1, SR Pandi-Perumal2, DP Cardinali3, B Poeggeler4 and R Hardeland; Melatonin in Alzheimers disease and other neurodegenerative disorders; Behavioral and Brain Functions 2006, 2:15 doi:10.1186/1744-9081-2-15 2. Nduhirabandi F, du Toit EF, LochnerA ; Melatonin and the metabolic syndrome: a tool for effective therapy in obesity-associated abnormalities?; ActaPhysiol (Oxf). 2012 Jun;205(2):209- 23. doi: 10.1111/j.1748-1716.2012.02410.x. Epub 2012 Feb 3. 3. RüdigerHardeland ; Melatonin Metabolism in the Central Nervous System ; CurrNeuropharmacol. 2010 September; 8(3): 168–181. doi: 10.2174/157015910792246244 PMCID: PMC3001211 4. VenkataramanujamSrinivasana, e, Edward C Lauterbachb, AsmaHayatiAhmedc, AtulPrasadd; Alzheimers Disease: Focus on the Neuroprotective Role of Melatonin; Journal of Neurology Research, ISSN 1923-2845 print, 1923-2853 online 5. Laura Perrone, PierluigiMarzuillo, Anna Grandone and Emanuele M del Giudice* ; Chromosome 16p11.2 deletions: another piece in the genetic puzzle of childhood obesity; Italian Journal of Pediatrics 2010, 36:43 doi:10.1186/1824-7288-36-43 6. Sumit Bhattacharyya, Jian’an Luan, Benjamin Challis et al ; Sequence Variants In The MelatoninRelated Receptor (GPR50) Gene Associated With Circulating Triglyceride and HDL Levels. From the University of Cambridge, 1 Departments of Medicine, 2 Clinical Biochemistry, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 2QQ, UK. Downloaded from www.jlr.org by guest, on November 10, 2012 7. Murray A Raskind, Brianna L Burke, Norman J Crites, Andre M Tapp and Dennis D Rasmussen; Olanzapine-Induced Weight Gain and Increased Visceral Adiposity is Blocked by Melatonin Replacement Therapy in Rats; Neuropsychopharmacology (2007) 32, 284–288. doi:10.1038/sj.npp.1301093; published online 10 May 2006 8. Pohanka M (2012) Would be Melatonin Suitable for Obesity Treatment? J ObesWt Loss Ther 2:e105. doi:10.4172/2165-7904.1000e105 ADONIS SFERA, MD