Introduction: What they say
A study from the Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, Florida 33458, USA shows that “Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists.” This research paper was published, in the 29 March 2012 issue of the journal “Nature” [One of the best research journals in Science with an I.F of 43 plus], by Prof.Burris TP, Solt LA and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Molecular therapy for body weight control, energy homeostasis and TIIDM: Melatonin, a hormone that regulates sleep and wakefulness, increases REV-ERB and its down stream target genes, inhibits lipid accumulation, improves dyslipidemia and insulin sensitivity, increases energy utilization, promotes weight loss and protects from diet-induced obesity and TIIDM via up regulation of its target gene
From significance of the study to public health relevance:
Given that: (1) more than half a billion adults are obese worldwide ; (2) obesity is more prevalent in western countries than in asian countries; (3) obesity results in deregulated blood pressure, cholesterol, triglycerides and insulin sensitivity; and the risks of coronary heart disease, ischemic stroke and TII diabetes mellitus(TIIDM) increase ; (4) more than 422 million people worldwide are affected by Diabetes mellitus (DM); (5) Diabetes is going to be one of the top 10 causes of death by 2030; (6) the life-long painful injection/drug treatment is required to treat DM; and (7) the global economic cost spent for diabetes treatment in 2014 was little more than 600 billion US dollars, there is an urgent need to find: (i) a way to induce regeneration of adult ß-cells that were lost in DM; (ii) a cheaper alternative to the existing expensive weight-loss drugs; (iii) a side-effect-free natural product-based drug; and (iv) a way to cure, not just treat, obesity-associated diseases, including diabetes.
What is known?
Prof.Burris’s research team has recently shown that administration of REV-ERB ligands:(1) regulates circadian behaviour and the circadian pattern of core clock gene;(2) alters the circadian pattern of expression of metabolic genes in liver, skeletal muscle and adipose tissue; (3) increases energy expenditure; (4) inhibits lipid accumulation; (4) decreases obesity; (5) improves dyslipidemia; and (6) reduces hyperglycaemia, suggesting that increasing the expression of REV-ERB may promote weight loss, augment insulin sensitivity, improve dyslipidemia and alleviate Obesity-associated TIIDM.
From research findings to Therapeutic opportunity:
This study suggests provides mechanistic insights into how Fluoxetine may promote weight loss and attenuate obesity-associated TIIDM. Melatonin, by increasing the expression of its target gene, it may increase the expression of REV-ERB. Thereby, it may: (1) normalize circadian pattern of metabolic genes; (2) augment energy expenditure; (3) inhibit lipid accumulation; (4) promote weight loss; (5) ameliorate dyslipidemia; and (6) inhibit hyperglycemia (Fig.1). Thus, pharmacological formulations encompassing “Melatonin or its analogues/activators, either alone or in combination with other drugs” may be used:(i) as a weight-loss medication; (ii) to treat Obesity-associated TIIDM; (iii) to treat sleep disorders (Fig.2).
Details of the research findings:
Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.
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Undisclosed mechanistic information: How does Melatonin increase the expression of REV-ERB to promote Weight loss?
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Citation: Boominathan, L., Molecular therapy for body weight control, energy homeostasis and TIIDM: Melatonin, a hormone that regulates sleep and wakefulness, increases REV-ERB and its down stream target genes, inhibits lipid accumulation, improves dyslipidemia and insulin sensitivity, increases energy utilization, promotes weight loss and protects from diet-induced obesity and TIIDM via up regulation of its target gene, 17/January/2018, 10.10 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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