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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: Mechanistic insights into how Ciliary neurotrophic factor (CNTF) aids in control of body weight, energy homeostasis and TIIDM:  CNTF 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:

Ciliary neurotrophic factor (CNTF) has not only been shown to function as a strong survival factor for neurons and oligodendrocytes, but also  promote substantial weight loss and reduce food intake. However, the mechanistic basis of this remains largely obscure. 

This study suggests, for the first time, that Ciliary neurotrophic factor (CNTF), by increasing the expression of its target gene, it may increase the expression of REV-ERB (Fig.1). 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 (Figs.1-2).

Thus, pharmacological formulations encompassing CNTF 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 (Figs.3-4).

Figure 1. Mechanistic insights into how Ciliary neurotrophic factor (CNTF) attenuates metabolic disease and obesity-associated TIIDM.  CNTF, by up regulating the expression of its target gene, it may increase REV-ERB. And thereby it may attenuate metabolic disease and obesity-associated TIIDM.

Figure 2.  Ciliary neurotrophic factor (CNTF) promotes weight loss and attenuates metabolic disease through induction of Rev-ERB.

Figure 3. While pharmacological intervention induce REV-ERalpha and attenuate obesity and metabolic disease,, CNTF functions as an anti-diabetic agent, by up regulating the expression of REV-ERalpha and other anti-diabetic genes, and down regulating the expression of TXNIP.  

Figure 4. CNTF promotes weight loss and attenuates metabolic disease through induction of circadian protein Rev-ERBalpha.


Details of the research findings:

Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Undisclosed mechanistic information: How does  CNTF increase the expression of REV-ERB?

Amount: $500#

# Research cooperation

For purchase and payment details, you may reach us at info@genomediscovery.org


References:

Web: http://genomediscovery.org or http://newbioideas.com

Citation: Boominathan, L.,  Mechanistic insights into how Ciliary neurotrophic factor (CNTF) aids in control of body weight, energy homeostasis and TIIDM:  CNTF 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, 20/June/2019, 10.50 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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