Natural product-based exercise mementics therapy for Metabolic disease: A therapeutic mix encompassing 15-deoxy-(Delta12,14)-prostaglandin J2 (15d-PGJ2) increases PPARδ  and Foxo1 levels, inhibits glucose catabolism, preserves glucose levels, stimulates FA catabolism, delays the onset of hypoglycemia and boosts endurance exercise via down regulation of its target gene, 09/October/2017, 11.53 pm

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Introduction: What they say 

A study from Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA shows that “CRY1/2 Selectively Repress PPARδ and Limit Exercise Capacity.” This research paper was published, in the 2 May 2017 issue of the journal “Cell Metabolism” [One of the best research journals in Metabolism with an I.Fs of 30.357], by Prof.Lamia KA, Jordan and others.

Earlier, a study from the Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA shows that “PPARδ Promotes Running Endurance by Preserving Glucose.” This research paper was published, in the 2 May 2017 issue of the journal “Cell Metabolism” [One of the best research journals in Metabolism with an I.Fs of 30.357], by Prof.Ronald M. Evans, Weiwei Fan and others.


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that:  Natural product-based exercise mementics therapy for Metabolic disease: A therapeutic mix encompassing 15-deoxy-(Delta12,14)-prostaglandin J2 (15d-PGJ2) increases PPARδ  and Foxo1 levels, inhibits glucose catabolism, preserves glucose levels, stimulates FA catabolism, delays the onset of hypoglycemia and boosts endurance exercise via down regulation of its target gene


From the Significance of the study to Public health relevance:

Given that: (1) metabolic disease is the principal cause for a number of human diseases; (2) metabolic disease approximately affects 60% of population older than 50 years; (3) metabolic disease affects 30-32% of adult population worldwide; (4) metabolic disease is characterized by abdominal (central) obesity, increased blood pressure, large increase in fasting plasma glucose, high serum triglycerides, low high-density lipoprotein (HDL) levels and high low-density lipoprotein (LDL) levels; (5) prolonged uncontrolled metabolic disease may result in atherosclerosis, diabetes, hypertension, cardiovascular disease etc., (6) the raise of death rate, due to metabolic disease, has increased considerably in the last few decades; (7) 13% of cardiovascular disease occur due to uncontrolled high blood pressure; (8) in India, in 2004, 14.6 lakhs deaths (14% of total deaths) were due to ischemic heart disease; (9) 85% of people over 80 years are susceptible to cardiovascular diseases; (10) the global economic cost spent in the treatment of metabolic disease is enormous; and (11) the death due to cardiovascular disease is higher in low-to-middle income countries compared to developed countries, there is an urgent need to find: (i) a cure to metabolic diseases leading to a number of health complications, as mentioned above; (ii) a way to induce exercise endurance and performance in older people and in athletic individuals; (iii) a cheaper alternative to the existing expensive drugs; and (iv) a side-effect-free Natural product-based drug that alleviates metabolic disease, and boosts exercise performance in older individuals.


What is known?

PPARδ has been shown to play a central role in exercise endurance. However, the details about the components that function downstream of PPARδ in promoting exercise endurance is far from clear.

Prof. Ronald M. Evans’s research team has recently shown that increased expression of PPARδ: (1) by exercise mimetics promotes endurance; (2) increases running time significantly; (3) decreases the expression of genes involved in glucose uptake, glycolysis, and mitochondrial pyruvate entry such as Hk2, Gck, and mitochondrial pyruvate carrier (Mcp1); (4) increases mitochondrial gatekeeper genes Cpt1b and Pdk4; (5) up regulates genes involved in FA transport, FA oxidation, lipogenesis, and gluconeogenesis; (6) increases FA catabolism, decreases glycolysis and preserves systemic glucose; and (7) promotes endurance.

More recently, Dr. Katja Lamia’s research team has shown that: (1) overexpression of circadian repressors CRY1 and CRY2 inhibits the expression of PPARδ; (2) knocking out Cry1 and Cry2 in muscles escalates the expression of PPARδ; (3) CRY1/2 decrease the expression a selected set of PPARδ target genes in muscles; (4) deletion of Cry1/2 in mice improves exercise performance; (5) CRY1/2 modulate the expression of a number of genes involved in exercise physiology, including CLOCK/BMAL1; and (6) CRY1/2 regulate energy storage and play a critical role in substrate selection for energy production, suggesting that inhibiting the expression of Cry1/2 may improve exercise performance.


From Research findings to Therapeutic opportunity:

This study suggests a natural product-based therapy to increase exercise endurance.

A therapeutic mix encompassing 15-deoxy-(Delta12,14)-prostaglandin J2 (15d-PGJ2), by increasing the expression of its target gene, it may decrease the expression of circadian repressors CRY1 and CRY2. Thereby, it may: (1) increase the expression of PPARδ and its down stream target genes; (2) augment the expression of Foxo1; (3) decrease the expression of genes involved in glucose uptake and transport metabolism such as Hk2, Gck, and Mcp1; (4) increase the expression of mitochondrial gatekeeper genes Cpt1b and Pdk4; (5) increase the expression of genes that govern FA transport, FA oxidation, lipogenesis, and gluconeogenesis; (6) promote endurance; and (7) augment exercise performance (fig 1).

 

Figure1. Mechanistic insights into how a therapeutic mix encompassing 5-deoxy-(Delta12,14)-prostaglandin J2 (15d-PGJ2) increases PPARδ levels, decreases glycolysis, preserves systemic glucose levels, promotes endurance and augments exercise performance.

 

Thus, pharmacological formulations encompassing 15-deoxy-(Delta12,14)-prostaglandin J2 (15d-PGJ2) or its analogues, either alone or in combination with other compounds that are used to boost exercise/athletic performance” can be used to augment endurance and exercise performance; and treat metabolic diseases.


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/

Amount: $ 500#

Undisclosed mechanistic information: How a therapeutic mix encompassing 15-deoxy-(Delta12,14)-prostaglandin J2 (15d-PGJ2) increases PPARδ & Foxo1 levels, decreases glycolysis, preserves systemic glucose levels, promotes endurance and exercise capacity.

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References:

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

Citation: Boominathan, L., Natural product-based exercise mementics therapy for Metabolic disease: A therapeutic mix encompassing 15-deoxy-(Delta12,14)-prostaglandin J2 (15d-PGJ2) increases PPARδ  and Foxo1 levels, inhibits glucose catabolism, preserves glucose levels, stimulates FA catabolism, delays the onset of hypoglycemia and boosts endurance exercise via down regulation of its target gene, 09/October/2017, 11.55 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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