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Anabolic Steroids
looking for scientific info on DNP
- Thread starter iron
- Start date
I must admit I'm kinda interested in a DNP clinical trial. All I need is an orphan drug application and a couple of million dollars to perform inpatient Phase I/II/III trials. Phase I would go pretty quickly (assuming my IRB would approve it) since 600mg would likely be the max dose. Phase II/III would likely be limited by recruitment issues.Bob Smith said:
I'm planning to sample some DNP myself starting next week.
einstein1905
New Member
FASEB J. 2000 Sep;14(12):1793-800. Related Articles, Links
Decreased fatty acid synthesis due to mitochondrial uncoupling in adipose tissue.
Rossmeisl M, Syrovy I, Baumruk F, Flachs P, Janovska P, Kopecky J.
Department of Adipose Tissue Biology, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Synthesis of fatty acid (FA) in adipose tissue requires cooperation of mitochondrial and cytoplasmic enzymes. Mitochondria are required for the production of ATP and they also support the formation of acetyl-CoA and NADPH in cytoplasm. Since cellular levels of all these metabolites depend on the efficiency of mitochondrial energy conversion, mitochondrial proton leak via uncoupling proteins (UCPs) could modulate FA synthesis. In 3T3-L1 adipocytes, 2,4-dinitrophenol depressed the synthesis of FA 4-fold while increasing FA oxidation 1. 5-fold and the production of lactate 14-fold. Inhibition of FA synthesis in 3T3-L1 adipocytes was proportional to the decrease in mitochondrial membrane potential. FA synthesis from D-[U-(14)C] glucose was reduced up to fourfold by ectopic UCP1 in the white fat of transgenic aP2-Ucp1 mice, reflecting the magnitude of UCP1 expression in different fat depots and the reduction of adiposity. Transcript levels for lipogenic enzymes were lower in the white fat of the transgenic mice than in the control animals. Our results show that uncoupling of oxidative phosphorylation depresses FA synthesis in white fat. Reduction of adiposity via mitochondrial uncoupling in white fat not only reflects increased energy expenditure, but also decreased in situ lipogenesis.
J Nutr Biochem. 2003 Apr;14(4):219-26. Related Articles, Links
Effects of mitochondrial uncoupling on adipocyte intracellular Ca(2+) and lipid metabolism.
Sun X, Zemel MB.
University of Tennessee, Knoxville, TN 37996, USA.
Previous data from this laboratory demonstrate that increased intracellular Ca(2+) ([Ca(2+)]i) coordinately regulates human and murine adipocyte lipid metabolism by stimulating lipogenesis and inhibiting lipolysis. However, recent data demonstrate metabolic uncoupling increases [Ca(2+)]i but inhibits lipogenesis by suppressing fatty acid synthase (FAS) activity. Accordingly, we have evaluated the interaction between mitochondrial uncoupling, adipocyte [Ca(2+)]i, and adipocyte lipid metabolism. Pretreatment of 3T3-L1 cells with mitochondrial uncouplers (DNP or FCCP) amplified the [Ca(2+)]i response to depolarization with KCl by 2-4 fold (p <0.001), while this increase was prevented by [Ca(2+)]i channel antagonism with lanthanum. Mitochondrial uncouplers caused rapid (within 4hr) dose-dependent inhibition of FAS activity (p <0.001), while lanthanum caused a further additive inhibition. The suppression of FAS activity induced by uncoupling was reversed by addition of ATP. Mitochondrial uncouplers increased FAS expression significantly while [Ca(2+)]i antagonism with lanthanum decreased FAS expression (P <0.001). In contrast, mitochondrial uncouplers independently inhibited basal and isoproterenol-stimulated lipolysis (20-40%, p <0.001), while this inhibition was fully reversed by lanthanum. Thus, mitochondrial uncoupling exerted short-term regulatory effects on adipocyte [Ca(2+)]i and lipogenic and lipolytic systems, serving to suppress lipolysis via a Ca(2+) -dependent mechanism and FAS activity via a Ca(2+)-independent mechanism.
Decreased fatty acid synthesis due to mitochondrial uncoupling in adipose tissue.
Rossmeisl M, Syrovy I, Baumruk F, Flachs P, Janovska P, Kopecky J.
Department of Adipose Tissue Biology, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Synthesis of fatty acid (FA) in adipose tissue requires cooperation of mitochondrial and cytoplasmic enzymes. Mitochondria are required for the production of ATP and they also support the formation of acetyl-CoA and NADPH in cytoplasm. Since cellular levels of all these metabolites depend on the efficiency of mitochondrial energy conversion, mitochondrial proton leak via uncoupling proteins (UCPs) could modulate FA synthesis. In 3T3-L1 adipocytes, 2,4-dinitrophenol depressed the synthesis of FA 4-fold while increasing FA oxidation 1. 5-fold and the production of lactate 14-fold. Inhibition of FA synthesis in 3T3-L1 adipocytes was proportional to the decrease in mitochondrial membrane potential. FA synthesis from D-[U-(14)C] glucose was reduced up to fourfold by ectopic UCP1 in the white fat of transgenic aP2-Ucp1 mice, reflecting the magnitude of UCP1 expression in different fat depots and the reduction of adiposity. Transcript levels for lipogenic enzymes were lower in the white fat of the transgenic mice than in the control animals. Our results show that uncoupling of oxidative phosphorylation depresses FA synthesis in white fat. Reduction of adiposity via mitochondrial uncoupling in white fat not only reflects increased energy expenditure, but also decreased in situ lipogenesis.
J Nutr Biochem. 2003 Apr;14(4):219-26. Related Articles, Links
Effects of mitochondrial uncoupling on adipocyte intracellular Ca(2+) and lipid metabolism.
Sun X, Zemel MB.
University of Tennessee, Knoxville, TN 37996, USA.
Previous data from this laboratory demonstrate that increased intracellular Ca(2+) ([Ca(2+)]i) coordinately regulates human and murine adipocyte lipid metabolism by stimulating lipogenesis and inhibiting lipolysis. However, recent data demonstrate metabolic uncoupling increases [Ca(2+)]i but inhibits lipogenesis by suppressing fatty acid synthase (FAS) activity. Accordingly, we have evaluated the interaction between mitochondrial uncoupling, adipocyte [Ca(2+)]i, and adipocyte lipid metabolism. Pretreatment of 3T3-L1 cells with mitochondrial uncouplers (DNP or FCCP) amplified the [Ca(2+)]i response to depolarization with KCl by 2-4 fold (p <0.001), while this increase was prevented by [Ca(2+)]i channel antagonism with lanthanum. Mitochondrial uncouplers caused rapid (within 4hr) dose-dependent inhibition of FAS activity (p <0.001), while lanthanum caused a further additive inhibition. The suppression of FAS activity induced by uncoupling was reversed by addition of ATP. Mitochondrial uncouplers increased FAS expression significantly while [Ca(2+)]i antagonism with lanthanum decreased FAS expression (P <0.001). In contrast, mitochondrial uncouplers independently inhibited basal and isoproterenol-stimulated lipolysis (20-40%, p <0.001), while this inhibition was fully reversed by lanthanum. Thus, mitochondrial uncoupling exerted short-term regulatory effects on adipocyte [Ca(2+)]i and lipogenic and lipolytic systems, serving to suppress lipolysis via a Ca(2+) -dependent mechanism and FAS activity via a Ca(2+)-independent mechanism.
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