2,4-Dinitrophenol (DNP) is a mitochondrial uncoupler that inhibits ATP production in cells. Instead of producing ATP, the energy is lost as heat, leading to rapid weight loss. From 1933 to 1938, it was marketed as a weight loss drug.
However, DNP causes fatal hyperthermia due to the heat produced during mitochondrial uncoupling. Although DNP has been discontinued in 1938, some daredevils use the drug to control weight secretly. For example, Leeds University student Sarah Houston died from taking DNP in 2012.
Scientists at Yale University developed a controlled-release DNP called CRMP to improve its safety margin, according to a report published in the journal Science.
In contrast to DNP, which caused a dose-dependent increase in body temperature at doses above 25 mg/kg, CRMP had a negligible effect on temperature at doses less than 100 mg/kg. The LD50 dose of CRMP was more than 10-fold higher than that of DNP (~400 vs 40 mg/kg).
Rats treated with 1 mg/kg of CRMP exhibited significant reductions in fasting plasma glucose, fatty acid, triglyceride and plasma insulin. In a rat model of NASH, CRMP reduced liver triglyceride by 90% and normalized plasma ALT and AST levels.
NASH has become a buzzword since Intercept Pharmaceuticals (NASDAQ: ICPT) shares rocketed in January 2014. I hope this encouraging research would be translated to humans.
 Science. 2015, doi: 10.1126/science.aaa0672.
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