Biochemical pharmacology
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Biochemical pharmacology · Sep 2018
ReviewNew approaches targeting brown adipose tissue transplantation as a therapy in obesity.
Brown adipose tissue (BAT) is raising high expectations as a potential target in the fight against metabolic disorders such as obesity and type 2 diabetes. BAT utilizes fuels such as fatty acids to maintain body temperature by uncoupling mitochondrial electron transport to produce heat instead of ATP. This process is called thermogenesis. ⋯ Furthermore, recent studies have tested a therapeutic approach to directly increase BAT mass by the implantation of either adipocytes or fat tissue. This approach might have an important future in regenerative medicine and in the fight against metabolic disorders. Here, we review the emerging field of BAT transplantation including the various sources of mesenchymal stem cell isolation in rodents and humans and the described metabolic outcomes of adipocyte cell transplantation and BAT transplantation in obesity.
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Biochemical pharmacology · Sep 2018
In vitro approach to elucidate the relevance of carboxylesterase 2 and N-acetyltransferase 2 to flupirtine-induced liver injury.
The use of flupirtine, an analgesic, has been restricted in European countries because it causes liver injury in rare cases. Flupirtine is primarily metabolized to D-13223, an acetylamino form. In the process of D-13223 formation, it has been hypothesized that a reactive metabolite is formed which may be involved in flupirtine hepatotoxicity. ⋯ The formation of the NAC conjugate in liver S9 samples from NAT2 slow acetylators was significantly higher than that from NAT2 rapid/intermediate acetylators, indicating that NAT2 could function as a detoxification enzyme for flupirtine. CES2-overexpressing HepG2 cells showed remarkable lactate dehydrogenase leakage under flupirtine treatment, while no cytotoxicity was observed in control cells, suggesting that the reactive metabolite formed by CES2-mediated hydrolysis of flupirtine would be a trigger of hepatotoxicity. NAT2 slow acetylators with high CES2 activity could be highly susceptible to flupirtine-induced liver injury.