Reducción de la eficiencia energética en mitocondrias hepáticas mediante transferencia génica de ucpi

Resumen

TITULO: Reducción DE LA eficiencia energética EN mitocondrias hepáticas mediante Transferencia génica DE UCPl RESUMEN: Most current obesity treatments are based on increasing energy expenditure diminishing energy intake. in this sense, the stimulation of energy reléase heat, known as adaptive thermogenesis, would influence the whole energy expenditure. The Uncoupling Protein 1 (UCPl) or thermogenin , an internal mitochondrial membrane protein uniquely expressed in brown adipose tissue, the main molecule responsible for the adaptive thermogenesis. This protein dissipates the protón gradient generated in the mitocondrial respiration producing heat, diminishing mitochondria energy efficiency. Gene transfer would allow expressing UCP1 in other tissues that could be suitable for obesity treatment in humans. The aim of this study was to ectopically express UCPl by gene transfer in "liver mitochondria ("in vitro" and "in vivo) in order to affect energy utilization. ¿In vitro", the effect of ectopic protein expression on energy metabolism of HepG2 cells showed that cells expressing UCPl had decreased ATP production. "in vivo", mitochondria from liver of ectopic UCPl transferred mice showed a decrease on ATP production, lasted more time in the membrane potential state 3, and consumed more molecular oxygen to produce the same amount of ATP than those of control group. Furthermore, the UCPl transferred group tended to have a smaller respiratory control ratio than the control group. In summary, gene transfer in liver cells to ectopically express the UCPl protein could be an approach to manage metabolic disorders related to energy efficiency and expenditure, such as obesity, by dissipating energy excess.