Session: OR51-Obesity: From Genes to Populations
Room 303 (Moscone Center)
Methods: By using lentiviral-mediated expression of shRNA, we generated FTO deficient SGBS pre- and adipocytes. Successful knockdown and expression of marker genes involved in adipogenic differentiation and glucose and lipid metabolism were monitored by qPCR. Relative mitochondrial content was determined by measurement of citrate synthase activity. Cellular oxygen consumption rates were analyzed by cell respirometry.
Results: In human SGBS preadipocytes and adipocytes we reached a transduction efficiency of >90%. This led to an inhibition of FTO mRNA expression by 73% and to a total repression of FTO protein expression. FTO deficiency did not affect differentiation into mature adipocytes. Interestingly, expression of uncoupling protein 1 (UCP-1) was approximately 4-fold increased in mitochondria of FTO deficient adipocytes compared to preadipocytes. This led to an increased basal as well as uncoupled mitochondrial respiration in FTO deficient adipocytes. In both gonadal and inguinal adipose tissues of FTO deficient mice, expression of brown adipocyte markers and appearance of multivacuolar adipocytes were detected.
Conclusions: We conclude that FTO deficiency leads to the induction of a brown adipocyte phenotype, thereby enhancing energy expenditure. Further understanding of the signaling pathways connecting FTO with UCP-1 expression might lead to new options for obesity treatment.
Nothing to Disclose: DT, PF, TF, MK, JF, UR, MW
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