AIMS/HYPOTHESIS: Thiazolidinediones, a new class of insulin sensitizers, up-regulate the expression of uncoupling protein 2 in rodent adipocytes. It is not known, however, whether thiazolidinediones influence uncoupling protein 2 expression in human adipocytes. We therefore investigated the effect of these drugs on uncoupling protein 2 expression in the recently immortalized human PAZ6 adipocyte cell line. METHODS: Immortalized human PAZ6 preadipocytes were differentiated into adipocytes in the presence or absence of thiazolidinediones. The effect of the drugs on uncoupling protein 2 expression and adipocyte differentiation was measured by reverse transcription-polymerase chain reaction of mRNA of uncoupling protein 2 and of five adipocyte differentiation markers. RESULTS: When cells were differentiated 15 days in the presence of thiazolidinediones, uncoupling protein 2 expression was 2.1-fold higher than in the absence of the drugs. The expression of five adipocyte differentiation markers was, however, also increased by thiazolidinediones. Short-term incubation for 4 and 24 h with thiazolidinediones increased uncoupling protein 2 expression 1.35-fold and 2.3-fold, respectively. The expression of adipocyte markers studied in parallel was also augmented. CONCLUSION/ INTERPRETATION: Thiazolidinediones rapidly increase the expression of uncoupling protein 2 in human PAZ6 adipocytes but the increase of uncoupling protein 2 expression is always associated with an augmentation of the expression of all adipocyte markers studied in parallel. This indicates that the effect of thiazolidinediones on uncoupling protein 2 mRNA reflects a general increase in adipocyte differentiation rather than a specific augmentation of uncoupling protein 2 gene expression.
AIMS/HYPOTHESIS: Thiazolidinediones, a new class of insulin sensitizers, up-regulate the expression of uncoupling protein 2 in rodent adipocytes. It is not known, however, whether thiazolidinediones influence uncoupling protein 2 expression in human adipocytes. We therefore investigated the effect of these drugs on uncoupling protein 2 expression in the recently immortalized human PAZ6 adipocyte cell line. METHODS: Immortalized human PAZ6 preadipocytes were differentiated into adipocytes in the presence or absence of thiazolidinediones. The effect of the drugs on uncoupling protein 2 expression and adipocyte differentiation was measured by reverse transcription-polymerase chain reaction of mRNA of uncoupling protein 2 and of five adipocyte differentiation markers. RESULTS: When cells were differentiated 15 days in the presence of thiazolidinediones, uncoupling protein 2 expression was 2.1-fold higher than in the absence of the drugs. The expression of five adipocyte differentiation markers was, however, also increased by thiazolidinediones. Short-term incubation for 4 and 24 h with thiazolidinediones increased uncoupling protein 2 expression 1.35-fold and 2.3-fold, respectively. The expression of adipocyte markers studied in parallel was also augmented. CONCLUSION/ INTERPRETATION:Thiazolidinediones rapidly increase the expression of uncoupling protein 2 in human PAZ6 adipocytes but the increase of uncoupling protein 2 expression is always associated with an augmentation of the expression of all adipocyte markers studied in parallel. This indicates that the effect of thiazolidinediones on uncoupling protein 2 mRNA reflects a general increase in adipocyte differentiation rather than a specific augmentation of uncoupling protein 2 gene expression.
Authors: Andrew W Norris; Michael F Hirshman; Jianrong Yao; Niels Jessen; Nicolas Musi; Lihong Chen; William I Sivitz; Laurie J Goodyear; C Ronald Kahn Journal: Endocrinology Date: 2008-07-24 Impact factor: 4.736