OBJECTIVE: Adipocytes secrete a number of molecules such as tumor necrosis factor-alpha, leptin and free fatty acids that can influence the ability of the body to metabolize glucose. Recently, a novel 12.5 kDa cysteine-rich protein, termed resistin, was shown to be secreted by adipocytes. Resistin expression was markedly induced during the conversion of 3T3-L1 cells to mature adipocytes. Expression of resistin has been studied in human, mouse and rat; however, sequence information about an alternative splicing variant (ASV) of resistin mRNA has not been reported. In the present study, we investigated the occurrence of a novel ASV of the resistin gene in human normal tissues. DESIGN AND METHODS: We identified a novel ASV of resistin mRNA in human lung tissue by RT-PCR analysis in human lung tissue. We then investigated a novel ASV of resistin mRNA by real-time PCR analysis in 26 different types of normal human tissues. RESULTS AND CONCLUSIONS: We identified a novel deletion variant of the resistin transcript in the normal human tissues. The deleted transcript of resistin was characterized by an in-frame deletion of 78 bp, corresponding to the complete loss of exon 2 (resistin delta2 ASV). Thus, resistin delta2 ASV causes protein truncation. Our results provide the basis for more detailed studies on the regulation of resistin activity, and should assist in the development of clinical trials with resistin for the central regulation of adipogenesis and adipocyte metabolism.
OBJECTIVE: Adipocytes secrete a number of molecules such as tumor necrosis factor-alpha, leptin and free fatty acids that can influence the ability of the body to metabolize glucose. Recently, a novel 12.5 kDa cysteine-rich protein, termed resistin, was shown to be secreted by adipocytes. Resistin expression was markedly induced during the conversion of 3T3-L1 cells to mature adipocytes. Expression of resistin has been studied in human, mouse and rat; however, sequence information about an alternative splicing variant (ASV) of resistin mRNA has not been reported. In the present study, we investigated the occurrence of a novel ASV of the resistin gene in human normal tissues. DESIGN AND METHODS: We identified a novel ASV of resistin mRNA in human lung tissue by RT-PCR analysis in human lung tissue. We then investigated a novel ASV of resistin mRNA by real-time PCR analysis in 26 different types of normal human tissues. RESULTS AND CONCLUSIONS: We identified a novel deletion variant of the resistin transcript in the normal human tissues. The deleted transcript of resistin was characterized by an in-frame deletion of 78 bp, corresponding to the complete loss of exon 2 (resistin delta2 ASV). Thus, resistin delta2 ASV causes protein truncation. Our results provide the basis for more detailed studies on the regulation of resistin activity, and should assist in the development of clinical trials with resistin for the central regulation of adipogenesis and adipocyte metabolism.
Authors: Daniel J Angelini; Qingning Su; Kazuyo Yamaji-Kegan; Chunling Fan; John T Skinner; Hunter C Champion; Michael T Crow; Roger A Johns Journal: Am J Physiol Lung Cell Mol Physiol Date: 2009-01-09 Impact factor: 5.464