- 作者: Masashi Niimi; Lian Tao; Shi-Hua Lin; Jun Yin; Xiaoyun Wu; Hiroyuki Fukui; Junichi Kambayashi; Jianping Ye; Bing Sun
- 作者服務機構: Otsuka Maryland Medicinal Laboratories, Inc, Rockville, Maryland, USA,
- 中文摘要: --
- 英文摘要:
Background: Adipogenesis is a complex process that involves many genes/proteins at different
stages of differentiation. In order to identify genes critical for adipogeneis, we took a novel
approach based on phenotype change of individual cell, to search for genes with regulatory roles
in adipogenesis genome-wide in 3T3-L1 cells.
Methods: Lentivirus-based inducible random homologous knockdown was used for the screening
of functional gene that altered lipid formation in the adipocyte during differentiation.
Results: In the present study, we reported the identification of an alternatively spliced
mitochondrial oxodicarboxylate carrier (ODC), so named ODC-AS. ODC-AS is different from
ODC by replacing 22 amino acids with 29 amino acids at the N-terminal. ODC was widely
expressed in most tissues in mouse as determined by multi-tissue cDNA panel polymerase chain
reaction. However, ODC-AS was only detected in adipose tissue and in iris and sclera-choroid
complex of the eye. The expression of ODC-AS in 3T3-L1 was detected after the induction of
differentiation, and reached a peak at day 4 and then reduced thereafter, whereas no ODC
transcript detected in the cells neither before nor after differentiation. Knocking down of ODCAS
expression by RNA interference led to significant reduction in lipid accumulation as determined
by triglyceride measurement and Nile Red staining, as well as adipogenic marker CEBPα, PPARγ,
aP2 and CD36. Although both ODC and ODC-AS are expressed in white and brown adipose
tissues, only the expression of ODC-AS was down-regulated in brown adipose tissue by cold
exposure.
Conclusion: These results implicate that ODC-AS may promote lipid accumulation during
adipocyte differentiation and play an important role in the regulation of lipid metabolism in adipose
tissues. - 中文關鍵字: --
- 英文關鍵字: --