Functional analysis of a novel metabolic syndrome related gene

点击翻译按钮获取中文摘要

SNPs in the obesity-related gene 3, that is myotubularin-related protein 9 (MTMR9) gene, was associated with obesity and hypertension. The mRNA with risk alleles of SNPs existed in 37UTR was less stable that that without risk alleles, suggesting that the mRNA levels of MTMR9 would be reduced in obese patients. Both the transcript and protein of MTMR9 were detected in the rodent lateral hypothalamic area as well as in the arcuate nucleus, an the protein co-existed with orexin, meanin concentrating hormone, neuropeptide Y (NPY) and proopiomelanocrotin. MTMR9 is belongs to myotularin family that possesses protein-tyrosine phosphatase activities. MTMR9, however, lacks phosphatase activity. MTMR9 interacts active phosphatase MTMR6 and MTMR7. MTMR9 and MTMR7 proteins were expressed in the same cell, suggesting that MTMR9 could act in the haypothalamic region together with MTMR7. The levels of MTMR9 transcript in the murine hypothalamic region increased after fasting and were decreased by a high-fat-diet in parallel with NPY and agouti-relate protein (AGRP). Thus, MTMR9 would be involved in appetite regulation. The level of MTMR9 transcript did not differ between ob/ob or db/db and control mice. These data suggested that MTMR9 may be the downstream of lepin signal. We identified the gentic variations in MTMR9 tha may influence the risk of obesity and hypertension in a large-scale case-control association study. We have demonstrated that the possibility that MTMR9 could involved in appetite regulation.