Downregulation of hepatic acyl-CoA:diglycerol acyltransferase in chronic renal failure.
Downregulation of hepatic acyl-CoA:diglycerol acyltransferase in chronic renal failure.
复制标题
慢性肾功能衰竭中肝酰基辅酶A:二甘油酰基转移酶的下调。
DOI:
10.1152/ajprenal.00358.2003
复制
发表时间:
2004
期刊:
影响因子:
--
通讯作者:
K. Liang
中科院分区:
文献类型:
--
作者:
Nosratola D. Vaziri;C. Kim;B. Dang;C. Zhan;K. Liang
Chronic renal failure (CRF) is associated with hypertriglyceridemia and elevated plasma VLDL and IDL concentrations. These events can be due to either increased production or depressed catabolism of triglyceride-rich lipoproteins. Several studies have documented downregulation of lipoprotein lipase, hepatic triglyceride lipase, and the VLDL receptor, leading to depressed clearance and elevated plasma concentration of triglyceride-rich lipoproteins and their remnants in CRF. However, the effect of CRF on the triglyceride biosynthetic pathway has not been explored. Diglycerol acyltransferase (DGAT) is a microsomal enzyme that joins acyl-CoA to 1,2 diacylglycerol and, as such, constitutes the final step in triglyceride biosynthesis. Two distinct forms of DGAT (DGAT-1 and -2) have thus far been identified. The present study was undertaken to examine the effect of CRF on DGAT gene expression and activity in the liver, which is the source of endogenous triglycerides in the circulation. Male Sprague-Dawley rats were studied 8 wk after 5/6 nephrectomy (CRF) or sham operation. DGAT-1 and DGAT-2 mRNA abundance and DGAT activity were quantified. The CRF group showed reduced creatinine clearance, elevated plasma triglycerides, and VLDL concentrations. This was accompanied by significant reductions in hepatic DGAT-2 mRNA abundance (P < 0.01) and total DGAT activity (P < 0.1), pointing to diminished hepatic triglyceride production capacity in CRF animals. In conclusion, CRF results in significant downregulation of hepatic DGAT gene expression and activity. Given the critical role of DGAT in triglyceride biosynthesis, the present study points to diminished, not increased, hepatic triglyceride synthetic capacity in CRF rats.
影响因子:
--
作者:
Coleman,RA
通讯作者:
Coleman,RA
DOI:
10.1152/ajprenal.2001.280.5.f823
发表时间:
2001
期刊:
American journal of physiology. Renal physiology
影响因子:
--
作者:
Vaziri,ND;Liang,K;Parks,JS
通讯作者:
Parks,JS
DOI:
10.1073/pnas.95.22.13018
发表时间:
1998-10-27
影响因子:
11.1
作者:
Cases, S;Smith, SJ;Farese, RV
通讯作者:
Farese, RV