The effects of chronic AMPK activation on hepatic triglyceride accumulation and glycerol 3-phosphate acyltransferase activity with high fat feeding.
The effects of chronic AMPK activation on hepatic triglyceride accumulation and glycerol 3-phosphate acyltransferase activity with high fat feeding.
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DOI：
10.1186/1758-5996-5-29
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发表时间：
2013
影响因子：
4.8
通讯作者：
Hancock CR
中科院分区：
文献类型：
--
作者：
Henriksen BS;Curtis ME;Fillmore N;Cardon BR;Thomson DM;Hancock CR
高脂饮食会增加肝脏脂肪堆积，并与肝脏胰岛素抵抗有关。AMPK被认为通过急性抑制甘油-3-磷酸酰基转移酶(GPAT)活性和通过固醇调节元件结合蛋白-1c(SREBP-1c)进行转录调节来抑制脂质合成。这项研究的目的是确定长期激活AMPK是否能阻止高脂饮食大鼠GPAT1活性的增加。对照组(C)或高脂(HF)饲料(60%脂肪)喂养6周，并注射生理盐水或每日0.5 mg/g体重的氨基咪唑甲酰胺核苷酸(AICAR)。长期注射AICAR激活AMPK后，C组和HF组大鼠肝脏甘油三酯蓄积均显著减少(C组，5.5±0.7；C+AICAR组，2.7±0.3；HF组，21.8±3.3；HF+AICAR组，8.0±1.8 mg/g肝)。摄食HF可增加GPAT和GPAT1的总活性，但不受慢性AMPK激活的影响(GPAT1活性vs.C，C+AICAR，92±19%；HF，186±43%；HF+AICAR，234±62%)。氧化能力的指标，包括柠檬酸合成酶活性和细胞色素c丰度，不受慢性AICAR治疗的影响。有趣的是，饲喂HF导致长链酰辅酶A脱氢酶(LCAD)显著增加(比C增加66%)，这是脂肪酸氧化能力的标志。这些结果表明，慢性AMPK激活限制了肝脏甘油三酯的积累，而不是与总GPAT1活性的降低无关。
High fat feeding increases hepatic fat accumulation and is associated with hepatic insulin resistance. AMP Activated Protein Kinase (AMPK) is thought to inhibit lipid synthesis by the acute inhibition of glycerol-3-phosphate acyltransferase (GPAT) activity and transcriptional regulation via sterol regulatory element binding protein-1c (SREBP-1c). The purpose of this study was to determine if chronic activation of AMPK prevented an increase in GPAT1 activity in rats fed a high fat diet. Rats were fed a control (C), or a high fat (HF) diet (60% fat) for 6 weeks and injected with saline or a daily aminoimidazole carboxamide ribnucleotide (AICAR) dose of 0.5 mg/g body weight. Chronic AMPK activation by AICAR injections resulted in a significant reduction in hepatic triglyceride accumulation in both the C and HF fed animals (C, 5.5±0.7; C+AICAR, 2.7 ±0.3; HF, 21.8±3.3; and HF+AICAR, 8.0±1.8 mg/g liver). HF feeding caused an increase in total GPAT and GPAT1 activity, which was not affected by chronic AMPK activation (GPAT1 activity vs. C, C+AICAR, 92±19%; HF, 186±43%; HF+AICAR, 234±62%). Markers of oxidative capacity, including citrate synthase activity and cytochrome c abundance, were not affected by chronic AICAR treatment. Interestingly, HF feeding caused a significant increase in long chain acyl-CoA dehydrogenase or LCAD (up 66% from C), a marker of fatty acid oxidation capacity. These results suggest that chronic AMPK activation limits hepatic triglyceride accumulation independent of a reduction in total GPAT1 activity.
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影响因子：
3.3
作者：
Fillmore, Natasha;Jacobs, Daniel L.;Hancock, Chad R.
通讯作者：
Hancock, Chad R.
影响因子：
13.5
作者：
Hwahng, Seong Hwan;Ki, Sung Hwan;Kim, Sang Geon
通讯作者：
Kim, Sang Geon
DOI：
10.1152/ajpendo.00144.2005
发表时间：
2005-11-01
影响因子：
5.1
作者：
Assifi, MM;Suchankova, G;Ruderman, NB
通讯作者：
Ruderman, NB
影响因子：
4.4
作者：
Kim, Hyun-Jin;Kim, Jin Hee;Yoon, Suk Hoo
通讯作者：
Yoon, Suk Hoo
影响因子：
4.1
作者：
BRADY, LJ;BRADY, PS;HOPPEL, CL
通讯作者：
HOPPEL, CL