The effects of chronic AMPK activation on hepatic triglyceride accumulation and glycerol 3-phosphate acyltransferase activity with high fat feeding

Diabetology & Metabolic Syndrome

Chad R Hancock¹  David M Thomson²  Brandon R Cardon¹  Natasha Fillmore²  Mary E Curtis¹  Bradley S Henriksen¹ 

[1] Department of Nutrition, Dietetics, and Food Science, Brigham Young University, Provo, UT 84602, USA;Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA

关键词: LCAD;    mTOR;    SREBP-1c;    GPAT1;    AMPK;   

Others  :  812738
DOI  :  10.1186/1758-5996-5-29

 received in 2012-11-21, accepted in 2013-05-18,  发布年份 2013

【 摘 要 】

Background

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).

Methods

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.

Results

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.

Conclusions

These results suggest that chronic AMPK activation limits hepatic triglyceride accumulation independent of a reduction in total GPAT1 activity.

【 授权许可】

   
2013 Henriksen et al.; licensee BioMed Central Ltd.

【 图 表 】

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