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Henriksen BS, Curtis ME, Fillmore N, et al. The effects of chronic AMPK activation on hepatic triglyceride accumulation and glycerol 3-phosphate acyltransferase activity with high fat feeding. Diabetol Metab Syndr. 2013;5:29doi: 10.1186/1758-5996-5-29.
Henriksen, B. S., Curtis, M. E., Fillmore, N., Cardon, B. R., Thomson, D. M., & Hancock, C. R. (2013). The effects of chronic AMPK activation on hepatic triglyceride accumulation and glycerol 3-phosphate acyltransferase activity with high fat feeding. Diabetology & metabolic syndrome, 529. https://doi.org/10.1186/1758-5996-5-29
Henriksen, Bradley S, et al. "The effects of chronic AMPK activation on hepatic triglyceride accumulation and glycerol 3-phosphate acyltransferase activity with high fat feeding." Diabetology & metabolic syndrome vol. 5 (2013): 29. doi: https://doi.org/10.1186/1758-5996-5-29
Henriksen BS, Curtis ME, Fillmore N, Cardon BR, Thomson DM, Hancock CR. The effects of chronic AMPK activation on hepatic triglyceride accumulation and glycerol 3-phosphate acyltransferase activity with high fat feeding. Diabetol Metab Syndr. 2013 May 31;5:29. doi: 10.1186/1758-5996-5-29. eCollection 2013. PMID: 23725555; PMCID: PMC3679947.
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Diabetol Metab Syndr. 2013 May 31;5:29. doi: 10.1186/1758-5996-5-29. eCollection 2013.

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

Diabetology & metabolic syndrome

Bradley S Henriksen, Mary E Curtis, Natasha Fillmore, Brandon R Cardon, David M Thomson, Chad R Hancock

Affiliations

  1. Department of Nutrition, Dietetics, and Food Science, Brigham Young University, Provo, UT 84602, USA.
  2. Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.

PMID: 23725555 PMCID: PMC3679947 DOI: 10.1186/1758-5996-5-29

Abstract

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.

Keywords: AMPK; GPAT1; LCAD; SREBP-1c; mTOR

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