Open Access Highly Accessed Research article

Linking nutritional regulation of Angptl4, Gpihbp1, and Lmf1 to lipoprotein lipase activity in rodent adipose tissue

Olessia Kroupa1, Evelina Vorrsjö1, Rinke Stienstra2, Frits Mattijssen2, Stefan K Nilsson1, Valentina Sukonina13, Sander Kersten2, Gunilla Olivecrona1 and Thomas Olivecrona1*

Author affiliations

1 Department of Medical Biosciences/Physiological Chemistry, Umeå University, Umeå, SE-90187, Sweden

2 Nutrition, Metabolism and Genomics group, Division of Human Nutrition, Wageningen University, Wageningen, 6700EV, The Netherlands

3 Present address: Department of Medicine, University of Gothenburg, Gothenburg, SE-405 30, Sweden

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Citation and License

BMC Physiology 2012, 12:13  doi:10.1186/1472-6793-12-13

Published: 23 November 2012

Abstract

Background

Lipoprotein lipase (LPL) hydrolyzes triglycerides in lipoproteins and makes fatty acids available for tissue metabolism. The activity of the enzyme is modulated in a tissue specific manner by interaction with other proteins. We have studied how feeding/fasting and some related perturbations affect the expression, in rat adipose tissue, of three such proteins, LMF1, an ER protein necessary for folding of LPL into its active dimeric form, the endogenous LPL inhibitor ANGPTL4, and GPIHBP1, that transfers LPL across the endothelium.

Results

The system underwent moderate circadian oscillations, for LPL in phase with food intake, for ANGPTL4 and GPIHBP1 in the opposite direction. Studies with cycloheximide showed that whereas LPL protein turns over rapidly, ANGPTL4 protein turns over more slowly. Studies with the transcription blocker Actinomycin D showed that transcripts for ANGPTL4 and GPIHBP1, but not LMF1 or LPL, turn over rapidly. When food was withdrawn the expression of ANGPTL4 and GPIHBP1 increased rapidly, and LPL activity decreased. On re-feeding and after injection of insulin the expression of ANGPTL4 and GPIHBP1 decreased rapidly, and LPL activity increased. In ANGPTL4−/− mice adipose tissue LPL activity did not show these responses. In old, obese rats that showed signs of insulin resistance, the responses of ANGPTL4 and GPIHBP1 mRNA and of LPL activity were severely blunted (at 26 weeks of age) or almost abolished (at 52 weeks of age).

Conclusions

This study demonstrates directly that ANGPTL4 is necessary for rapid modulation of LPL activity in adipose tissue. ANGPTL4 message levels responded very rapidly to changes in the nutritional state. LPL activity always changed in the opposite direction. This did not happen in Angptl4−/− mice. GPIHBP1 message levels also changed rapidly and in the same direction as ANGPTL4, i.e. increased on fasting when LPL activity decreased. This was unexpected because GPIHBP1 is known to stabilize LPL. The plasticity of the LPL system is severely blunted or completely lost in insulin resistant rats.

Keywords:
Gene expression; Insulin; Gene inactivation; Cycloheximide; Actinomycin D; Transcription; Translation; Posttranslational