Basic Research
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Jul 28, 2008; 14(28): 4462-4472
Published online Jul 28, 2008. doi: 10.3748/wjg.14.4462
Metabolomic changes in fatty liver can be modified by dietary protein and calcium during energy restriction
Taru K Pilvi, Tuulikki Seppänen-Laakso, Helena Simolin, Piet Finckenberg, Anne Huotari, Karl-Heinz Herzig, Riitta Korpela, Matej Orešič, Eero M Mervaala
Taru K Pilvi, Piet Finckenberg, Riitta Korpela, Eero M Mervaala, Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, PO Box 63, FI-00014 University of Helsinki, Helsinki FI-00390, Finland
Taru K Pilvi, Riitta Korpela, Foundation for Nutrition Research, PO Box 30, Helsinki FI-00390, Finland; Valio Ltd, Research Center, PO Box 30, Valio, Helsinki FI-00039, Finland
Tuulikki Seppänen-Laakso, Helena Simolin, Matej Orešič, VTT Technical Research Centre of Finland, Tietotie 2, VTT FI-02044, Finland
Anne Huotari, Karl-Heinz Herzig, A. I. Virtanen Institute for Molecular Sciences, PO Box 1627, University of Kuopio, Kuopio FI-70211, Finland
Karl-Heinz Herzig, Department of Internal Medicine, Kuopio University Hospital, PO Box 1777, Kuopio FI-70211, Finland; Institute of Biomedicine, Department of Physiology, and Biocenter of Oulu PO Box 5000, University of Oulu, Oulu FI-90014, Finland
Author contributions: Pilvi TK designed and conducted the study, analysed the data and prepared the manuscript. Seppänen-Laakso T, Simolin H and Orešič M did the metabolomic analyses. Huotari A and Herzig KH conducted the metabolic performance and calorimetry tests. Korpela R and Mervaala EM were involved in designing the study, reviewing and interpreting the results and all authors were involved in drafting the manuscript.
Correspondence to: Eero M Mervaala, MD, Professor, Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, PO Box 63, University of Helsinki, Helsinki FI-00390, Finland. eero.mervaala@helsinki.fi
Telephone: +358-9-19125355
Fax: +358-9-19125364
Received: April 16, 2008
Revised: June 23, 2008
Accepted: June 30, 2008
Published online: July 28, 2008
Abstract

AIM: To characterise the effect of energy restriction (ER) on liver lipid and primary metabolite profile by using metabolomic approach. We also investigated whether the effect of energy restriction can be further enhanced by modification of dietary protein source and calcium.

METHODS: Liver metabolomic profile of lean and obese C57Bl/6J mice (n = 10/group) were compared with two groups of weight-reduced mice. ER was performed on control diet and whey protein-based high-calcium diet (whey + Ca). The metabolomic analyses were performed using the UPLC/MS based lipidomic platform and the HPLC/MS/MS based primary metabolite platform.

RESULTS: ER on both diets significantly reduced hepatic lipid accumulation and lipid droplet size, while only whey + Ca diet significantly decreased blood glucose (P < 0.001) and serum insulin (P < 0.01). In hepatic lipid species the biggest reduction was in the level of triacylglycerols and ceramides while the level of cholesterol esters was significantly increased during ER. Interestingly, diacylglycerol to phospholipid ratio, an indicator of relative amount of diabetogenic diglyceride species, was increased in the control ER group, but decreased in the whey + Ca ER group (P < 0.001, vs obese). ER on whey + Ca diet also totally reversed the obesity induced increase in the relative level of lipotoxic ceramides (P < 0.001, vs obese; P > 0.05, vs lean). These changes were accompanied with up-regulated TCA cycle and pentose phosphate pathway metabolites.

CONCLUSION: ER-induced changes on hepatic metabolomic profile can be significantly affected by dietary protein source. The therapeutic potential of whey protein and calcium should be further studied.

Keywords: Fatty liver; Metabolomics; Energy restriction; Whey protein; Dietary calcium