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 (Corresponding Author)

    Research output: Contribution to journalArticleScientificpeer-review

    23 Citations (Scopus)


    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.

    Original languageEnglish
    Pages (from-to)4462 - 4472
    Number of pages11
    JournalWorld Journal of Gastroenterology
    Issue number28
    Publication statusPublished - 2008
    MoE publication typeA1 Journal article-refereed


    • Fatty liver
    • metabolomics
    • energy restriction
    • whey protein
    • dietary calcium


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