Metabolomic changes in fatty liver can be modified by dietary protein and calcium during energy restriction

• Published in: World journal of gastroenterology : WJG Vol. 14; no. 28; pp. 4462 - 4472
• Main Authors: Pilvi, Taru-K, Seppanen-Laakso, Tuulikki, Simolin, Helena, Finckenberg, Piet, Huotari, Anne, Herzig, Karl-Heinz, Korpela, Riitta, Oresic, Matej, Mervaala, Eero-M
• Format: Journal Article
• Language: English
• Published: United States Department of Internal Medicine,Kuopio University Hospital,PO Box 1777,Kuopio FI-70211,Finland 28.07.2008; Foundation for Nutrition Research,PO Box 30,Helsinki FI-00390,Finland%Institute of Biomedicine,Pharmacology,Biomedicum Helsinki,PO Box 63,FI-00014 University of Helsinki,elsinki FI-00390, Finland; Institute of Biomedicine,Department of Physiology,and Biocenter of Oulu PO Box 5000,University of Oulu,Oulu FI-90014,Finland%Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, PO Box 63, FI-00014 University of Helsinki,elsinki FI-00390,Finland; Foundation for Nutrition Research,PO Box 30,Helsinki FI-00390,Finland%VTT Technical Research Centre of Finland,Tietotie 2,VTT FI-02044,Finland%Institute of Biomedicine,Pharmacology, Biomedicum Helsinki,PO Box 63,FI-00014 University of Helsinki,Helsinki FI-00390,Finland%A.I.Virtanen Institute for Molecular Sciences,PO Box 1627,University of Kuopio,Kuopio FI-70211,Finland%A.I.Virtanen Institute for Molecular Sciences,PO Box 1627,University of Kuopio,Kuopio FI-70211, Finland; Institute of Biomedicine,Pharmacology,Biomedicum Helsinki,PO Box 63,FI-00014 University of Helsinki,elsinki FI-00390,Finland; The WJG Press and Baishideng
• Subjects: Animals; Basic Research; Blood Glucose - metabolism; Body Weight - drug effects; Body Weight - physiology; Calcium, Dietary - pharmacology; dietary calcium; Dietary Proteins - pharmacology; Disease Models, Animal; Energy Metabolism - physiology; energy restriction; Fatty liver; Fatty Liver - metabolism; Fatty Liver - physiopathology; Insulin - blood; Lipid Metabolism - drug effects; Lipid Metabolism - physiology; Liver - metabolism; Liver - pathology; Male; metabolomics; Mice; Mice, Inbred C57BL; whey protein; 能量限制; 脂肪肝; 蛋白质; 钙离子; 饮食调节; Energy restriction; Metabolomics; Dietary calcium; Fatty liver; Whey protein
• DOI: 10.3748/wjg.14.4462
• ISSN: 1007-9327; 2219-2840

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 C57BI/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 cerarnides 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 cerarnides （P 〈 0.001, vs obese; P 〉 0.05, vs lean）. These changes were accompanied with up-regulated TCA cycle and pentose phosphate pathway rnetabolites. CONCLUSION： ER-induced changes on hepatic rnetabolornic profile can be significantly affected by dietary protein source. The therapeutic potential of whey protein and calcium should be further studied.