title: Metabolomic changes in fatty liver can be modified by dietary protein and calcium during energy restriction.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Helsinki, Helsinki FI-00390, Finland.
authors.forename: Taru-K
authors.initials: TK
authors.lastname: Pilvi
authors.forename: Tuulikki
authors.initials: T
authors.lastname: Seppanen-Laakso
authors.forename: Helena
authors.initials: H
authors.lastname: Simolin
authors.forename: Piet
authors.initials: P
authors.lastname: Finckenberg
authors.forename: Anne
authors.initials: A
authors.lastname: Huotari
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Herzig
authors.forename: Riitta
authors.initials: R
authors.lastname: Korpela
authors.forename: Matej
authors.initials: M
authors.lastname: Oresic
authors.forename: Eero-M
authors.initials: EM
authors.lastname: Mervaala
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002136:Calcium, Dietary / Q000494:pharmacology*; D004044:Dietary Proteins / Q000494:pharmacology*; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology*; D005234:Fatty Liver / Q000378:metabolism* / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001786:Blood Glucose; D002136:Calcium, Dietary; D004044:Dietary Proteins; D007328:Insulin