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

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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.

Original languageEnglish
Pages (from-to)4462 - 4472
Number of pages11
JournalWorld Journal of Gastroenterology
Volume14
Issue number28
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

Fingerprint

Dietary Calcium
Metabolomics
Dietary Proteins
Fatty Liver
Liver
Diet
Diglycerides
Lipids
Calcium
Pentose Phosphate Pathway
Cholesterol Esters
Ceramides
Blood Glucose
Phospholipids
Triglycerides
High Pressure Liquid Chromatography
Insulin
Weights and Measures
Serum
Whey

Keywords

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

Cite this

Pilvi, Taru K. ; Seppänen-Laakso, Tuulikki ; Simolin, Helena ; Finckenberg, Piet ; Huotari, Anne ; Herzig, Karl-Heinz ; Korpela, Riitta ; Orešič, Matej ; Mervaala, Eero M. / Metabolomic changes in fatty liver can be modified by dietary protein and calcium during energy restriction. In: World Journal of Gastroenterology. 2008 ; Vol. 14, No. 28. pp. 4462 - 4472.
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title = "Metabolomic changes in fatty liver can be modified by dietary protein and calcium during energy restriction",
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",
author = "Pilvi, {Taru K.} and Tuulikki Sepp{\"a}nen-Laakso and Helena Simolin and Piet Finckenberg and Anne Huotari and Karl-Heinz Herzig and Riitta Korpela and Matej Orešič and Mervaala, {Eero M.}",
year = "2008",
doi = "10.3748/wjg.14.4462",
language = "English",
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pages = "4462 -- 4472",
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Pilvi, TK, Seppänen-Laakso, T, Simolin, H, Finckenberg, P, Huotari, A, Herzig, K-H, Korpela, R, Orešič, M & Mervaala, EM 2008, 'Metabolomic changes in fatty liver can be modified by dietary protein and calcium during energy restriction', World Journal of Gastroenterology, vol. 14, no. 28, pp. 4462 - 4472. https://doi.org/10.3748/wjg.14.4462

Metabolomic changes in fatty liver can be modified by dietary protein and calcium during energy restriction. / Pilvi, Taru K.; Seppänen-Laakso, Tuulikki; Simolin, Helena; Finckenberg, Piet; Huotari, Anne; Herzig, Karl-Heinz; Korpela, Riitta; Orešič, Matej; Mervaala, Eero M. (Corresponding Author).

In: World Journal of Gastroenterology, Vol. 14, No. 28, 2008, p. 4462 - 4472.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Metabolomic changes in fatty liver can be modified by dietary protein and calcium during energy restriction

AU - Pilvi, Taru K.

AU - Seppänen-Laakso, Tuulikki

AU - Simolin, Helena

AU - Finckenberg, Piet

AU - Huotari, Anne

AU - Herzig, Karl-Heinz

AU - Korpela, Riitta

AU - Orešič, Matej

AU - Mervaala, Eero M.

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

KW - Fatty liver

KW - metabolomics

KW - energy restriction

KW - whey protein

KW - dietary calcium

U2 - 10.3748/wjg.14.4462

DO - 10.3748/wjg.14.4462

M3 - Article

VL - 14

SP - 4462

EP - 4472

JO - World Journal of Gastroenterology

JF - World Journal of Gastroenterology

SN - 1007-9327

IS - 28

ER -