Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome

Bjørn Liaset; Qin Hao; Henry Johs. Høgh Jørgensen; Philip Hallenborg; Zhen-Yu Du; Tao Ma; Hanns-Ulrich Marschall; Mogens Kruhøffer; Ruiqiang Li; Qibin Li; Christian Clement Yde; Gabriel Criales; Hanne Christine S. Bertram; Gunnar Mellgren; Erik Snorre Ofjord; Erik-Jan Lock; Marit Espe; Livar Frøyland; Lise Madsen; Karsten Kristiansen

doi:10.1074/jbc.M111.234732

Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome

Bjørn Liaset, Qin Hao, Henry Johs. Høgh Jørgensen, Philip Hallenborg, Zhen-Yu Du, Tao Ma, Hanns-Ulrich Marschall, Mogens Kruhøffer, Ruiqiang Li, Qibin Li, Christian Clement Yde, Gabriel Criales, Hanne Christine S. Bertram, Gunnar Mellgren, Erik Snorre Ofjord, Erik-Jan Lock, Marit Espe, Livar Frøyland, Lise Madsen, Karsten Kristiansen

Department of Biology

50 Citations (Scopus)

Abstract

Bile acids (BAs) are powerful regulators of metabolism, and mice treated orally with cholic acid are protected from diet-induced obesity, hepatic lipid accumulation, and increased plasma triacylglycerol (TAG) and glucose levels. Here, we show that plasma BA concentration in rats was elevated by exchanging the dietary protein source from casein to salmon protein hydrolysate (SPH). Importantly, the SPH-treated rats were resistant to diet-induced obesity. SPH-treated rats had reduced fed state plasma glucose and TAG levels and lower TAG in liver. The elevated plasma BA concentration was associated with induction of genes involved in energy metabolism and uncoupling, Dio2, Pgc-1α, and Ucp1, in interscapular brown adipose tissue. Interestingly, the same transcriptional pattern was found in white adipose tissue depots of both abdominal and subcutaneous origin. Accordingly, rats fed SPH-based diet exhibited increased whole body energy expenditure and heat dissipation. In skeletal muscle, expressions of the peroxisome proliferator-activated receptor β/δ target genes (Cpt-1b, Angptl4, Adrp, and Ucp3) were induced. Pharmacological removal of BAs by inclusion of 0.5 weight % cholestyramine to the high fat SPH diet attenuated the reduction in abdominal obesity, the reduction in liver TAG, and the decrease in nonfasted plasma TAG and glucose levels. Induction of Ucp3 gene expression in muscle by SPH treatment was completely abolished by cholestyramine inclusion. Taken together, our data provide evidence that bile acid metabolism can be modulated by diet and that such modulation may prevent/ameliorate the characteristic features of the metabolic syndrome.

Original language	English
Journal	The Journal of Biological Chemistry
Volume	286
Issue number	32
Pages (from-to)	28382-95
Number of pages	14
ISSN	1083-351X
DOIs	https://doi.org/10.1074/jbc.M111.234732
Publication status	Published - 12 Aug 2011

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10.1074/jbc.M111.234732

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Liaset, B., Hao, Q., Jørgensen, H. J. H., Hallenborg, P., Du, Z-Y., Ma, T., Marschall, H-U., Kruhøffer, M., Li, R., Li, Q., Yde, C. C., Criales, G., Bertram, H. C. S., Mellgren, G., Ofjord, E. S., Lock, E-J., Espe, M., Frøyland, L., Madsen, L., & Kristiansen, K. (2011). Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome. The Journal of Biological Chemistry, 286(32), 28382-95. https://doi.org/10.1074/jbc.M111.234732

Liaset, B, Hao, Q, Jørgensen, HJH, Hallenborg, P, Du, Z-Y, Ma, T, Marschall, H-U, Kruhøffer, M, Li, R, Li, Q, Yde, CC, Criales, G, Bertram, HCS, Mellgren, G, Ofjord, ES, Lock, E-J, Espe, M, Frøyland, L, Madsen, L & Kristiansen, K 2011, 'Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome', The Journal of Biological Chemistry, vol. 286, no. 32, pp. 28382-95. https://doi.org/10.1074/jbc.M111.234732

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title = "Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome",

abstract = "Bile acids (BAs) are powerful regulators of metabolism, and mice treated orally with cholic acid are protected from diet-induced obesity, hepatic lipid accumulation, and increased plasma triacylglycerol (TAG) and glucose levels. Here, we show that plasma BA concentration in rats was elevated by exchanging the dietary protein source from casein to salmon protein hydrolysate (SPH). Importantly, the SPH-treated rats were resistant to diet-induced obesity. SPH-treated rats had reduced fed state plasma glucose and TAG levels and lower TAG in liver. The elevated plasma BA concentration was associated with induction of genes involved in energy metabolism and uncoupling, Dio2, Pgc-1α, and Ucp1, in interscapular brown adipose tissue. Interestingly, the same transcriptional pattern was found in white adipose tissue depots of both abdominal and subcutaneous origin. Accordingly, rats fed SPH-based diet exhibited increased whole body energy expenditure and heat dissipation. In skeletal muscle, expressions of the peroxisome proliferator-activated receptor β/δ target genes (Cpt-1b, Angptl4, Adrp, and Ucp3) were induced. Pharmacological removal of BAs by inclusion of 0.5 weight % cholestyramine to the high fat SPH diet attenuated the reduction in abdominal obesity, the reduction in liver TAG, and the decrease in nonfasted plasma TAG and glucose levels. Induction of Ucp3 gene expression in muscle by SPH treatment was completely abolished by cholestyramine inclusion. Taken together, our data provide evidence that bile acid metabolism can be modulated by diet and that such modulation may prevent/ameliorate the characteristic features of the metabolic syndrome.",

author = "Bj{\o}rn Liaset and Qin Hao and J{\o}rgensen, {Henry Johs. H{\o}gh} and Philip Hallenborg and Zhen-Yu Du and Tao Ma and Hanns-Ulrich Marschall and Mogens Kruh{\o}ffer and Ruiqiang Li and Qibin Li and Yde, {Christian Clement} and Gabriel Criales and Bertram, {Hanne Christine S.} and Gunnar Mellgren and Ofjord, {Erik Snorre} and Erik-Jan Lock and Marit Espe and Livar Fr{\o}yland and Lise Madsen and Karsten Kristiansen",

year = "2011",

month = aug,

day = "12",

doi = "10.1074/jbc.M111.234732",

language = "English",

volume = "286",

pages = "28382--95",

journal = "Journal of Biological Chemistry",

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publisher = "American Society for Biochemistry and Molecular Biology, Inc.",

number = "32",

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TY - JOUR

T1 - Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome

AU - Liaset, Bjørn

AU - Hao, Qin

AU - Jørgensen, Henry Johs. Høgh

AU - Hallenborg, Philip

AU - Du, Zhen-Yu

AU - Ma, Tao

AU - Marschall, Hanns-Ulrich

AU - Kruhøffer, Mogens

AU - Li, Ruiqiang

AU - Li, Qibin

AU - Yde, Christian Clement

AU - Criales, Gabriel

AU - Bertram, Hanne Christine S.

AU - Mellgren, Gunnar

AU - Ofjord, Erik Snorre

AU - Lock, Erik-Jan

AU - Espe, Marit

AU - Frøyland, Livar

AU - Madsen, Lise

AU - Kristiansen, Karsten

PY - 2011/8/12

Y1 - 2011/8/12

N2 - Bile acids (BAs) are powerful regulators of metabolism, and mice treated orally with cholic acid are protected from diet-induced obesity, hepatic lipid accumulation, and increased plasma triacylglycerol (TAG) and glucose levels. Here, we show that plasma BA concentration in rats was elevated by exchanging the dietary protein source from casein to salmon protein hydrolysate (SPH). Importantly, the SPH-treated rats were resistant to diet-induced obesity. SPH-treated rats had reduced fed state plasma glucose and TAG levels and lower TAG in liver. The elevated plasma BA concentration was associated with induction of genes involved in energy metabolism and uncoupling, Dio2, Pgc-1α, and Ucp1, in interscapular brown adipose tissue. Interestingly, the same transcriptional pattern was found in white adipose tissue depots of both abdominal and subcutaneous origin. Accordingly, rats fed SPH-based diet exhibited increased whole body energy expenditure and heat dissipation. In skeletal muscle, expressions of the peroxisome proliferator-activated receptor β/δ target genes (Cpt-1b, Angptl4, Adrp, and Ucp3) were induced. Pharmacological removal of BAs by inclusion of 0.5 weight % cholestyramine to the high fat SPH diet attenuated the reduction in abdominal obesity, the reduction in liver TAG, and the decrease in nonfasted plasma TAG and glucose levels. Induction of Ucp3 gene expression in muscle by SPH treatment was completely abolished by cholestyramine inclusion. Taken together, our data provide evidence that bile acid metabolism can be modulated by diet and that such modulation may prevent/ameliorate the characteristic features of the metabolic syndrome.

AB - Bile acids (BAs) are powerful regulators of metabolism, and mice treated orally with cholic acid are protected from diet-induced obesity, hepatic lipid accumulation, and increased plasma triacylglycerol (TAG) and glucose levels. Here, we show that plasma BA concentration in rats was elevated by exchanging the dietary protein source from casein to salmon protein hydrolysate (SPH). Importantly, the SPH-treated rats were resistant to diet-induced obesity. SPH-treated rats had reduced fed state plasma glucose and TAG levels and lower TAG in liver. The elevated plasma BA concentration was associated with induction of genes involved in energy metabolism and uncoupling, Dio2, Pgc-1α, and Ucp1, in interscapular brown adipose tissue. Interestingly, the same transcriptional pattern was found in white adipose tissue depots of both abdominal and subcutaneous origin. Accordingly, rats fed SPH-based diet exhibited increased whole body energy expenditure and heat dissipation. In skeletal muscle, expressions of the peroxisome proliferator-activated receptor β/δ target genes (Cpt-1b, Angptl4, Adrp, and Ucp3) were induced. Pharmacological removal of BAs by inclusion of 0.5 weight % cholestyramine to the high fat SPH diet attenuated the reduction in abdominal obesity, the reduction in liver TAG, and the decrease in nonfasted plasma TAG and glucose levels. Induction of Ucp3 gene expression in muscle by SPH treatment was completely abolished by cholestyramine inclusion. Taken together, our data provide evidence that bile acid metabolism can be modulated by diet and that such modulation may prevent/ameliorate the characteristic features of the metabolic syndrome.

U2 - 10.1074/jbc.M111.234732

DO - 10.1074/jbc.M111.234732

M3 - Journal article

C2 - 21680746

SN - 0021-9258

VL - 286

SP - 28382

EP - 28395

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 32

ER -

Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome

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