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.
authors.affiliation: National Institute of Nutrition and Seafood Research, 5817 Bergen, Norway.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Liaset
authors.forename: Qin
authors.initials: Q
authors.lastname: Hao
authors.forename: Henry
authors.initials: H
authors.lastname: Jørgensen
authors.forename: Philip
authors.initials: P
authors.lastname: Hallenborg
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Du
authors.forename: Tao
authors.initials: T
authors.lastname: Ma
authors.forename: Hanns-Ulrich
authors.initials: HU
authors.lastname: Marschall
authors.forename: Mogens
authors.initials: M
authors.lastname: Kruhøffer
authors.forename: Ruiqiang
authors.initials: R
authors.lastname: Li
authors.forename: Qibin
authors.initials: Q
authors.lastname: Li
authors.forename: Christian Clement
authors.initials: CC
authors.lastname: Yde
authors.forename: Gabriel
authors.initials: G
authors.lastname: Criales
authors.forename: Hanne C
authors.initials: HC
authors.lastname: Bertram
authors.forename: Gunnar
authors.initials: G
authors.lastname: Mellgren
authors.forename: Erik Snorre
authors.initials: ES
authors.lastname: Ofjord
authors.forename: Erik-Jan
authors.initials: EJ
authors.lastname: Lock
authors.forename: Marit
authors.initials: M
authors.lastname: Espe
authors.forename: Livar
authors.initials: L
authors.lastname: Frøyland
authors.forename: Lise
authors.initials: L
authors.lastname: Madsen
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000378:metabolism; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D004044:Dietary Proteins / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007453:Iodide Peroxidase / Q000378:metabolism; D007473:Ion Channels; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D024821:Metabolic Syndrome / Q000097:blood / Q000178:diet therapy* / Q000378:metabolism*; D051379:Mice; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D048068:PPAR-beta / Q000378:metabolism; D000070780:Perilipin-2; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012474:Salmon; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D000071256:Uncoupling Protein 1; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D001647:Bile Acids and Salts; D004044:Dietary Proteins; D005947:Glucose; D006360:Heat-Shock Proteins; D007453:Iodide Peroxidase; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D048068:PPAR-beta; D000070780:Perilipin-2; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D014157:Transcription Factors; D014280:Triglycerides; D000071256:Uncoupling Protein 1; D000097564:Iodothyronine Deiodinase Type II; C474772:ANGPTL4 protein, human; C528241:ANGPTL4 protein, rat; C407088:Angptl4 protein, mouse; C000602982:PLIN2 protein, human; C486497:PPARGC1A protein, human; C000602983:Plin2 protein, mouse; C000602984:Plin2 protein, rat; C091778:Ppard protein, mouse; C485290:Ppargc1a protein, mouse; C501429:Ppargc1a protein, rat; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; C000604373:Ucp1 protein, rat