Bile secretory function in the obese Zucker rat: evidence of cholestasis and altered canalicular transport function

Pizarro, Margarita; Balasubramaniyan, Natarajan; Solı́s, Nancy; Solar, Antonieta; Duarte, Isabella de Araújo Esteves; Miquel, Juan Francisco; Suchy, Frederick J.; Trauner, Michael; Accatino, Luigi; Ananthanarayanan, Meenakshisundaram; Arrese, Marco

doi:10.1136/gut.2003.037689

Cited by 80 publications

(89 citation statements)

References 51 publications

(36 reference statements)

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“…However, a few recent publications support such a role for endogenous bile acid metabolism. Bile secretion is impaired in both the Zucker (fa/fa) rat (76) and in the ob/ob mice (77), FIGURE 6. Reduction in fed-state plasma glucose is attenuated by pharmacological removal of bile acids.…”

Section: Discussionmentioning

confidence: 99%

Nutritional Regulation of Bile Acid Metabolism Is Associated with Improved Pathological Characteristics of the Metabolic Syndrome

Liaset¹,

Qin

Jørgensen

et al. 2011

Journal of Biological Chemistry

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Bile acids (BAs) are powerful regulators of metabolism, and mice treated orally with cholic acid are protected from dietinduced 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-1␣, 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 proliferatoractivated receptor ␤/␦ 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.

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Section: Discussionmentioning

confidence: 99%

Nutritional Regulation of Bile Acid Metabolism Is Associated with Improved Pathological Characteristics of the Metabolic Syndrome

Liaset¹,

Qin

Jørgensen

et al. 2011

Journal of Biological Chemistry

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“…Hypoxia induces a down regulation of Bsep in rat and mouse liver [78,128]. Fatty liver disease in obsese Zucker rats is paralleled by a slight down regulation of Bsep [255], while in fatty livers of chronically ethanol fed rats, Bsep is upregulated at the mRNA and protein level [354]. Taken together, in animal models of liver injury, Bsep is only mildly affected at the expression level but may alter its subcellular localization [92,262].…”

Section: Pathophysiologymentioning

confidence: 99%

The Role of the Sodium-Taurocholate Cotransporting Polypeptide (NTCP) and of the Bile Salt Export Pump (BSEP) in Physiology and Pathophysiology of Bile Formation

Stieger

2010

Handbook of Experimental Pharmacology

246

260

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“…Though cholestasis is unusual in fatty acid oxidation disorders, it accompanies hepatic steatosis in a number of other genetic metabolic disorders, including mitochondrial liver disease, galactosaemia, tyrosinaemia type 1, Wilson disease and cystic fibrosis. Mild cholestasis also occurs in a rat model of non-alcoholic fatty liver disease (Pizarro et al 2004) but the pathogenesis is unlikely to resemble that in our patient.…”

Section: Discussionmentioning

confidence: 50%

Cholestatic Jaundice Associated with Carnitine Palmitoyltransferase IA Deficiency

et al. 2012

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Liver dysfunction usually accompanies metabolic decompensation in fatty acid oxidation disorders, including carnitine palmitoyltransferase (CPT) Ia deficiency. Typically, the liver is enlarged with raised plasma transaminase activities and steatosis on histological examination. In contrast, cholestatic jaundice is rare, having only been reported in long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. We report a 3-yearold boy with CPT Ia deficiency who developed hepatomegaly and cholestatic jaundice following a viral illness.

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Bile secretory function in the obese Zucker rat: evidence of cholestasis and altered canalicular transport function

Cited by 80 publications

References 51 publications

Nutritional Regulation of Bile Acid Metabolism Is Associated with Improved Pathological Characteristics of the Metabolic Syndrome

Nutritional Regulation of Bile Acid Metabolism Is Associated with Improved Pathological Characteristics of the Metabolic Syndrome

The Role of the Sodium-Taurocholate Cotransporting Polypeptide (NTCP) and of the Bile Salt Export Pump (BSEP) in Physiology and Pathophysiology of Bile Formation

Cholestatic Jaundice Associated with Carnitine Palmitoyltransferase IA Deficiency

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