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 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.

A fish protein hydrolysate alters fatty acid composition in liver and adipose tissue and increases plasma carnitine levels in a mouse model of chronic inflammation

“…The supernatant was filtered and amino acids were characterised by a Biochrom 20 plus amino acid analyser as previously described [29]. …”

Indomethacin Treatment Prevents High Fat Diet-induced Obesity and Insulin Resistance but Not Glucose Intolerance in C57BL/6J Mice

“…Histology Examinations-Paraffin-embedded sections of epididymal white adipose tissue (eWAT) and iWAT were stained with hematoxylin and eosin and analyzed as described previously (12). Sections of pancreatic tissue were stained for insulin, and pancreatic islet and section sizes were analyzed (13).…”

“…After 6 weeks of treatment with the respective diets, total lipid was extracted from feces collected for 48 h (12).…”

Dietary Regulation of Mouse Intestinal P450 Expression and Drug Metabolism

“…(A) Immunoblot analysis of CYP3A expression was performed as described in Fig dmd.aspetjournals.org although the total protein or fiber content (percentage) in the two diets is similar, the types of proteins and fibers differ by diet. Previous studies have shown that changes in dietary constituents, including fiber contents (Kritchevsky, 1978) and protein sources (Liaset et al, 2011), can influence size of the BA pool. Here, we further demonstrated, for the first time, that the change from the regular chow to the synthetic diet causes large decreases in all five major murine BAs in plasma, liver, SI, and intestinal content.…”