99 BILE ACIDS PREVENT FRUCTOSE-INDUCED HEPATIC STEATOSIS

Aim. To estimate the blood levels of primary, secondary, tertiary and unconjugated bile acids in patients with non-alcoholic fatty liver disease.Methods. The study included 74 patients with non-alcoholic fatty liver disease (males - 30, females - 44) and 51 healthy individuals (males - 14, females - 37). All patients underwent anthropometry and complete clinical, biochemical and instrumental examination (measuring the subcutaneous fat layer). 64 patients had hepatic steatosis, 10 - steatohepatitis. Serum levels of bile acids (primary: cholic, chenodeoxycholic; secondary: lithocholic, deoxycholic and tertiary: ursodeoxycholic) were measured by gas-liquid chromatography on «Chromos GC-1000» (Russia) scanner.Results. Unconjugated primary, secondary and tertiary bile acids were detected in the blood of healthy individuals and patients with non-alcoholic fatty liver disease. In healthy individuals, there were no gender differences found in the bile acids levels. Patients with non-alcoholic fatty liver disease had higher level of bile acids compared to healthy controls. There was a significant difference in the concentrations of secondary and tertiary bile acids in patients with hepatic steatosis and steatohepatitis.Conclusion. Blood bile acids levels were significantly higher in patients with non-alcoholic fatty liver disease than in healthy individuals. At steatohepatitis, females had higher levels of cholic, chenodeoxycholic and deoxycholic acids and lower levels of lithocholic and ursodeoxycholic acids compared to males. Significant difference in patients with hepatic steatosis and steatohepatitis was revealed only in levels of secondary and tertiary bile acids.

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Low production of 12α-hydroxylated bile acids prevents hepatic steatosis in Cyp2c70-/- mice by reducing fat absorption

The Journal of Lipid Research ◽

10.1016/j.jlr.2021.100134 ◽

2021 ◽

pp. 100134

Author(s):

Rumei Li ◽

Anna Palmiotti ◽

Hilde D. de Vries ◽

Milaine V. Hovingh ◽

Martijn Koehorst ◽

...

Keyword(s):

Bile Acids ◽

Hepatic Steatosis ◽

Fat Absorption

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Protective effect of bile acids on the onset of fructose-induced hepatic steatosis in mice

The Journal of Lipid Research ◽

10.1194/jlr.m007179 ◽

2010 ◽

Vol 51 (12) ◽

pp. 3414-3424 ◽

Cited By ~ 32

Author(s):

Valentina Volynets ◽

Astrid Spruss ◽

Giridhar Kanuri ◽

Sabine Wagnerberger ◽

Stephan C. Bischoff ◽

...

Keyword(s):

Protective Effect ◽

Bile Acids ◽

Hepatic Steatosis

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Association between 12α-hydroxylated bile acids and hepatic steatosis in rats fed a high-fat diet

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2020.108412 ◽

2020 ◽

Vol 83 ◽

pp. 108412

Author(s):

Shota Hori ◽

Takayuki Abe ◽

Dong Geun Lee ◽

Satoru Fukiya ◽

Atsushi Yokota ◽

...

Keyword(s):

Bile Acids ◽

Hepatic Steatosis ◽

High Fat Diet ◽

High Fat

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Vertical sleeve gastrectomy reduces hepatic steatosis while increasing serum bile acids in a weight-loss-independent manner

Obesity ◽

10.1002/oby.20548 ◽

2013 ◽

Vol 22 (2) ◽

pp. 390-400 ◽

Cited By ~ 121

Author(s):

Andriy Myronovych ◽

Michelle Kirby ◽

Karen K. Ryan ◽

Wujuan Zhang ◽

Pinky Jha ◽

...

Keyword(s):

Weight Loss ◽

Sleeve Gastrectomy ◽

Bile Acids ◽

Hepatic Steatosis ◽

Vertical Sleeve Gastrectomy ◽

Independent Manner ◽

Serum Bile Acids

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50 Sleeve Gastrectomy in Obese Mice Results in Elevated Serum Bile Acids and Reduced Hepatic Steatosis That Correlate With Weight Loss Post Surgery

Gastroenterology ◽

10.1016/s0016-5085(12)60050-x ◽

2012 ◽

Vol 142 (5) ◽

pp. S-13 ◽

Cited By ~ 3

Author(s):

Andriy Myronovych ◽

Michelle Kirby ◽

Randy J. Seeley ◽

Rohit Kohli

Keyword(s):

Weight Loss ◽

Sleeve Gastrectomy ◽

Bile Acids ◽

Hepatic Steatosis ◽

Elevated Serum ◽

Obese Mice ◽

Serum Bile Acids ◽

Post Surgery

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A Surgical Model in Male Obese Rats Uncovers Protective Effects of Bile Acids Post-Bariatric Surgery

Endocrinology ◽

10.1210/en.2012-2069 ◽

2013 ◽

Vol 154 (7) ◽

pp. 2341-2351 ◽

Cited By ~ 96

Author(s):

Rohit Kohli ◽

Kenneth DR Setchell ◽

Michelle Kirby ◽

Andriy Myronovych ◽

Karen K. Ryan ◽

...

Keyword(s):

Bariatric Surgery ◽

Bile Acid ◽

Glucose Tolerance ◽

Er Stress ◽

Bile Acids ◽

Hepatic Steatosis ◽

Homologous Protein ◽

Obese Rats ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Abstract Bariatric surgery elevates serum bile acids. Conjugated bile acid administration, such as tauroursodeoxycholic acid (TUDCA), improves insulin sensitivity, whereas short-circuiting bile acid circulation through ileal interposition surgery in rats raises TUDCA levels. We hypothesized that bariatric surgery outcomes could be recapitulated by short circuiting the normal enterohepatic bile circulation. We established a model wherein male obese rats underwent either bile diversion (BD) or Sham (SH) surgery. The BD group had a catheter inserted into the common bile duct and its distal end anchored into the middistal jejunum for 4–5 weeks. Glucose tolerance, insulin and glucagon-like peptide-1 (GLP-1) response, hepatic steatosis, and endoplasmic reticulum (ER) stress were measured. Rats post-BD lost significantly more weight than the SH rats. BD rats gained less fat mass after surgery. BD rats had improved glucose tolerance, increased higher postprandial glucagon-like peptide-1 response and serum bile acids but less liver steatosis. Serum bile acid levels including TUDCA concentrations were higher in BD compared to SH pair-fed rats. Fecal bile acid levels were not different. Liver ER stress (C/EBP homologous protein mRNA and pJNK protein) was decreased in BD rats. Bile acid gavage (TUDCA/ursodeoxycholic acid [UDCA]) in diet-induced obese rats, elevated serum TUDCA and concomitantly reduced hepatic steatosis and ER stress (C/EBP homologous protein mRNA). These data demonstrate the ability of alterations in bile acids to recapitulate important metabolic improvements seen after bariatric surgery. Further, our work establishes a model for focused study of bile acids in the context of bariatric surgery that may lead to the identification of therapeutics for metabolic disease.

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Inulin Improves Insulin Sensitivity, Changes Cecal Bile Acids, but Does Not Mitigate Hepatic Steatosis from an Obesogenic, High Fat Diet

Current Developments in Nutrition ◽

10.1093/cdn/nzaa049_048 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 655-655

Author(s):

Bret Rust ◽

Joseph Idso ◽

Bryan Safratowich ◽

Michael Bukowski ◽

Huawei Zeng ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Bile Acids ◽

Hepatic Steatosis ◽

Fatty Acid Content ◽

Chain Polyunsaturated Fatty Acid ◽

High Fat ◽

Funding Sources ◽

Polyunsaturated Fatty Acid Content ◽

Signaling Axis

Abstract Objectives Obesogenic, high fat diets (HFD) increase hepatic long chain polyunsaturated fatty acid content (LCPUFA), but also lead to hepatic steatosis and insulin resistance. Fermentable fiber such as inulin (INU) may reduce these negative outcomes via a bile acid (BA)-liver signaling axis. This study tests the hypothesis that INU maintains elevated LCPUFA but reduces HFD-induced insulin resistance and fatty liver and investigates the potential relationship of bile acids. Methods Male mice (4 wk) were fed a low fat diet (LFD) (16% en fat) or HFD (48% en fat) containing 10% non-fermentable cellulose (CL) or 3% CL and 7% INU for 13 wks in a 2 × 2 factorial design. Tissue, plasma, and cecal contents were collected week 13. Results Intake of the HFD-CL increased hepatic LCPUFA content and steatosis and reduced insulin sensitivity vs LFD treatments. INU maintained HFD-induced LCPUFA elevation, improved insulin sensitivity, due to reductions in fasting glucose, but did not mitigate HFD-induced hepatic steatosis. When standardized to the hepatic triacylglycerol (TAG) content, LCPUFA (notably 22:6n-3) were increased by INU in the LFD only. The BAs with highest cecal concentrations were deoxycholic (DCA) and beta/omega murine cholic (B/OMCA) acids. INU increased cecal wt and decreased concentrations of DCA and B/OMCA. INU-induced B/OMCA reductions were enhanced by the HFD, but the DCA effects were independent of % en fat. The expression of multiple lipid metabolic genes was assessed. Of these, reductions in Scd1 expression occurred with both HFD and INU treatments compared to LFD-CL. SREBP1c, Fasn, Scd1, Elov5, Fads1, and Fads2 correlated with murine cholic acids and cholic acid in HFD-INU but only weakly in LFD-INU. These relationships were not evident with the CL-based diets. Conclusions INU in an HFD provided mixed outcomes by maintaining elevated hepatic LCPUFA, reducing fasting plasma glucose concentrations but failing to reduce fasting insulin concentrations and hepatic steatosis. While cecal BAs and hepatic gene expression correlated with the INU treatments, these mechanistic changes did not mitigate HFD-induced hepatic steatosis. Funding Sources USDA-ARS.

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