Diet-induced obesity and weight loss alter bile acid concentrations and bile acid–sensitive gene expression in insulin target tissues of C57BL/6J mice

Frano, Michael R. La; Hernández-Carretero, Angelina; Weber, Natalie; Borkowski, Kamil; Pedersen, Theresa L.; Osborn, Olivia; Newman, John W.

doi:10.1016/j.nutres.2017.07.006

Cited by 47 publications

(41 citation statements)

References 42 publications

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“…Accompanied with the effect on expression and activation of CAR and PPARα, UGT1A1 and UGT1A6 expression levels were altered by the high fat diet [3]. Regarding transporters, gene expression level of Abcc3 was reduced by high fat diet [9].…”

Section: Introductionmentioning

confidence: 92%

High fat diet significantly changed the global gene expression profile involved in hepatic drug metabolism and pharmacokinetic system in mice

Yang

et al. 2020

Nutr Metab (Lond)

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Background: High fat diet impact transcription of hepatic genes responsible for drug metabolism and pharmacokinetics. Until now, researches just focused on a couple specific genes without a global profile showing. Age-dependent manner was also not noted well. This study aims to investigate the high fat diet effect on transcriptome of drug metabolism and pharmacokinetic system in mouse livers and show the age-dependent evidence. Methods: C57BL/6 male mice were used in this experiment. High fat diet was used to treat mice for 16 and 38 weeks. Serum total cholesterol, low density lipoprotein cholesterol, aspartate transaminase, and alanine transaminaselevels were measured. Meanwhile, Histology, RNA-Seq, RT-PCR analysis and fourteen major hepatic bile acids quantification were performed for the liver tissues. Data was mined at levels of genes, drug metabolism and pharmacokinetic sysem, and genome wide. Results: Treatment with high fat diet for 38 weeks significantly increased levels of serum lipids as well as aspartate transaminase, and alanine transaminase. Meanwhile, lipid accumulation in livers was observed. At week 38 of the experiment, the profile of 612 genes involved in drug metabolism and pharmacokinetics was significantly changed, indicated by a heatmap visulization and a principal component analysis. In total 210 genes were significantly regulated. Cyp3a11, Cyp4a10, and Cyp4a14 were down-regulated by 10-35 folds, while these three genes also were highly expressed in the liver. High fat diet regulated 11% of genome-wide gene while 30% of genes involved in the hepatic drug metabolism and pharmacokinetic system. Genes, including Adh4,

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Section: Introductionmentioning

confidence: 92%

High fat diet significantly changed the global gene expression profile involved in hepatic drug metabolism and pharmacokinetic system in mice

Yang

et al. 2020

Nutr Metab (Lond)

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“…when considering FXR agonism as a therapeutic strategy). Furthermore, it is important to note that these data, obtained in human tissues, appear to contrast with a reduction in FXR expression in the liver of rats made obese by exposure to a high‐fat diet and with no change in FXR expression in the liver of obese mice exposed to a high fat diet ; in the latter experiments FXR expression was reduced during weight loss when switching to a low fat diet. Several reasons could explain these differences between the human and rodent data (e.g.…”

Section: Discussionmentioning

confidence: 91%

Farnesoid X receptor ‐ a molecular predictor of weight loss after vertical sleeve gastrectomy?

Scott

Elahi

Adebibe

et al. 2019

Obesity Science & Practice

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Summary Objective To determine the expression of the bile acid receptor, farnesoid X (FXR), in human gastric mucosa and investigate correlations between expression and body‐mass index (BMI) and in patients with obesity, with changes in weight and BMI following vertical sleeve gastrectomy (VSG). Methods Human gastric mucosa was obtained from normal/overweight individuals (macroscopically‐normal tissue following surgery for malignancy) or from patients with obesity (VSG). The expression of FXR and its isoforms (FXRα, FXRβ) were examined by quantitative PCR and compared with the G protein‐coupled bile acid receptor, GPBA. In patients with obesity, changes in BMI and weight loss were determined following VSG. Results FXRα was the predominant isoform in normal/overweight individuals. FXR expression was higher in patients with obesity but GPBA receptor expression was unchanged. For those with obesity ( n = 19), no correlation was found between FXR expression and change in Body‐Mass Index (BMI)/month or weight loss/month, taken 3 ± 1 months after surgery, or in BMI or weight at surgery. Conclusions Obesity is associated with increased FXR expression in the gastric mucosa. The findings are preliminary but suggest that this increase in FXR expression is a consequence of obesity, rather than its cause.

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“…However, the TBA level was reduced in the liver of HFD-fed Bsep +/mice, compared with the other mice. An HFD increases the fecal bile acid concentration [36,37] and reduces the hepatic TBA concentration [38]. Indeed, the TBA level was reduced in HFD-fed mice, compared with ND-fed mice (Fig 2A).…”

Section: Plos Onementioning

confidence: 91%

Heterozygous knockout of Bile salt export pump ameliorates liver steatosis in mice fed a high-fat diet

et al. 2020

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The incidence of nonalcoholic steatohepatitis (NASH) is increasing worldwide, including in Asian countries. We reported that the hepatic expression of bile salt export pump (BSEP) was downregulated in patients with NASH, suggesting that BSEP is involved in the pathogenesis of NASH. To identify the underlying mechanism, we analyzed Bsep heterozygous knockout (Bsep +/mice) and wild-type (WT) C57BL/6J mice fed a high-fat diet (HFD) (32.0% animal fat) or normal diet. We examined histological changes, levels of hepatic lipids and hepatic bile acids, and expression of genes related to bile acid and cholesterol metabolism. HFD-fed Bsep +/mice exhibited milder hepatic steatosis and less weight gain, compared to HFD-fed WT mice. The concentrations of total bile acid, triglycerides, and cholesterols were reduced in the liver of HFD-fed Bsep +/mice. Regarding hepatic bile acid metabolism, the expression levels of Farnesoid X receptor (Fxr) and Multidrug resistanceassociated protein 2 were significantly upregulated in HFD-fed Bsep +/mice, compared to HFD-fed WT mice. Furthermore, several alterations were observed in upstream cholesterol metabolism in the liver. The expression levels of bile acid metabolism-related genes were also altered in the intestine of HFD-fed Bsep +/mice. In conclusion, HFD-fed Bsep +/mice exhibited significant alterations of the expression levels of genes related to bile acid and lipid metabolism in both the liver and ileum, resulting in alleviated steatosis and less weight gain. These results suggest the importance of BSEP for maintenance of bile acid and cholesterol metabolism. Further investigations of the involvement of BSEP in the pathogenesis of NASH will provide greater insight and facilitate the development of novel therapeutic modalities.

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Diet-induced obesity and weight loss alter bile acid concentrations and bile acid–sensitive gene expression in insulin target tissues of C57BL/6J mice

Cited by 47 publications

References 42 publications

High fat diet significantly changed the global gene expression profile involved in hepatic drug metabolism and pharmacokinetic system in mice

High fat diet significantly changed the global gene expression profile involved in hepatic drug metabolism and pharmacokinetic system in mice

Farnesoid X receptor ‐ a molecular predictor of weight loss after vertical sleeve gastrectomy?

Heterozygous knockout of Bile salt export pump ameliorates liver steatosis in mice fed a high-fat diet

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