Effects of Sleeve Gastrectomy on Serum 12α-Hydroxylated Bile Acids in a Diabetic Rat Model

Wang, Minggang; Wu, Qunzheng; Xie, Haibin; Shao, Yi; Zhong, Maiying; Zhang, Xiang; Liu, Shaozhuang; He, Xiao; Hu, Sanyuan

doi:10.1007/s11695-017-2714-6

Cited by 9 publications

(9 citation statements)

References 34 publications

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“…Recent studies have confirmed that MAFG is a target of FXR and a key transcriptional repressor of bile acid synthesis and metabolism [8–11]. MAFG has been shown to reduce the transcription level of CYP8B1 in the liver [12].…”

Section: Introductionmentioning

confidence: 99%

A Possible Mechanism of Metformin in Improving Insulin Resistance in Diabetic Rat Models

et al. 2019

International Journal of Endocrinology

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Background Type 2 diabetes has become one of the most common diseases worldwide, causing a serious social burden. As a first-line treatment for diabetes, metformin can effectively improve insulin resistance. It has been reported that 12α-hydroxylated BA (mainly CA) is associated with insulin resistance. The purpose of this study was to analyze the changes in CA and possible signaling mechanisms in diabetic rats after metformin intervention. Methods HepG2 cells were cultured after adding different concentrations of metformin. The cell viability was measured using CCK8 kit, and the expression of FXR, MAFG, and CYP8B1 in cells was detected by WB. The rat models of type 2 diabetes were induced by low-dose streptozotocin by feeding a high-fat diet, and the control rats (CON) were fed on normal food; the diabetic rats (DM) were given a high-fat diet without supplementation with metformin, while the metformin-treated diabetic rats (DM + MET) were given a high-fat diet and supplemented with metformin. Biochemical parameters were detected at the end of the test. Expression levels of FXR, CYP8B1, and MAFG were assessed by WB. Serum CA were measured using an enzyme-linked immunosorbent assay (ELISA). Results In HepG2 cells, metformin dose-dependently enhanced the transcriptional activity of FXR and MAFG and inhibited the expression of CYP8B1. Metformin-treated DM rats showed improved glucose and bile acid metabolism. In addition, significantly increased FXR and MAFG and decreased CYP8B1 were observed in DM + MET rats. At the same time, the CA content of metformin-treated rats was lower than that of diabetic rats. Conclusion Changes in CA synthesis after metformin treatment may be associated with inhibition of CYP8B1. These results may play an important role in improving insulin sensitivity after metformin treatment.

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Section: Introductionmentioning

confidence: 99%

A Possible Mechanism of Metformin in Improving Insulin Resistance in Diabetic Rat Models

et al. 2019

International Journal of Endocrinology

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“…Serum BA levels were higher in obese patients who received RYGB when compared to controls (no RYGB), and elevated levels of BAs were sustained for at least 2 years post-surgery (Nakatani et al, 2009;Patti et al, 2009). Further investigation demonstrated that the mechanism is due to the regulation of specific BAs (Wang et al, 2017;Browning et al, 2019). This might also be explained by the evidence that plasma BAs were negatively correlated with cognitive restraint of eating (Prinz et al, 2015).…”

Section: Obesitymentioning

confidence: 93%

“…Genetic ablation of Cyp8b1 decreases BA profile hydrophobicity and protects against several metabolic diseases, including obesity and T2D, in mice (Zaborska and Cummings, 2018). Of note, the percentage of 12α-hydroxylated BAs was reduced after SG, associated with overexpression of V-Maf avian musculoaponeurotic fibrosarcoma oncogene homolog G (MAFG) and lower mRNA and protein levels of CYP8B1 (Wang et al, 2017). Interestingly, MAFG is an FXR target gene that transcriptionally represses CYP8B1 expression (de Aguiar Vallim et al, 2015); these results suggest that in addition to FXR and TGR5, the downstream CYP8B1 may present an alternative target for bariatric surgery.…”

Section: Bariatric Surgeriesmentioning

confidence: 99%

Bile-ology: from bench to bedside

Jin

Fang

Fan

et al. 2019

J. Zhejiang Univ. Sci. B

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Bile acids (BAs) are originally known as detergents essential for the digestion and absorption of lipids. In recent years, extensive research has unveiled new functions of BAs as gut hormones that modulate physiological and pathological processes, including glucose and lipid metabolism, energy expenditure, inflammation, tumorigenesis, cardiovascular disease, and even the central nervous system in addition to cholesterol homeostasis, enterohepatic protection and liver regeneration. BAs are closely linked with gut microbiota which might explain some of their crucial roles in organs. The signaling actions of BAs can also be mediated through specific nuclear receptors and membranebound G protein-coupled receptors. Several pharmacological agents or bariatric surgeries have demonstrated efficacious therapeutic effects on metabolic diseases through targeting BA signaling. In this mini-review, we summarize recent advances in bile-ology, focusing on its translational studies.

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“…However, BA includes more than 20 components, each of which may have specific effects on metabolism (de Aguiar Vallim et al, 2013). Notably, 12α-hydroxylated bile acids promote liver fibrosis through TGR5mediated p38MAPK and ERK1/2 signaling, but these bile acids were significantly reduced after SG (Wang et al, 2017;Xie et al, 2021). RYGB upregulates the expression of hepatic BA targets FXR and peroxisome proliferator-activated receptor-α (PPARα) in severely obese patients, and these changes are accompanied by regression of NASH and T2DM after 1 year (Francque et al, 2015;Mazzini et al, 2019).…”

Section: Changes In Bile Acid Metabolism Transport and Signal Transdu...mentioning

confidence: 99%

Bariatric surgery for diabetic comorbidities: A focus on hepatic, cardiac and renal fibrosis

Ding

Zhang

et al. 2022

Front. Pharmacol.

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Effects of Sleeve Gastrectomy on Serum 12α-Hydroxylated Bile Acids in a Diabetic Rat Model

Abstract: The percentage of 12α-hydroxylated bile acids was reduced after SG, which was relevant with the inhibition of CYP8B1 and overexpression of MAFG. These outcomes may play an important role in the improvement of insulin sensitivity following SG.

Cited by 9 publications

References 34 publications

A Possible Mechanism of Metformin in Improving Insulin Resistance in Diabetic Rat Models

A Possible Mechanism of Metformin in Improving Insulin Resistance in Diabetic Rat Models

Bile-ology: from bench to bedside

Bariatric surgery for diabetic comorbidities: A focus on hepatic, cardiac and renal fibrosis

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