bims-liverm 2023-08-27 papers

Issue of 2023‒08‒27
four papers selected by
Marti Cadena Sandoval, Columbia University

Microorganisms. 2023 Aug 11. pii: 2059. [Epub ahead of print]11(8):

The Crosstalk between Gut Microbiota and Bile Acids Promotes the Development of Non-Alcoholic Fatty Liver Disease.

Zhonglin Li, Hang Yuan, Huikuan Chu, Ling Yang.

Recently the roles of gut microbiota are highly regarded in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The intestinal bacteria regulate the metabolism of bile acids depending on bile salt hydrolase (BSH), 7-dehydroxylation, hydroxysteroid dehydrogenase (HSDH), or amide conjugation reaction, thus exerting effects on NAFLD development through bile acid receptors such as farnesoid X receptor (FXR), Takeda G-protein-coupled bile acid protein 5 (TGR5), and vitamin D receptor (VDR), which modulate nutrient metabolism and insulin sensitivity via interacting with downstream molecules. Reversely, the composition of gut microbiota is also affected by the level of bile acids in turn. We summarize the mutual regulation between the specific bacteria and bile acids in NAFLD and the latest clinical research based on microbiota and bile acids, which facilitate the development of novel treatment modalities in NAFLD.

Keywords: NAFLD; NAFLD treatment; bile acid; bile acid receptor; gut microbiota

DOI: https://doi.org/10.3390/microorganisms11082059

Biology (Basel). 2023 Aug 09. pii: 1105. [Epub ahead of print]12(8):

Dimethyl Sulfoxide Inhibits Bile Acid Synthesis in Healthy Mice but Does Not Protect Mice from Bile-Acid-Induced Liver Damage.

Xi Chen, Huiqiao Li, Yu'e Liu, Jing Qi, Bingning Dong, Shixia Huang, Shangang Zhao, Yi Zhu.

Bile acids serve a vital function in lipid digestion and absorption; however, their accumulation can precipitate liver damage. In our study, we probed the effects of dimethyl sulfoxide (DMSO) on bile acid synthesis and the ensuing liver damage in mice induced by bile acids. Our findings indicate that DMSO efficaciously curbs bile acid synthesis by inhibiting key enzymes involved in the biosynthetic pathway, both in cultured primary hepatocytes and in vivo. Contrarily, we observed that DMSO treatment did not confer protection against bile-acid-induced liver damage in two distinct mouse models: one induced by a 0.1% DDC diet, leading to bile duct obstruction, and another induced by a CDA-HFD, resulting in non-alcoholic steatohepatitis (NASH). Histopathological and biochemical analyses unveiled a comparable extent of liver injury and fibrosis levels in DMSO-treated mice, characterized by similar levels of increase in Col1a1 and Acta2 expression and equivalent total liver collagen levels. These results suggest that, while DMSO can promptly inhibit bile acid synthesis in healthy mice, compensatory mechanisms might rapidly override this effect, negating any protective impact against bile-acid-induced liver damage in mice. Through these findings, our study underscores the need to reconsider treating DMSO as a mere inert solvent and prompts further exploration to identify more effective therapeutic strategies for the prevention and treatment of bile-acid-associated liver diseases.

Keywords: bile acid; dimethyl sulfoxide (DMSO); liver damage; nonalcoholic steatohepatitis (NASH)

DOI: https://doi.org/10.3390/biology12081105

Clin Exp Gastroenterol. 2023 ;16 137-146

Relationship of Serum Bile Acids with Fat Deposition in the Pancreas, Liver, and Skeletal Muscle.

Zena Al-Ani, Juyeon Ko, Maxim S Petrov.

Introduction: Ectopic fat deposition is well appreciated as a key contributor to digestive and liver diseases. Bile acids have emerged as pleiotropic signalling molecules involved in numerous metabolic pathways. The aim was to study the associations of bile acids with ectopic fat deposition and lipid panel.Methods: A single 3.0 Tesla magnetic resonance imaging scanner was employed to measure fat deposition in the pancreas, liver, and skeletal muscle in 76 adults. Blood samples were drawn to determine total bile acids and lipid panel. Linear regression analyses were run, taking into account age, sex, body mass index, and other covariates.
Results: The studied ectopic fat depots were not significantly associated with levels of total bile acids in serum. Total bile acids were significantly associated high-density lipoprotein cholesterol - consistently in both the unadjusted (p = 0.018) and all adjusted models (p = 0.012 in the most adjusted model). Low-density lipoprotein cholesterol, total cholesterol, and triglycerides were not significantly associated with total bile acids in both the unadjusted and all adjusted models.
Conclusion: Fat deposition in the pancreas, liver, and skeletal muscle is not associated with circulating levels of total bile acids. High-density lipoprotein cholesterol is the only component of lipid panel that is associated with total bile acids.

Keywords: bile acids; cholesterol; intra-hepatic fat; intra-pancreatic fat; skeletal muscle fat; triglycerides

DOI: https://doi.org/10.2147/CEG.S422995

Hepatobiliary Pancreat Dis Int. 2023 Aug 12. pii: S1499-3872(23)00128-5. [Epub ahead of print]

In vivo mouse models to study bile acid synthesis and signaling.

Anisha Bhattacharya, Rulaiha E Taylor, Grace L Guo.

The synthesis of bile acids (BAs) is carried out by complex pathways characterized by sequential chemical reactions in the liver through various cytochromes P450 (CYP) and other enzymes. Maintaining the integrity of these pathways is crucial for normal physiological function in mammals, encompassing hepatic and neurological processes. Studying on the deficiencies in BA synthesis genes offers valuable insights into the significance of BAs in modulating farnesoid X receptor (FXR) signaling and metabolic homeostasis. By creating mouse knockout (KO) models, researchers can manipulate deficiencies in genes involved in BA synthesis, which can be used to study human diseases with BA dysregulation. These KO mouse models allow for a more profound understanding of the functions and regulations of genes responsible for BA synthesis. Furthermore, KO mouse models shed light on the distinct characteristics of individual BA and their roles in nuclear receptor signaling. Notably, alterations of BA synthesis genes in mouse models have distinct differences when compared to human diseases caused by the same BA synthesis gene deficiencies. This review summarizes several mouse KO models used to study BA synthesis and related human diseases, including mice deficient in Cyp7a1, Cyp27a1, Cyp7a1/Cyp27a1, Cyp8b1, Cyp7b1, Cyp2c70, Cyp2a12, and Cyp2c70/Cyp2a12, as well as germ-free mice.

Keywords: Bile acid; Farnesoid X receptor; Liver diseases; Species difference

DOI: https://doi.org/10.1016/j.hbpd.2023.08.009