Bile acids as regulatory molecules and potential targets in metabolic diseases

Xie, Ai-jin; Mai, Chu-Tian; Zhu, Yi‐Zhun; Liu, Xiancheng; Xie, Ying

doi:10.1016/j.lfs.2021.120152

Cited by 25 publications

(22 citation statements)

References 170 publications

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“…Under the action of intestinal microbiota, primary BAs form secondary BAs, including deoxycholic acid (DCA) from CA and lithocholic acid (LCA) and ursodeoxycholic acid (UDCA) from CDCA (A. Xie et al, 2021a ). The synthesis of BA is dominated by the classical pathway, forming primary BA (12α-OH BA) that is hydroxylated at the carbon 12 position, while the alternative pathway synthesizes non-12α-OH BA.…”

Section: Ba Metabolism and Regulation In Humans And Micementioning

confidence: 99%

The role of bile acid metabolism in the occurrence and development of NAFLD

Bing

2022

Front. Mol. Biosci.

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Non-alcoholic fatty liver disease (NAFLD) has become one of the important causes of cirrhosis and liver cancer, resulting in a huge medical burden worldwide. Currently, effective non-invasive diagnostic indicators and drugs for NAFLD are still lacking. With the development of metabolomics technology, the changes in metabolites during the development of NAFLD have been gradually revealed. Bile acid (BA) is the main endpoint of cholesterol metabolism in the body. In addition, it also acts as a signaling factor to regulate metabolism and inflammation in the body through the farnesyl X receptor and G protein-coupled BA receptor. Studies have shown that BA metabolism is associated with the development of NAFLD, but a large number of animal and clinical studies are still needed. BA homeostasis is maintained through multiple negative feedback loops and the enterohepatic circulation of BA. Recently, treatment of NAFLD by interfering with BA synthesis and metabolism has become a new research direction. Here, we review the changes in BA metabolism and its regulatory mechanisms during the development of NAFLD and describe the potential of studies exploring novel non-invasive diagnostic indicators and therapeutic targets for NAFLD based on BA metabolism.

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Section: Ba Metabolism and Regulation In Humans And Micementioning

confidence: 99%

The role of bile acid metabolism in the occurrence and development of NAFLD

Bing

2022

Front. Mol. Biosci.

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“…For instance, 16(R)-HETE can suppress the activation of polymorphonuclear leukocytes and reduce intracranial pressure ( 53 ). Chenodeoxycholic acid, which is involved in primary bile acid biosynthesis, inhibits pro-inflammatory cytokines ( 56 ). These suggested that OKG regulates immune status and alleviates the suppression in piglets infected by ETEC via stimulating the ileal mucosa microbe and metabolites.…”

Section: Discussionmentioning

confidence: 99%

Ornithine α-Ketoglutarate Alleviates Inflammation via Regulating Ileal Mucosa Microbiota and Metabolites in Enterotoxigenic Escherichia coli-Infected Pigs

Bao

Yang

et al. 2022

Front. Nutr.

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Enterotoxigenic Escherichia coli (ETEC) is one of the main causes of diarrhea in weaned piglets, and ornithine α-ketoglutarate (OKG) as a food supplement has been shown to improve intestinal immune status in animals and humans. However, it remains unknown whether OKG alleviates inflammation through the regulation of gut microbiota and its metabolites on ETEC-infected piglets. This study was conducted to explore the impact of OKG on growth performance, immunity, and ileal mucosa microbiota and its metabolites in piglets infected with ETEC. On a total of 40 pigs, a 2 × 2 factor design was performed; the major factors were diet (basal diet or 1% OKG diet) and challenge (E. coli or LB Broth). The results showed that ETEC-infection inhibited growth performance, and OKG supplementation alleviated growth performance. Interestingly, ETEC-infection increased the serum TNF-α and IL-6, decreased the serum IL-10, downregulated the mRNA expression of IL-1β, IL-6, MyD88, and improved the mRNA expression of IL-8, IL-18, and TLR4. OKG inhibited serum IL-6, suppressed the phosphorylation of downstream signals of NF-κB/JNK in the ileum, and enhanced serum IL-10 and ileum SIgA in ETEC-challenged piglets. OKG supplementation enhanced the mRNA expression of IL-1β and IL-10 and reduced NF-κB and MyD88 in the ileum. Importantly, OKG reversed intestinal microbiota dysfunction, including the diversity of ileal microbiota, the relative abundances of Actinobacillus, Turicibacter, and [Acetivibrio]_ethanolgignens_group, which significantly affected arachidonic acid metabolism and primary bile acid biosynthesis. Collectively, our results suggest that OKG improves growth performance, regulates immunity, and ileal mucosa microbiota and its metabolites in ETEC-infected piglets.

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“…The pathogenesis of depression, AD, stroke, and other neurological diseases is closely related to apoptosis [109–111]. A variety of BAs, such as UDCA, TCA, GCDCA, TUDCA, have been found to mediate apoptosis in neuronal cells [112–114].…”

Section: Mechanistic Roles and Treatment Of Bile Acids In Neurologica...mentioning

confidence: 99%

“…diseases is closely related to apoptosis[109][110][111]. A variety of BAs, such as UDCA, TCA, GCDCA, TUDCA, have been found to mediate apoptosis in neuronal cells[112][113][114].…”

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confidence: 99%

The clinical and mechanistic roles of bile acids in depression, Alzheimer's disease, and stroke

Lirong

Zhao

et al. 2022

Proteomics

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The burden of neurological and neuropsychiatric disorders continues to grow with significant impacts on human health and social economy worldwide. Increasing clinical and preclinical evidences have implicated that bile acids (BAs) are involved in the onset and progression of neurological and neuropsychiatric diseases. Here, we summarized recent studies of BAs in three types of highly prevalent brain disorders, depression, Alzheimer's disease, and stroke. The shared and specific BA profiles were explored and potential markers associated with disease development and progression were summarized. The mechanistic roles of BAs were reviewed with focuses on inflammation, gut-brain-microbiota axis, cellular apoptosis. We also discussed future perspectives for the prevention and treatment of neurological and neuropsychiatric disorders by targeting BAs and related molecules and gut microbiota. Our understanding of BAs and their roles in brain disorders is still evolving. A large number of questions still need to be addressed on the emerging crosstalk among central, peripheral, intestine, and their contribution to brain and mental health.

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Bile acids as regulatory molecules and potential targets in metabolic diseases

Cited by 25 publications

References 170 publications

The role of bile acid metabolism in the occurrence and development of NAFLD

The role of bile acid metabolism in the occurrence and development of NAFLD

Ornithine α-Ketoglutarate Alleviates Inflammation via Regulating Ileal Mucosa Microbiota and Metabolites in Enterotoxigenic Escherichia coli-Infected Pigs

The clinical and mechanistic roles of bile acids in depression, Alzheimer's disease, and stroke

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