Farnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis

Jiao, Yang; Lu, Yan; Li, Xiaoying

doi:10.1038/aps.2014.116

Cited by 156 publications

(139 citation statements)

References 68 publications

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“…BA activation of TGR5 results in increased secretion of GLP-1 and decreased insulin resistance in obese mice (Thomas et al, 2009). FXR decreases hepatic gluconeogenesis, glycolysis, and increases glycogen synthesis (Jiao et al, 2015). Type II diabetes is associated with increased gluconeogenesis and, therefore, BAs, via FXR, may play a role in the development of medications to combat type II diabetes.…”

Section: Bas and Glucose Cholesterol And Lipid Metabolism Pathwaysmentioning

confidence: 99%

The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Chow

Lee

Guo

2017

Molecular Aspects of Medicine

119

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Nonalcoholic fatty liver disease is growing in prevalence worldwide. It is started by the presence of macrosteatosis on liver histology but is often clinically asymptomatic. However, it can progress into nonalcoholic steatohepatitis which is a more severe form of liver disease characterized by inflammation and fibrosis. Further progression leads to cirrhosis, which predisposes patients to hepatocellular carcinoma or liver failure. The mechanism by which simple steatosis progresses to steatohepatitis is not entirely clear. However, multiple pathways have been proposed. A common link amongst many of these pathways is disruption of the homeostasis of bile acids. Other than aiding in the absorption of lipids and lipid-soluble vitamins, bile acids act as ligands. For example, they bind to farnesoid X receptor, which is critically involved in many of the pathways responsible for maintaining bile acid, glucose, and lipid homeostasis. Alterations to these pathways can lead to deregulation in energy balance and increased inflammation and fibrosis. Repeated insults over time may be the key to development of steatohepatitis. For this reason, current drugs target aspects of these pathways to try to reduce and halt inflammation and fibrosis. This review will focus on the role of bile acids in these various pathways and how changes in these pathways may result in steatohepatitis. While there is no approved pharmaceutical treatment for either hepatic steatosis or steatohepatitis, this review will also touch upon the multitude of potential therapies.

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Section: Bas and Glucose Cholesterol And Lipid Metabolism Pathwaysmentioning

confidence: 99%

The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Chow

Lee

Guo

2017

Molecular Aspects of Medicine

119

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“…Bile acids play significant roles in lipid and glucose homeostasis (Cariou and Staels, 2007; Jiao et al, 2015; Ma et al, 2006a; Sinal et al, 2000; Y. Zhang et al, 2006) and regulation of energy expenditure (Thomas et al, 2009; Watanabe et al, 2006).…”

Section: Bile Acidsmentioning

confidence: 99%

“…Zhang et al, 2006) and regulation of energy expenditure (Thomas et al, 2009; Watanabe et al, 2006). These metabolic effects have been linked to the primary bile acid receptor FXR (Claudel et al, 2005; Jiao et al, 2015; Pang et al, 2015; Tu et al, 2000). FXR regulates bile acid synthesis (Fu et al, 2015) by modulating CYP7A1, but FXR also directly influences glucose and lipid metabolism (Cariou et al, 2005; Duran-Sandoval et al, 2005; Sinal et al, 2000; van Dijk et al, 2009; Watanabe et al, 2004).…”

Section: Bile Acidsmentioning

confidence: 99%

Bile acids and bariatric surgery

Albaugh

Banan

Ajouz

et al. 2017

Molecular Aspects of Medicine

111

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Bariatric surgery, specifically Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), are the most effective and durable treatments for morbid obesity and potentially a viable treatment for type 2 diabetes (T2D). The resolution rate of T2D following these procedures is between 40-80% and far surpasses that achieved by medical management alone. The molecular basis for this improvement is not entirely understood, but has been attributed in part to the altered enterohepatic circulation of bile acids. In this review we highlight how bile acids potentially contribute to improved lipid and glucose homeostasis, insulin sensitivity and energy expenditure after these procedures. The impact of altered bile acid levels in enterohepatic circulation is also associated with changes in gut microflora, which may further contribute to some of these beneficial effects. We highlight the beneficial effects of experimental surgical procedures in rodents that alter bile secretory flow without gastric restriction or altering nutrient flow. This information suggests a role for bile acids beyond dietary fat emulsification in altering whole body glucose and lipid metabolism strongly, and also suggests emerging roles for the activation of the bile acid receptors farnesoid x receptor (FXR) and G-protein coupled bile acid receptor (TGR5) in these improvements. The limitations of rodent studies and the current state of our understanding is reviewed and the potential effects of bile acids mediating the short-and long-term metabolic improvements after bariatric surgery is critically examined.

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“…In this special issue, we will focus on the emerging roles of orphan nuclear receptors in metabolism. Jiao and coworkers review the regulatory role of FXR in homeostasis of hepatic triglyceride [5] . Audet-wash and Giguère review the roles of estrogen-related receptor α and γ in metabolic control and related diseases [6] .…”

Section: Editorialmentioning

confidence: 99%

Family reunion of nuclear hormone receptors: structures, diseases, and drug discovery

2015

Acta Pharmacol Sin

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EditorialHormones comprise one of the most effective classes of messengers that transmit cell to cell communication in eukaryotic systems. Cells receive messages of hormones through protein receptors, and then translate the hormone signals into concrete action of physiological responses. Homeostasis of hormone systems is essential for human health, and aberrant regulation of hormone signaling has been associated with many diseases, including cancer, diabetes, and inflammation diseases. As such, targeting hormone signaling pathways has become a major venue of pharmacological intervention of many health abnormalities. There are two major classes of hormone receptors: G-protein coupled receptors and nuclear hormone receptors, both of which consist of the top two classes of the most successful drug targets. Two years ago, we published a special issue on structures, biology and drug discovery of G-protein coupled receptors, which has been well received by drug discovery research communities. This year marked the 30th anniversary of the cloning of the first member of the nuclear receptor family and 25th year of the discovery of orphan nuclear receptors, for which no cognate ligands were known at the time of their cloning. Since then we have witnessed a tremendous expansion of our knowledge of this family of receptors. In this special issue, we collected eleven exciting review articles, highlighting our current understanding of structure, function, disease relevance, and drug discovery of nuclear receptors.Hormones androgen and estrogen have long been known to play key roles in development, growth, and homeostasis of reproductive systems and their dysregulation is the major cause of prostate cancer and breast cancer. The first article by Tan and coworkers will provide comprehensive review on structures, diseases relevance and drug discovery of androgen receptor, the oncogenic driver of prostate cancer [1] . The second review article by Ikeda and coworkers covers the roles of estrogen-responsive genes in breast cancer [2] . Beside androgen receptor and estrogen receptor, the two of classical steroid hormone receptors in cancers, orphan nuclear receptors COUPTFs also known to play important role in tumorigenesis, and they are respectively reviewed by Xu and coworkers [3] . In addition, the roles of bile acid receptor FXR in liver cancer will be reviewed by Huang and coworkers [4] . Nuclear hormone receptors are also well known for their central roles in metabolic regulation. Classic examples are peroxisome proliferator activated receptors (PPARs) and receptors for glucocorticoids and thyroid hormone, for which roles have been well reviewed in the literatures. In this special issue, we will focus on the emerging roles of orphan nuclear receptors in metabolism. Jiao and coworkers review the regulatory role of FXR in homeostasis of hepatic triglyceride [5] . Audet-wash and Giguère review the roles of estrogen-related receptor α and γ in metabolic control and related diseases [6] . Yan and Xie review the role of constitutive...

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Farnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis

Cited by 156 publications

References 68 publications

The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Bile acids and bariatric surgery

Family reunion of nuclear hormone receptors: structures, diseases, and drug discovery

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