Knockout of farnesoid X receptor aggravates process of diabetic cardiomyopathy

Qiang, Sujing; Tao, Lingyun; Zhou, Jie; Wang, Qianwan; Wang, Kesheng; Lü, Meiling; Wang, Weifeng; Lin, Han Chieh; Xue, Sheng; Chen, Yan; Zhu, Huanhuan; Liu, Zheng; Zhang, Yue

doi:10.1016/j.diabres.2020.108033

Cited by 10 publications

(4 citation statements)

References 33 publications

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“…Also, the absence of FXR expression affected cardiac function and elevated the levels of myocardial injury markers associated with a BA overload [ 35 ]. Similarly, in a diabetes mice model, the FXR knock-out aggravates cardiac fibrosis and lipid accumulation [ 36 ]. Furthermore, FXR agonists diminish cardiac fibrosis, kidney damage, and pancreatic hypertrophy and reduce lipid serum levels in obese/diabetic mice models, decreasing hepatic fibrosis and portal pressure in a nonalcoholic steatohepatitis rat model [ 37 – 39 ].…”

Section: Bile Acid Receptorsmentioning

confidence: 99%

Redox‐Dependent Effects in the Physiopathological Role of Bile Acids

Orozco-Aguilar

Simón

Cabello-Verrugio

2021

Oxidative Medicine and Cellular Longevity

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Bile acids (BA) are recognized by their role in nutrient absorption. However, there is growing evidence that BA also have endocrine and metabolic functions. Besides, the steroidal-derived structure gives BA a toxic potential over the biological membrane. Thus, cholestatic disorders, characterized by elevated BA on the liver and serum, are a significant cause of liver transplant and extrahepatic complications, such as skeletal muscle, central nervous system (CNS), heart, and placenta. Further, the BA have an essential role in cellular damage, mediating processes such as membrane disruption, mitochondrial dysfunction, and the generation of reactive oxygen species (ROS) and oxidative stress. The purpose of this review is to describe the BA and their role on hepatic and extrahepatic complications in cholestatic diseases, focusing on the association between BA and the generation of oxidative stress that mediates tissue damage.

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Section: Bile Acid Receptorsmentioning

confidence: 99%

Redox‐Dependent Effects in the Physiopathological Role of Bile Acids

Orozco-Aguilar

Simón

Cabello-Verrugio

2021

Oxidative Medicine and Cellular Longevity

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“…Recently, several studies reported that overexpression of FXR in the kidney substantially alleviated hypertension and elevated renal nitric oxide (NO) levels, which was achieved by stimulating the expression of endothelial nitric oxide synthase (eNOS) in a mouse model of hypertension induced by an 8week regimen of 20% fructose in drinking water combined with a 4% sodium chloride diet (referred to as HFS) (Ghebremariam et al, 2013;Li et al, 2015). In the kidney, activation of FXR attenuated acute kidney injury caused by cisplatin and renal ischemia-reperfusion (I/R) through regulating apoptosis, ferroptosis, and autophagy (Bae et al, 2014;Gai et al, 2017;Luan et al, 2021;Zhang et al, 2022). Additionally, FXR agonists also improved renal inflammation, fibrosis, lipid accumulation, and glucose metabolism disorders, which prevented the progression of chronic kidney disease (Evans et al, 2009;Wang et al, 2010;Zhou et al, 2016;Marquardt et al, 2017).…”

Section: Classification and General Function Of Bile Acid Receptorsmentioning

confidence: 99%

Bile acid receptors and renal regulation of water homeostasis

Guo,

Luo,

Xie

et al. 2023

Front. Physiol.

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The kidney is the key organ responsible for maintaining the body’s water and electrolyte homeostasis. About 99% of the primary urine filtered from the Bowman’s capsule is reabsorbed along various renal tubules every day, with only 1–2 L of urine excreted. Aquaporins (AQPs) play a vital role in water reabsorption in the kidney. Currently, a variety of molecules are found to be involved in the process of urine concentration by regulating the expression or activity of AQPs, such as antidiuretic hormone, renin-angiotensin-aldosterone system (RAAS), prostaglandin, and several nuclear receptors. As the main bile acid receptors, farnesoid X receptor (FXR) and membrane G protein-coupled bile acid receptor 1 (TGR5) play important roles in bile acid, glucose, lipid, and energy metabolism. In the kidney, FXR and TGR5 exhibit broad expression across all segments of renal tubules, and their activation holds significant therapeutic potential for numerous acute and chronic kidney diseases through alleviating renal lipid accumulation, inflammation, oxidative stress, and fibrosis. Emerging evidence has demonstrated that the genetic deletion of FXR or TGR5 exhibits increased basal urine output, suggesting that bile acid receptors play a critical role in urine concentration. Here, we briefly summarize the function of bile acid receptors in renal water reabsorption and urine concentration.

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“…Therefore, it is speculated that FXR signaling is involved in several cardiac diseases associated with cardiomyocyte growth and apoptosis. FXR also regulates cardiac lipid accumulation in obese and diabetic patients by inducing the expression of β-oxidative genes in cardiomyocytes [67,68]. As an agonist of FXR, GW4064 can significantly improve insulin resistance and cardiomyocyte disorders [69].…”

Section: Bile Acid Metabolism In Cardiomyocytesmentioning

confidence: 99%

The Role of Bile Acids in Cardiovascular Diseases: from Mechanisms to Clinical Implications

Zhang¹,

Zhou²,

Wu³

et al. 2022

Aging and disease

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Bile acids (BAs), key regulators in the metabolic network, are not only involved in lipid digestion and absorption but also serve as potential therapeutic targets for metabolic disorders. Studies have shown that cardiac dysfunction is associated with abnormal BA metabolic pathways. As ligands for several nuclear receptors and membrane receptors, BAs systematically regulate the homeostasis of metabolism and participate in cardiovascular diseases (CVDs), such as myocardial infarction, diabetic cardiomyopathy, atherosclerosis, arrhythmia, and heart failure. However, the molecular mechanism by which BAs trigger CVDs remains controversial. Therefore, the regulation of BA signal transduction by modulating the synthesis and composition of BAs is an interesting and novel direction for potential therapies for CVDs. Here, we mainly summarized the metabolism of BAs and their role in cardiomyocytes and noncardiomyocytes in CVDs. Moreover, we comprehensively discussed the clinical prospects of BAs in CVDs and analyzed the clinical diagnostic and application value of BAs. The latest development prospects of BAs in the field of new drug development are also prospected. We aimed to elucidate the underlying mechanism of BAs treatment in CVDs, and the relationship between BAs and CVDs may provide new avenues for the prevention and treatment of these diseases.

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Knockout of farnesoid X receptor aggravates process of diabetic cardiomyopathy

Cited by 10 publications

References 33 publications

Redox‐Dependent Effects in the Physiopathological Role of Bile Acids

Redox‐Dependent Effects in the Physiopathological Role of Bile Acids

Bile acid receptors and renal regulation of water homeostasis

The Role of Bile Acids in Cardiovascular Diseases: from Mechanisms to Clinical Implications

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