scholarly journals Bile Acids, FXR, and Metabolic Effects of Bariatric Surgery

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Olivier F. Noel ◽  
Christopher D. Still ◽  
George Argyropoulos ◽  
Michael Edwards ◽  
Glenn S. Gerhard
Keyword(s):  
Bariatric Surgery ◽  
Lipid Metabolism ◽  
Bile Acids ◽  
Metabolic Diseases ◽  
Overweight And Obesity ◽  
Farnesoid X Receptor ◽  
Metabolic Effects ◽  
The Novel ◽  
Treatment Of Obesity ◽  
Lipid Metabolism Genes

Overweight and obesity represent major risk factors for diabetes and related metabolic diseases. Obesity is associated with a chronic and progressive inflammatory response leading to the development of insulin resistance and type 2 diabetes (T2D) mellitus, although the precise mechanism mediating this inflammatory process remains poorly understood. The most effective intervention for the treatment of obesity, bariatric surgery, leads to glucose normalization and remission of T2D. Recent work in both clinical studies and animal models supports bile acids (BAs) as key mediators of these effects. BAs are involved in lipid and glucose homeostasis primarily via the farnesoid X receptor (FXR) transcription factor. BAs are also involved in regulating genes involved in inflammation, obesity, and lipid metabolism. Here, we review the novel role of BAs in bariatric surgery and the intersection between BAs and immune, obesity, weight loss, and lipid metabolism genes.

scholarly journals Effect of ursodeoxycholic acid on lipid metabolism: through the prism of evidence from 2019.

2020 ◽  
Vol 46 (1) ◽  
pp. 83-88
Author(s):  
N. B. Gubergrits ◽  
N.V. Byelyayeva ◽  
T. L. Mozhyna ◽  
G. M. Lukashevich ◽  
P. G. Fomenko
Keyword(s):  
Lipid Metabolism ◽  
Bile Acid ◽  
Bile Acids ◽  
De Novo ◽  
Gallstone Disease ◽  
Farnesoid X Receptor ◽  
Synthesis Rate ◽  
Primary Biliary Cholangitis ◽  
Fractional Synthesis Rate ◽  
Fractional Synthesis

After the discovery of the method of ursodeoxycholic acid’s (UDCA) synthesis and the publication of evidence confirming its ability to reduce the lithogenic properties of bile, active clinical use of UDCA began in the world. This drug, which has pleiotropic effect (choleretic, cytoprotective, immunomodulatory, antiapoptic, litholytic, hypocholesterolemic), has proven its effectiveness in the treatment various diseases: primary biliary cholangitis, intrahepatic cholestasis of pregnancy, gallstone disease. Being a tertiary bile acid, UDCA stimulates bile acid synthesis by reducing the circulating fibroblast growth factor 19 and inhibiting the activation of the farnesoid X-receptor (FXR), which leads to the induction of cholesterol-7α-hydroxylase, a key enzyme in the synthesis of bile acid de novo, mediating the conversion of cholesterol into bile acids. Changes in the formation of bile acids and cholesterol while taking UDCA intake is accompanied by activation of the main enzyme of cholesterol synthesis - 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Under the influence of UDCA the activity of stearoyl-Coa desaturase (SCD) in visceral white adipose tissue increases. According to studies conducted in 2019, UDCA improves lipid metabolism by regulating the activity of the ACT/mTOR signaling pathway, reduces the synthesis of cholesterol, decreases the fractional synthesis rate of cholesterol and the fractional synthesis rate of triglycerides. It has been proved that UDCA is accompanied by a decrease in the level of total cholesterol and low density lipoprotein cholesterol.

scholarly journals Update on FXR Biology: Promising Therapeutic Target?

2018 ◽  
Vol 19 (7) ◽  
pp. 2069 ◽  
Author(s):  
Chang Han
Keyword(s):  
Therapeutic Target ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Farnesoid X Receptor ◽  
Metabolic Effects ◽  
Metabolic Dysfunction ◽  
Energy Status ◽  
Safety Issues ◽  
Attractive Therapeutic Target

Farnesoid X receptor (FXR), a metabolic nuclear receptor, plays critical roles in the maintenance of systemic energy homeostasis and the integrity of many organs, including liver and intestine. It regulates bile acid, lipid, and glucose metabolism, and contributes to inter-organ communication, in particular the enterohepatic signaling pathway, through bile acids and fibroblast growth factor-15/19 (FGF-15/19). The metabolic effects of FXR are also involved in gut microbiota. In addition, FXR has various functions in the kidney, adipose tissue, pancreas, cardiovascular system, and tumorigenesis. Consequently, the deregulation of FXR may lead to abnormalities of specific organs and metabolic dysfunction, allowing the protein as an attractive therapeutic target for the management of liver and/or metabolic diseases. Indeed, many FXR agonists have been being developed and are under pre-clinical and clinical investigations. Although obeticholic acid (OCA) is one of the promising candidates, significant safety issues have remained. The effects of FXR modulation might be multifaceted according to tissue specificity, disease type, and/or energy status, suggesting the careful use of FXR agonists. This review summarizes the current knowledge of systemic FXR biology in various organs and the gut–liver axis, particularly regarding the recent advancement in these fields, and also provides pharmacological aspects of FXR modulation for rational therapeutic strategies and novel drug development.

Bile acids and the metabolic syndrome

2019 ◽  
Vol 56 (3) ◽  
pp. 326-337 ◽  
Author(s):  
Emma Rose McGlone ◽  
Stephen R Bloom
Keyword(s):  
Diabetes Mellitus ◽  
Bile Acid ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Metabolic Effects ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Alcoholic Fatty Liver Disease

Bile acids have important roles in the regulation of lipid, glucose and energy metabolism. Metabolic diseases linked to obesity, including type 2 diabetes mellitus and non-alcoholic fatty liver disease, are associated with dysregulation of bile acid homeostasis. Here, the basic chemistry and regulation of bile acids as well as their metabolic effects will be reviewed. Changes in circulating bile acids associated with obesity and related diseases will be reviewed. Finally, pharmaceutical manipulation of bile acid homeostasis as therapy for metabolic diseases will be outlined.

scholarly journals Metabolic Effects of Bile Acids: Potential Role in Bariatric Surgery

2019 ◽  
Vol 8 (2) ◽  
pp. 235-246 ◽  
Author(s):  
Charles R. Flynn ◽  
Vance L. Albaugh ◽  
Naji N. Abumrad
Keyword(s):  
Bariatric Surgery ◽  
Bile Acids ◽  
Potential Role ◽  
Metabolic Effects

scholarly journals Metabolic Effects of Bariatric Surgery

2018 ◽  
Vol 64 (1) ◽  
pp. 72-81 ◽  
Author(s):  
Piriyah Sinclair ◽  
Neil Docherty ◽  
Carel W le Roux
Keyword(s):  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Metabolic Surgery ◽  
Positive Impact ◽  
Metabolic Effects ◽  
Beneficial Effects ◽  
Treatment Of Obesity ◽  
The Impact ◽  
The Brain

Abstract BACKGROUND Obesity can be defined as a chronic subcortical brain disease, as there is an important neurophysiological component to its etiology based on changes in the functioning of those areas of the brain controlling food intake and reward. Extensive metabolic changes accompany bariatric surgery-based treatment of obesity. Consequently, the term “metabolic” surgery is being increasingly adopted in relation to the beneficial effects these procedures have on chronic diseases like type 2 diabetes. CONTENT In the present review, we focus on the key biochemical and physiological changes induced by metabolic surgery and highlight the beneficial effects accrued systemically with the use of an organ-based approach. Understanding the impact on and interactions between the gut, brain, adipose tissue, liver, muscle, pancreas, and kidney is key to understanding the sum of the metabolic effects of these operations. SUMMARY Further mechanistic studies are essential to assess the true potential of metabolic surgery to treat metabolic comorbidities of obesity beyond type 2 diabetes. Approaches that may mitigate the metabolic side effects of surgery also require attention. Understanding the positive impact of metabolic surgery on metabolic health may result in a wider acceptance of this intervention as treatment for metabolic, comorbid conditions.

scholarly journals Bile Acids and GPBAR-1: Dynamic Interaction Involving Genes, Environment and Gut Microbiome

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3709 ◽  
Author(s):  
Piero Portincasa ◽  
Agostino Di Ciaula ◽  
Gabriella Garruti ◽  
Mirco Vacca ◽  
Maria De Angelis ◽  
...  
Keyword(s):  
Bile Acids ◽  
Gut Microbiome ◽  
Portal Tract ◽  
Farnesoid X Receptor ◽  
Metabolic Effects ◽  
Remnant Liver ◽  
Prevention Measures ◽  
Distal Intestine ◽  
Gene Environment ◽  
Fat Soluble Vitamins

Bile acids (BA) are amphiphilic molecules synthesized in the liver from cholesterol. BA undergo continuous enterohepatic recycling through intestinal biotransformation by gut microbiome and reabsorption into the portal tract for uptake by hepatocytes. BA are detergent molecules aiding the digestion and absorption of dietary fat and fat-soluble vitamins, but also act as important signaling molecules via the nuclear receptor, farnesoid X receptor (FXR), and the membrane-associated G protein-coupled bile acid receptor 1 (GPBAR-1) in the distal intestine, liver and extra hepatic tissues. The hydrophilic-hydrophobic balance of the BA pool is finely regulated to prevent BA overload and liver injury. By contrast, hydrophilic BA can be hepatoprotective. The ultimate effects of BA-mediated activation of GPBAR-1 is poorly understood, but this receptor may play a role in protecting the remnant liver and in maintaining biliary homeostasis. In addition, GPBAR-1 acts on pathways involved in inflammation, biliary epithelial barrier permeability, BA pool hydrophobicity, and sinusoidal blood flow. Recent evidence suggests that environmental factors influence GPBAR-1 gene expression. Thus, targeting GPBAR-1 might improve liver protection, facilitating beneficial metabolic effects through primary prevention measures. Here, we discuss the complex pathways linked to BA effects, signaling properties of the GPBAR-1, mechanisms of liver damage, gene-environment interactions, and therapeutic aspects.

scholarly journals Omentin - a new adipokine with many roles to play

2015 ◽  
Vol 28 (3) ◽  
pp. 176-180 ◽  
Author(s):  
Magdalena Halabis ◽  
Marcin Dziedzic ◽  
Joanna Warchulinska ◽  
Iwona Kaznowska-Bystryk ◽  
Janusz Solski
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Polycystic Ovary ◽  
Overweight And Obesity ◽  
Ovary Syndrome ◽  
Treatment Of Obesity ◽  
All Diseases ◽  
Multiple Interactions

Abstract Adipose tissue is at a point of high interest in medical research, not only as an energy depot, but also because it secretes nearly more than 600 cytokines. These are termed‚ adipokines’. Human adipokines are involved in numerous metabolic processes, including the regulation of appetite, energy expenditure, insulin sensitivity, inflammation and cardiovascular activity. Thus, these could be clinically important as a markers of adipose tissue function and increased metabolic risk. The search for novel adipokines linking obesity to related co-morbidities has become a major topic in obesity research. In such work, there is an increasing need to define their function, their molecular targets and their potential clinical relevance as biomarkers or in the treatment of obesity and other metabolic diseases. Omentin (34 kDa) is a recently identified fat deposition-specific adipokine with multiple interactions. Concentrations of omentin have been shown to be decreased in patients with obesity and impaired glucose regulation, in patients afflicted with diabetes type 1 and 2, and in patients with polycystic ovary syndrome. These are all diseases commonly associated with insulin resistance and obesity. The aim of this study was to show and compare the latest information about omentin and its relationships with obesity, diabetes mellitus (DM), metabolic syndrome (MetS), inflammation, cardiac problems, sex hormone imbalances and cancer. The association of omentin with particular metabolic indexes may suggest that an elevation in omentin level may be seen as being a marker for leanness, while a decreased level will underline possible situations of overweight and obesity along with their comorbidities (diabetes, cardiovascular disease, metabolic syndrome, inflammation and even cancer). However, a challenge for the future is to fully understand the multiple role played by omentin. Thus, more studies in these matter are required.

scholarly journals Potential anti-obesogenic properties of non-digestible carbohydrates: specific focus on resistant dextrin

2015 ◽  
Vol 74 (3) ◽  
pp. 258-267 ◽  
Author(s):  
Mark R. Hobden ◽  
Laetitia Guérin-Deremaux ◽  
Ian Rowland ◽  
Glenn R. Gibson ◽  
Orla B. Kennedy
Keyword(s):  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Intervention Studies ◽  
Metabolic Diseases ◽  
Metabolic Effects ◽  
Appetite Regulation ◽  
Bacterial Populations ◽  
Glucose And Lipid Metabolism ◽  
Resistant Dextrin ◽  
The Impact

Alterations in the composition and metabolic activity of the gut microbiota appear to contribute to the development of obesity and associated metabolic diseases. However, the extent of this relationship remains unknown. Modulating the gut microbiota with non-digestible carbohydrates (NDC) may exert anti-obesogenic effects through various metabolic pathways including changes to appetite regulation, glucose and lipid metabolism and inflammation. The NDC vary in physicochemical structure and this may govern their physical properties and fermentation by specific gut bacterial populations. Much research in this area has focused on established prebiotics, especially fructans (i.e. inulin and fructo-oligosaccharides); however, there is increasing interest in the metabolic effects of other NDC, such as resistant dextrin. Data presented in this review provide evidence from mechanistic and intervention studies that certain fermentable NDC, including resistant dextrin, are able to modulate the gut microbiota and may alter metabolic process associated with obesity, including appetite regulation, energy and lipid metabolism and inflammation. To confirm these effects and elucidate the responsible mechanisms, further well-controlled human intervention studies are required to investigate the impact of NDC on the composition and function of the gut microbiota and at the same time determine concomitant effects on host metabolism and physiology.

scholarly journals The Anti-Obesity Effect of Traditional Chinese Medicine on Lipid Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Qijing Fan ◽  
Furong Xu ◽  
Bin Liang ◽  
Xiaoju Zou
Keyword(s):  
Lipid Metabolism ◽  
Bioactive Compounds ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Lipid Synthesis ◽  
Lipid Absorption ◽  
Alcoholic Fatty Liver ◽  
Global Epidemic ◽  
Unhealthy Eating ◽  
Treatment Of Obesity

With the improvement of living conditions and the popularity of unhealthy eating and living habits, obesity is becoming a global epidemic. Obesity is now recognized as a disease that not only increases the risk of metabolic diseases such as type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD), cardiovascular disease (CVD), and cancer but also negatively affects longevity and the quality of life. The traditional Chinese medicines (TCMs) are highly enriched in bioactive compounds and have been used for the treatment of obesity and obesity-related metabolic diseases over a long period of time. In this review, we selected the most commonly used anti-obesity or anti-hyperlipidemia TCMs and, where known, their major bioactive compounds. We then summarized their multi-target molecular mechanisms, specifically focusing on lipid metabolism, including the modulation of lipid absorption, reduction of lipid synthesis, and increase of lipid decomposition and lipid transportation, as well as the regulation of appetite. This review produces a current and comprehensive understanding of integrative and systematic mechanisms for the use of TCMs for anti-obesity. We also advocate taking advantage of TCMs as another therapy for interventions on obesity-related diseases, as well as stressing the fact that more is needed to be done, scientifically, to determine the active compounds and modes of action of the TCMs.

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