scholarly journals The Interaction between the Gut Microbiome and Bile Acids in Cardiometabolic Diseases

Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 65
Author(s):  
Cengiz Callender ◽  
Ilias Attaye ◽  
Max Nieuwdorp
Keyword(s):  
Bile Acids ◽  
Gut Microbiome ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Comprehensive Overview ◽  
Endocrine Organ ◽  
Cardiometabolic Diseases ◽  
Signalling Molecules ◽  
The Past

Cardio-metabolic diseases (CMD) are a spectrum of diseases (e.g., type 2 diabetes, atherosclerosis, non-alcohol fatty liver disease (NAFLD), and metabolic syndrome) that are among the leading causes of morbidity and mortality worldwide. It has long been known that bile acids (BA), which are endogenously produced signalling molecules from cholesterol, can affect CMD risk and progression and directly affect the gut microbiome (GM). Moreover, studies focusing on the GM and CMD risk have dramatically increased in the past decade. It has also become clear that the GM can function as a “new” endocrine organ. BA and GM have a complex and interdependent relationship with several CMD pathways. This review aims to provide a comprehensive overview of the interplay between BA metabolism, the GM, and CMD risk and progression.

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.

Intramyocellular fat storage in metabolic diseases

2016 ◽  
Vol 26 (1) ◽  
Author(s):  
Claire Laurens ◽  
Cedric Moro
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Metabolic Diseases ◽  
Recent Literature ◽  
Lipid Storage ◽  
Muscle Lipid ◽  
The Past ◽  
Skeletal Muscle Lipid ◽  
Ectopic Lipid Storage

AbstractOver the past decades, obesity and its metabolic co-morbidities such as type 2 diabetes (T2D) developed to reach an endemic scale. However, the mechanisms leading to the development of T2D are still poorly understood. One main predictor for T2D seems to be lipid accumulation in “non-adipose” tissues, best known as ectopic lipid storage. A growing body of data suggests that these lipids may play a role in impairing insulin action in metabolic tissues, such as liver and skeletal muscle. This review aims to discuss recent literature linking ectopic lipid storage and insulin resistance, with emphasis on lipid deposition in skeletal muscle. The link between skeletal muscle lipid content and insulin sensitivity, as well as the mechanisms of lipid-induced insulin resistance and potential therapeutic strategies to alleviate lipotoxic lipid pressure in skeletal muscle will be discussed.

Bile Acids, Gut Microbiome and the Road to Fatty Liver Disease

2021 ◽  
pp. 2719-2730
Author(s):  
Phillip B. Hylemon ◽  
Lianyong Su ◽  
Po‐Cheng Zheng ◽  
Jasmohan S. Bajaj ◽  
Huiping Zhou
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Bile Acids ◽  
Gut Microbiome ◽  
Fatty Liver Disease ◽  
The Road

scholarly journals Muscle–Organ Crosstalk: The Emerging Roles of Myokines

2020 ◽  
Vol 41 (4) ◽  
pp. 594-609 ◽  
Author(s):  
Mai Charlotte Krogh Severinsen ◽  
Bente Klarlund Pedersen
Keyword(s):  
Skeletal Muscle ◽  
Cell Function ◽  
Exercise Prescription ◽  
Endothelial Cell Function ◽  
Endocrine Organ ◽  
The Past ◽  
Vascular Bed ◽  
White Fat ◽  
Response To Exercise

Abstract Physical activity decreases the risk of a network of diseases, and exercise may be prescribed as medicine for lifestyle-related disorders such as type 2 diabetes, dementia, cardiovascular diseases, and cancer. During the past couple of decades, it has been apparent that skeletal muscle works as an endocrine organ, which can produce and secrete hundreds of myokines that exert their effects in either autocrine, paracrine, or endocrine manners. Recent advances show that skeletal muscle produces myokines in response to exercise, which allow for crosstalk between the muscle and other organs, including brain, adipose tissue, bone, liver, gut, pancreas, vascular bed, and skin, as well as communication within the muscle itself. Although only few myokines have been allocated to a specific function in humans, it has been identified that the biological roles of myokines include effects on, for example, cognition, lipid and glucose metabolism, browning of white fat, bone formation, endothelial cell function, hypertrophy, skin structure, and tumor growth. This suggests that myokines may be useful biomarkers for monitoring exercise prescription for people with, for example, cancer, diabetes, or neurodegenerative diseases.

Blood triacylglycerols: a lipidomic window on diet and disease

2016 ◽  
Vol 44 (2) ◽  
pp. 638-644 ◽  
Author(s):  
Francis Sanders ◽  
Ben McNally ◽  
Julian L. Griffin
Keyword(s):  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Clinical Chemistry ◽  
Total Concentration ◽  
Direct Infusion ◽  
Alcoholic Fatty Liver ◽  
Tissue Extracts ◽  
The Individual ◽  
Alcoholic Fatty Liver Disease

Although the measurement of triacylglycerols (TAGs) by clinical chemistry has been used in the diagnosis of a range of metabolic diseases, such approaches ignore the different species of TAGs that contribute to the total concentration. With the advent of LC and direct infusion forms of MS it is now possible to profile the individual TAGs in blood plasma or tissue extracts. This mini review surveys the information that is obtainable from the lipidomic profiling of TAGs in following metabolic diseases such as type 2 diabetes (T2DM), cardiovascular disease (CVD) and non-alcoholic fatty liver disease, as well as the development of insulin resistance and obesity.

scholarly journals The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Longman Li ◽  
Xiaobo Yang
Keyword(s):  
Oxidative Stress ◽  
Metabolic Diseases ◽  
Essential Element ◽  
Ros Generation ◽  
Oxygen Species ◽  
Mitochondrial Oxidative Stress ◽  
Nonalcoholic Fatty Liver ◽  
The Past ◽  
The Relationship

Manganese (Mn) is an essential element that is involved in the synthesis and activation of many enzymes and in the regulation of the metabolism of glucose and lipids in humans. In addition, Mn is one of the required components for Mn superoxide dismutase (MnSOD) that is mainly responsible for scavenging reactive oxygen species (ROS) in mitochondrial oxidative stress. Both Mn deficiency and intoxication are associated with adverse metabolic and neuropsychiatric effects. Over the past few decades, the prevalence of metabolic diseases, including type 2 diabetes mellitus (T2MD), obesity, insulin resistance, atherosclerosis, hyperlipidemia, nonalcoholic fatty liver disease (NAFLD), and hepatic steatosis, has increased dramatically. Previous studies have found that ROS generation, oxidative stress, and inflammation are critical for the pathogenesis of metabolic diseases. In addition, deficiency in dietary Mn as well as excessive Mn exposure could increase ROS generation and result in further oxidative stress. However, the relationship between Mn and metabolic diseases is not clear. In this review, we provide insights into the role Mn plays in the prevention and development of metabolic diseases.

scholarly journals Visfatin/Nampt: An Adipokine with Cardiovascular Impact

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Tania Romacho ◽  
Carlos F. Sánchez-Ferrer ◽  
Concepción Peiró
Keyword(s):  
Metabolic Diseases ◽  
Vascular Inflammation ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Endocrine Organ ◽  
Clinical Marker ◽  
Insulin Mimetic ◽  
Active Player ◽  
Plaque Destabilization ◽  
Circulating Levels

Adipose tissue is acknowledged as an endocrine organ that releases bioactive factors termed adipokines. Visfatin was initially identified as a novel adipokine with insulin-mimetic properties in mice. This adipokine was identical to two previously described molecules, namely, pre-B cell colony-enhancing factor (PBEF) and the enzyme nicotinamide phosphoribosyltransferase (Nampt). Enhanced circulating visfatin/Nampt levels have been reported in metabolic diseases, such as obesity and type 2 diabetes. Moreover, visfatin/Nampt circulating levels correlate with markers of systemic inflammation. In cardiovascular diseases, visfatin/Nampt was initially proposed as a clinical marker of atherosclerosis, endothelial dysfunction, and vascular damage, with a potential prognostic value. Nevertheless, beyond being a surrogate clinical marker, visfatin/Nampt is an active player promoting vascular inflammation, and atherosclerosis. Visfatin/Nampt effects on cytokine and chemokine secretion, macrophage survival, leukocyte recruitment by endothelial cells, vascular smooth muscle inflammation and plaque destabilization make of this adipokine an active factor in the development and progression of atherosclerosis. Further research is required to fully understand the mechanisms mediating the cellular actions of this adipokine and to better characterize the factors regulating visfatin/Nampt expression and release in all these pathologic scenarios. Only then, we will be able to conclude whether visfatin/Nampt is a therapeutical target in cardiometabolic diseases.

scholarly journals Computational Tools in the Discovery of FABP4 Ligands: A Statistical and Molecular Modeling Approach

2019 ◽  
Author(s):  
Giuseppe Floresta ◽  
Davide Gentile ◽  
Giancarlo Perrini ◽  
Vincenzo Patamia ◽  
Antonio Rescifina
Keyword(s):  
Fatty Acid Binding Protein ◽  
Metabolic Diseases ◽  
New Drugs ◽  
Computational Tools ◽  
Computer Aided Drug Design ◽  
Fatty Acid Binding ◽  
Beneficial Effects ◽  
Acid Binding Protein ◽  
The Past

Small molecule inhibitors of adipocyte fatty-acid binding protein 4 (FABP4) have got interest following the recent publication of their pharmacologically beneficial effects. Recently it comes out that FABP4 is an attractive molecular target for the treatment of type 2 diabetes, other metabolic diseases, and some type of cancers. In the past years, hundreds of effective FABP4 inhibitors have been synthesized and discovered but, unfortunately, none of them is in the clinical research phase. The field of computer-aided drug design seems to be promising and useful for the identification of FABP4 inhibitors; hence, different structure- and ligand-based computational approaches were already performed for their identification. In this paper, we searched for new potentially active FABP4 ligands in the Marine Natural Products (MNP) database. 14,492 compounds were retrieved from this database and filtered through a statistical and computational filter. Seven compounds were suggested by our methodology to possess a potential inhibitory activity upon FABP4 in the range of 79–245 nM. ADMET properties prediction were performed to validate the hypothesis of the interaction with the intended target and to assess the drug-likeness of these derivatives; from these analyses, three molecules resulted as excellent candidates for becoming new drugs.

scholarly journals Pattern Recognition Receptor-Mediated Chronic Inflammation in the Development and Progression of Obesity-Related Metabolic Diseases

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Lili Yu ◽  
Yanhua Li ◽  
Cancan Du ◽  
Weidong Zhao ◽  
Hanxiao Zhang ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Chronic Inflammation ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Important Determinant ◽  
Pattern Recognition Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Recognition Receptor ◽  
Oligomerization Domain

Obesity-induced chronic inflammation is known to promote the development of many metabolic diseases, especially insulin resistance, type 2 diabetes mellitus, nonalcoholic fatty liver disease, and atherosclerosis. Pattern recognition receptor-mediated inflammation is an important determinant for the initiation and progression of these metabolic diseases. Here, we review the major features of the current understanding with respect to obesity-related chronic inflammation in metabolic tissues, focus on Toll-like receptors and nucleotide-binding oligomerization domain-like receptors with an emphasis on how these receptors determine metabolic disease progression, and provide a summary on the development and progress of PRR antagonists for therapeutic intervention.

scholarly journals The Liver–α-Cell Axis and Type 2 Diabetes

2019 ◽  
Vol 40 (5) ◽  
pp. 1353-1366 ◽  
Author(s):  
Nicolai J Wewer Albrechtsen ◽  
Jens Pedersen ◽  
Katrine D Galsgaard ◽  
Marie Winther-Sørensen ◽  
Malte P Suppli ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Liver Disease ◽  
Amino Acid ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Plasma Concentrations ◽  
Amino Acid Turnover

Abstract Both type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD) strongly associate with increasing body mass index, and together these metabolic diseases affect millions of individuals. In patients with T2D, increased secretion of glucagon (hyperglucagonemia) contributes to diabetic hyperglycemia as proven by the significant lowering of fasting plasma glucose levels following glucagon receptor antagonist administration. Emerging data now indicate that the elevated plasma concentrations of glucagon may also be associated with hepatic steatosis and not necessarily with the presence or absence of T2D. Thus, fatty liver disease, most often secondary to overeating, may result in impaired amino acid turnover, leading to increased plasma concentrations of certain glucagonotropic amino acids (e.g., alanine). This, in turn, causes increased glucagon secretion that may help to restore amino acid turnover and ureagenesis, but it may eventually also lead to increased hepatic glucose production, a hallmark of T2D. Early experimental findings support the hypothesis that hepatic steatosis impairs glucagon’s actions on amino acid turnover and ureagenesis. Hepatic steatosis also impairs hepatic insulin sensitivity and clearance that, together with hyperglycemia and hyperaminoacidemia, lead to peripheral hyperinsulinemia; systemic hyperinsulinemia may itself contribute to worsen peripheral insulin resistance. Additionally, obesity is accompanied by an impaired incretin effect, causing meal-related glucose intolerance. Lipid-induced impairment of hepatic sensitivity, not only to insulin but potentially also to glucagon, resulting in both hyperinsulinemia and hyperglucagonemia, may therefore contribute to the development of T2D at least in a subset of individuals with NAFLD.

Sign in / Sign up

Export Citation Format

Share Document