Non-alcoholic fatty liver disease: pathophysiological concepts and treatment options

Cardiovascular Research, Journal Year: 2023, Volume and Issue: 119(9), P. 1787 - 1798

Published: June 26, 2023

Abstract The prevalence of non-alcoholic fatty liver disease (NAFLD) is continually increasing due to the global obesity epidemic. NAFLD comprises a systemic metabolic accompanied frequently by insulin resistance and hepatic inflammation. Whereas simple steatosis most common manifestation, more progressive course characterized fibrosis inflammation (i.e. steatohepatitis) present in 10–20% affected individuals. furthermore progresses substantial number patients towards cirrhosis hepatocellular carcinoma. this now affects almost 25% world’s population mainly observed type 2 diabetes, also lean Pathophysiology involves lipotoxicity, immune disturbances resistance, gut dysbiosis, commonly defining disorder prototypic disorder. Not surprisingly many have other manifestations, indeed cardiovascular disease, chronic kidney extrahepatic malignancies are all contributing substantially patient outcome. Weight loss lifestyle change reflect cornerstone treatment, several medical treatment options currently under investigation. promising strategies include glucagon-like peptide 1 receptor antagonists, sodium–glucose transporter inhibitors, Fibroblast Growth Factor analogues, Farnesoid X agonists, peroxisome proliferator–activated agonists. Here, we review epidemiology, pathophysiology, therapeutic for NAFLD.

Language: Английский

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Metabolite interactions between host and microbiota during health and disease: Which feeds the other?

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 160, P. 114295 - 114295

Published: Jan. 27, 2023

Metabolites produced by the host and microbiota play a crucial role in how human bodies develop remain healthy. Most of these metabolites are hosts digestive tract. gut have important roles energy metabolism, cellular communication, immunity, among other physiological activities. Although numerous metabolites, such as free fatty acids, amino vitamins, found intestine, generated equally vital for intestinal homeostasis. Furthermore, is sole source some including short-chain acids (SCFAs). microbiota, neurotransmitters hormones, may modulate significantly affect metabolism. The becoming recognized second endocrine system. A variety chronic inflammatory disorders been linked to aberrant host-microbiota interplays, but precise mechanisms underpinning disturbances they might lead diseases be fully elucidated. Microbiome-modulated promising targets new drug discovery due their function various complex disorders. In humans, metabolotherapy prevention or treatment will possible if we better understand metabolic preferences bacteria specific tissues organs. Better disease treatments with help novel complementary therapies that target bacterial consequences, functional interplays highlighted, summarized, discussed this overview.

Language: Английский

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A male germ-cell-specific ribosome controls male fertility

Nature, Journal Year: 2022, Volume and Issue: 612(7941), P. 725 - 731

Published: Dec. 14, 2022

Language: Английский

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Gut Microbiota–Derived Trimethylamine N-Oxide Contributes to Abdominal Aortic Aneurysm Through Inflammatory and Apoptotic Mechanisms

Circulation, Journal Year: 2023, Volume and Issue: 147(14), P. 1079 - 1096

Published: April 3, 2023

Large-scale human and mechanistic mouse studies indicate a strong relationship between the microbiome-dependent metabolite trimethylamine N-oxide (TMAO) several cardiometabolic diseases. This study aims to investigate role of TMAO in pathogenesis abdominal aortic aneurysm (AAA) target its parent microbes as potential pharmacological intervention.

Language: Английский

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Gut microbiota-derived metabolites as key actors in type 2 diabetes mellitus

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 149, P. 112839 - 112839

Published: March 21, 2022

Type 2 diabetes mellitus (T2DM) is one of the most risk factors threatening human health. Although genetic and environmental contribute to development T2DM, gut microbiota has also been found be involved. Gut microbiota-derived metabolites are a key factor in host-microbe crosstalk, have revealed play central role physiology physiopathology T2DM. In this review, we provide timely comprehensive summary microbial that protective or causative for including some amino acids-derived metabolites, short-chain fatty acids, trimethylamine N-oxide, bile acids. The mechanisms by which affect T2DM elaborated. Knowing more about these processes will increase our understanding causal relationship between Moreover, frontier therapies target microbes their improve dietary intervention, fecal transplantation, probiotics, prebiotics synbiotics drugging metabolism, critically discussed. This review may novel insights targeted personalized treatments based on metabolites. More high-quality clinical trials needed accelerate translation gut-targeted

Language: Английский

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Contribution of Trimethylamine N-Oxide (TMAO) to Chronic Inflammatory and Degenerative Diseases

Biomedicines, Journal Year: 2023, Volume and Issue: 11(2), P. 431 - 431

Published: Feb. 2, 2023

Trimethylamine N-oxide (TMAO) is a metabolite produced by the gut microbiota and has been mainly associated with an increased incidence of cardiovascular diseases (CVDs) in humans. There are factors that affect one’s TMAO level, such as diet, drugs, age, hormones, among others. Gut dysbiosis host studied recently new approach to understanding chronic inflammatory degenerative diseases, including metabolic Alzheimer’s disease. These disease types well COVID-19 known modulate immunity. Diabetic obese patients have observed increase their level TMAO, which direct correlation CVDs. This attributed enhancing pathways through cholesterol bile acid dysregulation, promoting foam cell formation. Additionally, activates transcription factor NF-κB, which, turn, triggers cytokine production. The result can be exaggerated response capable inducing endoplasmic reticulum stress, responsible for various diseases. Due deleterious effects this causes its host, it important search therapeutic agents allow reduction levels that, thus, able avoid severe event. present review discussed synthesis contribution pathogenesis

Language: Английский

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Gut microbiota and metabolic biomarkers in metabolic dysfunction–associated steatotic liver disease

Hepatology Communications, Journal Year: 2024, Volume and Issue: 8(3)

Published: Feb. 26, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), a replacement of the nomenclature employed for NAFLD, is most prevalent chronic worldwide. Despite its high global prevalence, NAFLD often under-recognized due to absence reliable noninvasive biomarkers diagnosis and staging. Growing evidence suggests that gut microbiome plays significant role in occurrence progression by causing immune dysregulation metabolic alterations dysbiosis. The rapid advancement sequencing tools metabolomics has enabled identification signatures microbiota-derived metabolite profiles numerous clinical studies related NAFLD. Overall, these have shown decrease α-diversity changes microbiota abundance, characterized increased levels Escherichia Prevotella, decreased Akkermansia muciniphila Faecalibacterium patients with Furthermore, bile acids, short-chain fatty trimethylamine N-oxide, tryptophan metabolites are believed be closely associated onset In this review, we provide novel insights into vital pathogenesis Specifically, summarize major classes thereby highlighting links between specific bacterial species certain

Language: Английский

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The communication mechanism of the gut-brain axis and its effect on central nervous system diseases: A systematic review

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117207 - 117207

Published: July 26, 2024

Language: Английский

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Trimethylamine N-oxide impairs β-cell function and glucose tolerance

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 21, 2024

Abstract β-Cell dysfunction and β-cell loss are hallmarks of type 2 diabetes (T2D). Here, we found that trimethylamine N-oxide (TMAO) at a similar concentration to in could directly decrease glucose-stimulated insulin secretion (GSIS) MIN6 cells primary islets from mice or humans. Elevation TMAO levels impairs GSIS, proportion, glucose tolerance male C57BL/6 J mice. inhibits calcium transients through NLRP3 inflammasome-related cytokines induced Serca2 loss, agonist reversed the effect on function vitro vivo. Additionally, long-term exposure promotes ER stress, dedifferentiation, apoptosis transcriptional identity. Inhibition production improves both db/db choline diet-fed These observations identify role for maintenance, inhibition be an approach treatment T2D.

Language: Английский

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Cellular and organismal function of choline metabolism

Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Language: Английский

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