The role of the microbiome in NAFLD and NASH

EMBO Molecular Medicine, Journal Year: 2018, Volume and Issue: 11(2)

Published: Dec. 27, 2018

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of cardiometabolic syndrome, which often also includes obesity, diabetes, and dyslipidemia. It rapidly becoming most prevalent worldwide. A sizable minority NAFLD patients develop nonalcoholic steatohepatitis (NASH), characterized by inflammatory changes that can lead to progressive damage, cirrhosis, hepatocellular carcinoma. Recent studies have shown in addition genetic predisposition diet, gut microbiota affects carbohydrate lipid metabolism as well influences balance between pro-inflammatory anti-inflammatory effectors liver, thereby impacting its progression NASH In this review, we will explore impact microbiota-derived compounds on development NASH, unexplored factors related potential microbiome contributions common disease.

Language: Английский

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Metabolomics and lipidomics in NAFLD: biomarkers and non-invasive diagnostic tests

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2021, Volume and Issue: 18(12), P. 835 - 856

Published: Sept. 10, 2021

Language: Английский

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Glycine Metabolism and Its Alterations in Obesity and Metabolic Diseases

Nutrients, Journal Year: 2019, Volume and Issue: 11(6), P. 1356 - 1356

Published: June 16, 2019

Glycine is the proteinogenic amino-acid of lowest molecular weight, harboring a hydrogen atom as side-chain. In addition to being building-block for proteins, glycine also required multiple metabolic pathways, such glutathione synthesis and regulation one-carbon metabolism. Although generally viewed non-essential amino-acid, because it can be endogenously synthesized certain extent, has been suggested conditionally essential amino acid. disorders associated with obesity, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLDs), lower circulating levels have consistently observed, clinical studies suggest existence beneficial effects induced by supplementation. The present review aims at synthesizing recent advances in metabolism, pinpointing its main identifying causes leading deficiency—especially obesity disorders—and evaluating potential benefits increasing availability curb progression obesity-related disturbances. This study focuses on importance diet, gut microbiota, metabolism determining disorders.

Language: Английский

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Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(15), P. 5214 - 5214

Published: July 23, 2020

Gut microbiota dysregulation plays a key role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) through its metabolites. Therefore, restoration gut and supplementation with commensal bacterial metabolites can be therapeutic benefit against disease. In this review, we summarize roles various NAFLD their implications. The is feature NAFLD, signatures are associated severity altered Disturbance bile acid metabolism leads to underactivation receptors FXR TGR5, causal for decreased energy expenditure, increased lipogenesis, synthesis macrophage activity. Decreased production butyrate results intestinal inflammation, permeability, endotoxemia systemic inflammation. Dysregulation amino acids choline also contributes lipid accumulation chronic inflammatory status. some patients, overproduction ethanol produced by bacteria responsible hepatic Many approaches including probiotics, prebiotics, synbiotics, faecal microbiome transplantation fasting-mimicking diet have been applied restore improvement NAFLD.

Language: Английский

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Pathophysiological communication between hepatocytes and non-parenchymal cells in liver injury from NAFLD to liver fibrosis

Advanced Drug Delivery Reviews, Journal Year: 2021, Volume and Issue: 176, P. 113869 - 113869

Published: July 16, 2021

Language: Английский

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NASH in Lean Individuals

Seminars in Liver Disease, Journal Year: 2019, Volume and Issue: 39(01), P. 086 - 095

Published: Jan. 17, 2019

Abstract Nonalcoholic fatty liver disease (NAFLD) is generally associated with obesity and the related comorbidities but it can also develop in subjects a body mass index (BMI) within ethnic-specific cutoff of 25 kg/m2 BMI Caucasian 23 Asian subjects, so-called “lean” NAFLD. This sub-phenotype NAFLD patients has been described across populations different ethnicity, particularly Asia, be diagnosed 10 to 20% nonobese Americans Caucasians. Pathophysiological mechanisms underpinning phenotype are not completely understood, they may include more dysfunctional fat (visceral obesity, differences adipocyte differentiation altered lipid turnover), composition (decreased muscle mass), genetic background, limited patatin-like phospholipase domain-containing protein 3 (PNPLA3) C > G polymorphisms, epigenetic changes occurring early life pattern gut microbiota. Lean have milder features metabolic syndrome when compared obese patients. Nonetheless higher prevalence alterations (e.g., dyslipidemia, arterial hypertension, insulin resistance, diabetes) healthy controls. Data on histological severity controversial, full spectrum nonalcoholic steatohepatitis NASH. Since lean usually present less obesity-related comorbidities, commonly believed that this group would follow relatively benign clinical course recent data challenge concept. Here, authors describe current knowledge about individuals highlight unanswered questions gaps field.

Language: Английский

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Glycine-based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome

Science Translational Medicine, Journal Year: 2020, Volume and Issue: 12(572)

Published: Dec. 2, 2020

A glycine- and leucine-based tripeptide improves symptoms in a mouse model of nonalcoholic fatty liver disease, which lacks approved treatments.

Language: Английский

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Perfluoroalkyl substances and severity of nonalcoholic fatty liver in Children: An untargeted metabolomics approach

Environment International, Journal Year: 2019, Volume and Issue: 134, P. 105220 - 105220

Published: Nov. 16, 2019

Toxicant-associated steatohepatitis has been described in adults but less is known regarding the role of toxicants liver disease children. Perfluoroalkyl substances (PFAS) cause hepatic steatosis rodents, few previous studies have examined PFAS effects on severity injury We aimed to examine relationship histologic nonalcoholic fatty (NAFLD) Seventy-four children with physician-diagnosed NAFLD were recruited from Children's Healthcare Atlanta between 2007 and 2015. Biopsy-based histological features scored for steatosis, lobular portal inflammation, ballooning, fibrosis. Plasma concentrations perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) perfluorohexane sulfonic (PFHxS), untargeted plasma metabolomic profiling, determined using liquid chromatography high-resolution mass spectrometry. A metabolome-wide association study coupled pathway enrichment analysis was performed evaluate metabolic dysregulation associated PFAS. structural integrated applied identify latent clusters more severe form based their levels metabolite pattern. Patients 7–19 years old, mostly boys (71%), Hispanic (51%), obese (85%). The odds having (NASH), compared alone, significantly increased each interquartile range (IQR) increase PFOS (OR: 3.32, 95% CI: 1.40–7.87) PFHxS 4.18, 1.64–10.7). Each IQR fibrosis 4.44, 1.34–14.8), inflammation 2.87, 1.12–7.31), higher activity score (β coefficient 0.46; 0.03, 0.89). novel integrative identified a cluster NASH, characterized by altered patterns including phosphoethanolamine, tyrosine, phenylalanine, aspartate creatine, decreased betaine. Ηigher exposure NAFLD. may be an important toxicant contributing progression; however larger, longitudinal are warranted confirm these findings.

Language: Английский

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The Critical Role of the Branched Chain Amino Acids (BCAAs) Catabolism-Regulating Enzymes, Branched-Chain Aminotransferase (BCAT) and Branched-Chain α-Keto Acid Dehydrogenase (BCKD), in Human Pathophysiology

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 4022 - 4022

Published: April 5, 2022

Branched chain amino acids (BCAAs), leucine, isoleucine and valine, are essential widely studied for their crucial role in the regulation of protein synthesis mainly through activation mTOR signaling pathway emerging recognition as players various physiological metabolic processes, such glucose homeostasis. BCAA supplementation is primarily used a beneficial nutritional intervention chronic liver kidney disease well muscle wasting disorders. However, downregulated/upregulated plasma BCAAs defective catabolism tissues, due to altered enzymatic activity first two enzymes catabolic pathway, aminotransferase (BCAT) branched-chain α-keto acid dehydrogenase (BCKD), have been investigated many states. The current review focused on underlying mechanisms its contribution pathogenesis numerous pathological conditions diabetes, heart failure cancer. In addition, we summarize findings that indicate recovery dysregulated may be associated with an improved outcome prevention serious complications.

Language: Английский

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Insulin-regulated serine and lipid metabolism drive peripheral neuropathy

Nature, Journal Year: 2023, Volume and Issue: 614(7946), P. 118 - 124

Published: Jan. 25, 2023

Abstract Diabetes represents a spectrum of disease in which metabolic dysfunction damages multiple organ systems including liver, kidneys and peripheral nerves 1,2 . Although the onset progression these co-morbidities are linked with insulin resistance, hyperglycaemia dyslipidaemia 3–7 , aberrant non-essential amino acid (NEAA) metabolism also contributes to pathogenesis diabetes 8–10 Serine glycine closely related NEAAs whose levels consistently reduced patients syndrome 10–14 but mechanistic drivers downstream consequences this metabotype remain unclear. Low systemic serine emerging as hallmark macular nerve disorders, correlating impaired visual acuity neuropathy 15,16 Here we demonstrate that homeostasis drives deficiencies diabetic mice, can be diagnosed tolerance test quantifies uptake disposal. Mimicking alterations young mice by dietary or restriction together high fat intake markedly accelerates small fibre while reducing adiposity. Normalization supplementation mitigation myriocin both alleviate linking serine-associated sphingolipid metabolism. These findings identify deficiency novel risk factors for may exploited therapeutically.

Language: Английский

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