Metabolic Dysfunction–Associated Steatotic Liver Disease: From Pathogenesis to Current Therapeutic Options

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(11), С. 5640 - 5640

Опубликована: Май 22, 2024

The epidemiological burden of liver steatosis associated with metabolic diseases is continuously growing worldwide and in all age classes. This condition generates possible progression damage (i.e., inflammation, fibrosis, cirrhosis, hepatocellular carcinoma) but also independently increases the risk cardio-metabolic cancer. In recent years, terminological evolution from “nonalcoholic fatty disease” (NAFLD) to “metabolic dysfunction-associated (MAFLD) and, finally, steatotic (MASLD) has been paralleled by increased knowledge mechanisms linking local hepatic) systemic pathogenic pathways. As a consequence, need for an appropriate classification individual phenotypes oriented investigation innovative therapeutic tools. Besides well-known role lifestyle change, number pharmacological approaches have explored, ranging antidiabetic drugs agonists acting on gut–liver axis at level (mainly farnesoid X receptor (FXR) agonists, PPAR thyroid hormone agonists), anti-fibrotic anti-inflammatory agents. intrinsically complex pathophysiological history MASLD makes selection single effective treatment major challenge, so far. this evolving scenario, cooperation between different stakeholders (including subjects risk, health professionals, pharmaceutical industries) could significantly improve management disease implementation primary secondary prevention measures. high healthcare search new, effective, safe pressing need, together accurate characterization phenotypes. Recent promising advances indicate that we may soon enter era precise personalized therapy MASLD/MASH.

Язык: Английский

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The Potential of the Mediterranean Diet to Improve Mitochondrial Function in Experimental Models of Obesity and Metabolic Syndrome

Nutrients, Год журнала: 2022, Номер 14(15), С. 3112 - 3112

Опубликована: Июль 28, 2022

The abnormal expansion of body fat paves the way for several metabolic abnormalities including overweight, obesity, and diabetes, which ultimately cluster under umbrella syndrome (MetS). Patients with MetS are at an increased risk cardiovascular disease, morbidity, mortality. coexistence distinct is associated release pro-inflammatory adipocytokines, as components low-to-medium grade systemic inflammation oxidative stress. Adopting healthy lifestyles, by using appropriate dietary regimens, contributes to prevention treatment MetS. Metabolic can influence function energetic capacity mitochondria, observed in many obesity-related cardio-metabolic disorders. There preclinical studies both cellular animal models, well clinical studies, dealing nutrients Mediterranean diet (MD) dysfunctional mitochondria obesity term "

Язык: Английский

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Gut microbes in metabolic disturbances. Promising role for therapeutic manipulations?

European Journal of Internal Medicine, Год журнала: 2023, Номер 119, С. 13 - 30

Опубликована: Окт. 4, 2023

Язык: Английский

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NAFLD, MAFLD, and beyond: one or several acronyms for better comprehension and patient care

Internal and Emergency Medicine, Год журнала: 2023, Номер 18(4), С. 993 - 1006

Опубликована: Фев. 17, 2023

Abstract The term non-alcoholic fatty liver disease (NAFLD) has rapidly become the most common type of chronic disease. NAFLD points to excessive hepatic fat storage and no evidence secondary accumulation in patients with “no or little alcohol consumption”. Both etiology pathogenesis are largely unknown, a definitive therapy is lacking. Since very often closely associated metabolic dysfunctions, consensus process ongoing shift acronym MAFLD, i.e., metabolic-associated change terminology likely improve classification affected individuals, awareness, comprehension pathophysiological aspects involved, choice more personalized therapeutic approaches while avoiding intrinsic stigmatization due “non-alcoholic”. Even recently, other sub-classifications have been proposed concentrate heterogeneous causes under one umbrella. While awaiting additional validation studies this field, we discuss main reasons underlying important paradigm.

Язык: Английский

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Lycopene prevents non-alcoholic fatty liver disease through regulating hepatic NF-κB/NLRP3 inflammasome pathway and intestinal microbiota in mice fed with high-fat and high-fructose diet

Frontiers in Nutrition, Год журнала: 2023, Номер 10

Опубликована: Март 23, 2023

Lycopene (LY) belongs to carotenoids and is abundant in red fruits vegetables. Several previous studies suggested that LY beneficial for ameliorating non-alcoholic fatty liver disease (NAFLD), while the potential mechanisms are unclear. The present study aimed clarify of preventing NAFLD via exploring hepatic NF-κB/NLRP3 inflammasome pathway intestinal microbiota composition high-fat high-fructose diet (HFFD)-fed mice. Fifty eight-week-old male C57BL/6J mice were randomly assigned into 5 groups: Normal control group (NC); HFFD group; with low dose lycopene (LLY, 20 mg/kg/d); high (HLY, 60 mg/kg/d) resveratrol (RSV, 50 mg/kg/d, positive control). After 8 weeks, feces collected 12 h fasted sacrificed acquire tissues blood parameters measurement. results showed LLY, HLY RSV groups had significantly lower body weight gain, white adipose tissue, serum levels density lipoprotein-cholesterol (HDL-C), (LDL-C), lipopolysaccharide (LPS), alanine aminotransferase (ALT), concentrations triglyceride (TG) interleukin-6 (IL-6) than (p < 0.05). also displayed TG, total cholesterol (TC) tumor necrosis factor-α (TNF-α) Liver protein expressions NLRP3, Pro-Caspase-1, Caspase-1 NF-κB those -treated higher relative SCFAs producing bacteria Allobaculum destructive bacteria, including Firmicutes, Lachnospiraceae_NK4A136_group, Desulfovibrio, Alistipes over fecal In conclusion, might prevent by suppressing attenuating gut dysbiosis.

Язык: Английский

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Raspberry polysaccharides attenuate hepatic inflammation and oxidative stress in diet-induced obese mice by enhancing butyrate-mediated intestinal barrier function

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 262, С. 130007 - 130007

Опубликована: Фев. 8, 2024

Язык: Английский

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Recent Advances in the Digestive, Metabolic and Therapeutic Effects of Farnesoid X Receptor and Fibroblast Growth Factor 19: From Cholesterol to Bile Acid Signaling

Nutrients, Год журнала: 2022, Номер 14(23), С. 4950 - 4950

Опубликована: Ноя. 22, 2022

Bile acids (BA) are amphiphilic molecules synthesized in the liver (primary BA) starting from cholesterol. In small intestine, BA act as strong detergents for emulsification, solubilization and absorption of dietary fat, cholesterol, lipid-soluble vitamins. Primary escaping active ileal re-absorption undergo microbiota-dependent biotransformation to secondary colon, passive diffusion into portal vein towards liver. also signaling able play a systemic role variety metabolic functions, mainly through activation nuclear membrane-associated receptors gallbladder, homeostasis is tightly controlled by complex interplay with receptor farnesoid X (FXR), enterokine hormone fibroblast growth factor 15 (FGF15) or human ortholog FGF19 (FGF19). Circulating FGFR4/β-Klotho causes smooth muscle relaxation refilling gallbladder. binding activates FXR-small heterodimer partner (SHP) pathway. This step suppresses unnecessary synthesis promotes continuous enterohepatic circulation BAs. Besides homeostasis, BA-FXR-FGF19 axis governs several processes, hepatic protein, glycogen synthesis, without inducing lipogenesis. These pathways can be disrupted cholestasis, nonalcoholic fatty disease, hepatocellular carcinoma. Thus, targeting FXR activity represent novel therapeutic approach prevention treatment diseases.

Язык: Английский

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Contribution of the microbiome for better phenotyping of people living with obesity

Reviews in Endocrine and Metabolic Disorders, Год журнала: 2023, Номер 24(5), С. 839 - 870

Опубликована: Апрель 29, 2023

Obesity has reached epidemic proportion worldwide and in all ages. Available evidence points to a multifactorial pathogenesis involving gene predisposition environmental factors. Gut microbiota plays critical role as major interface between external factors, i.e., diet, lifestyle, toxic chemicals, internal mechanisms regulating energy metabolic homeostasis, fat production storage. A shift composition is linked with overweight obesity, pathogenic bacterial products metabolites (mainly endocannabinoid-related mediators, short-chain fatty acids, bile catabolites of tryptophan, lipopolysaccharides) subsequent alterations gut barrier, altered insulin resistance chronic, low-grade inflammation. Although animal studies point the links an "obesogenic" development different obesity phenotypes, translational value these results humans still limited by heterogeneity among studies, high variation over time lack robust longitudinal adequately considering inter-individual confounders. Nevertheless, available underscores existence several genera predisposing or, conversely, lean metabolically health phenotype (e.g., Akkermansia muciniphila, species from Faecalibacterium, Alistipes, Roseburia). Further using metagenomics, transcriptomics, proteomics, metabolomics exact characterization confounders are needed this field. Results must confirm that distinct specific microbial-derived represent effective precision interventions against long-term.

Язык: Английский

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Unraveling the Role of the Human Gut Microbiome in Health and Diseases

Microorganisms, Год журнала: 2024, Номер 12(11), С. 2333 - 2333

Опубликована: Ноя. 15, 2024

The human gut is a complex ecosystem that supports billions of living species, including bacteria, viruses, archaea, phages, fungi, and unicellular eukaryotes. Bacteria give genes enzymes for microbial host-produced compounds, establishing symbiotic link between the external environment host at both systemic levels. microbiome, which primarily made up commensal critical maintaining healthy host's immune system, aiding digestion, synthesizing essential nutrients, protecting against pathogenic as well influencing endocrine, neural, humoral, immunological functions metabolic pathways. Qualitative, quantitative, and/or topographic shifts can alter resulting in dysbiosis dysfunction, contribute to variety noncommunicable illnesses, hypertension, cardiovascular disease, obesity, diabetes, inflammatory bowel cancer, irritable syndrome. While most evidence date observational does not establish direct causation, ongoing clinical trials advanced genomic techniques are steadily enhancing our understanding these intricate interactions. This review will explore key aspects relationship microbiota, eubiosis, health highlighting emerging strategies microbiome engineering potential therapeutic approaches various conditions.

Язык: Английский

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Litchi-Derived Polyphenol Alleviates Liver Steatosis and Gut Dysbiosis in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Double-Blinded, Placebo-Controlled Study

Nutrients, Год журнала: 2022, Номер 14(14), С. 2921 - 2921

Опубликована: Июль 16, 2022

Preclinical data suggest the role of litchi extract in alleviating non-alcoholic fatty liver disease (NAFLD) by modulating gut microbiota. We aimed at investigating whether oligonol, a litchi-derived polyphenol, could improve steatosis and dysbiosis patients with NAFLD. Adults grade ≥2 steatosis, defined an MRI proton density fat fraction (MRI-PDFF) ≥11%, were randomly assigned to receive either oligonol or placebo for 24 weeks. The alteration MRI-PDFF microbiota composition assessed 16S ribosomal RNA sequencing examined. There 38 enrolled (n = 19 each group). A significant reduction between week 0 was observed group, while there non-significant decrease group. improvement alpha-diversity demonstrated both groups. oligonol-induced changes characterized reduced abundance pathogenic bacteria, including Dorea, Romboutsia, Erysipelotrichaceae UCG-003 Agathobacter, as well increased short-chain acids (SCFAs)-producing such Akkermansia, Lachnospira, Dialister Faecalibacterium. In summary, this study is first provide evidence that supports improves through modulation bacterial composition. Our results also support beneficial complementary treating

Язык: Английский

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