Western diets and chronic diseases

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(8), P. 2133 - 2147

Published: July 31, 2024

Language: Английский

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Current Therapeutic Landscape for Metabolic Dysfunction-Associated Steatohepatitis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1778 - 1778

Published: Feb. 19, 2025

In recent years, “metabolic dysfunction-associated steatotic liver disease” (MASLD) has been proposed to better connect disease metabolic dysfunction, which is the most common chronic worldwide. MASLD affects more than 30% of individuals globally, and it diagnosed by combination hepatic steatosis obesity, type 2 diabetes, or two risk factors. begins with buildup extra fat, often greater 5%, within liver, causing hepatocytes become stressed. This can proceed a severe form, steatohepatitis (MASH), in 20–30% people, where inflammation causes tissue fibrosis, limits blood flow over time. As fibrosis worsens, MASH may lead cirrhosis, failure, even cancer. While pathophysiology not fully known, current “multiple-hits” concept proposes that dietary lifestyle factors, genetic epigenetic factors contribute elevated oxidative stress inflammation, fibrosis. review article provides an overview pathogenesis evaluates existing therapies as well pharmacological drugs are currently being studied clinical trials for MASH.

Language: Английский

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Vitamin D and Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD): An Update

Nutrients, Journal Year: 2020, Volume and Issue: 12(11), P. 3302 - 3302

Published: Oct. 28, 2020

Non-alcoholic fatty liver disease (NAFLD) is the first cause of chronic worldwide; it ranges from simple steatosis to steatohepatitis (NASH) and, potentially, cirrhosis and hepatocarcinoma. NAFLD also an independent risk factor for type 2 diabetes, cardiovascular diseases, mortality. As largely associated with insulin resistance related disorders, has been recently re-named as Metabolic dysfunction-Associated Fatty Liver Disease (MAFLD). At present, there are no approved pharmacological treatments this condition. Vitamin D a molecule extensive anti-fibrotic, anti-inflammatory, insulin-sensitizing properties, which have proven in hepatic cells involved immune-metabolic pathways within gut-adipose tissue-liver axis. Epidemiological data support relationship hypovitaminosis presence (NASH); however, results vitamin supplementation trials on outcomes controversial. This narrative review provides overview latest evidence pathophysiological connecting NAFLD, emphasis effects treatment MAFLD by nonsystematic literature PubMed published clinical trials. article conforms Scale Assessment Narrative Review Articles (SANRA) guidelines. Evidence so far available supports hypothesis potential benefits selected populations patients, those shorter duration mild moderate damage.

Language: Английский

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Hepatic Krüppel-like factor 16 (KLF16) targets PPARα to improve steatohepatitis and insulin resistance

Gut, Journal Year: 2020, Volume and Issue: 70(11), P. 2183 - 2195

Published: Nov. 30, 2020

Objective Impaired hepatic fatty acids oxidation results in lipid accumulation and redox imbalance, promoting the development of liver diseases insulin resistance. However, underlying pathogenic mechanism is poorly understood. Krüppel-like factor 16 (KLF16) a transcription that abounds liver. We explored whether by what mechanisms KLF16 affects catabolism to improve hepatosteatosis Design expression was determined patients with non-alcoholic disease (NAFLD) mice models. The role regulation metabolism investigated using hepatocyte-specific KLF16-deficient fed high-fat diet (HFD) or an adenovirus/adeno-associated virus alter mouse primary hepatocytes (MPHs) vivo livers. RNA-seq, luciferase reporter gene assay ChIP analysis served explore molecular involved. Results decreased NAFLD, models oleic acid palmitic (OA PA) cochallenged hepatocytes. Hepatic knockout impaired oxidation, aggravated mitochondrial stress, ROS burden, advancing steatosis Conversely, overexpression reduced deposition improved resistance via directly binding promoter peroxisome proliferator-activated receptor α (PPARα) accelerate attenuate oxidative stress db/db HFD mice. PPARα deficiency diminished KLF16-evoked protective effects against MPHs. Hepatic-specific effectively rescued deficiency-induced steatosis, altered balance Conclusions These findings prove direct KLF16–PPARα pathway closely links homeostasis balance, whose dysfunction promotes steatosis.

Language: Английский

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Green Tea and Epigallocatechin Gallate (EGCG) for the Management of Nonalcoholic Fatty Liver Diseases (NAFLD): Insights into the Role of Oxidative Stress and Antioxidant Mechanism

Antioxidants, Journal Year: 2021, Volume and Issue: 10(7), P. 1076 - 1076

Published: July 5, 2021

Nonalcoholic fatty liver diseases (NAFLD) represent a set of disorders progressing from steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma, which induce huge burden human health. Many pathophysiological factors are considered influence NAFLD in parallel pattern, involving insulin resistance, oxidative stress, lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum inflammatory cascades, fibrogenic reaction, etc. However, the underlying mechanisms, including those that development, have not been fully understood. Specifically, mainly mediated by excessive accumulation reactive oxygen species, has participated multiple NAFLD-related signaling serving as an accelerator. Ameliorating stress maintaining redox homeostasis may be promising approach for management NAFLD. Green tea is one most important dietary resources natural antioxidants, above epigallocatechin gallate (EGCG) notably contributes its antioxidative action. Accumulative evidence randomized clinical trials, systematic reviews, meta-analysis revealed beneficial functions green EGCG preventing managing NAFLD, with acceptable safety patients. Abundant animal cellular studies demonstrated protect against initiation development alleviating related metabolism inflammation, tumorigenesis. The targeted pathways include, but limited to, NRF2, AMPK, SIRT1, NF-κB, TLR4/MYD88, TGF-β/SMAD, PI3K/Akt/FoxO1, In this review, we thoroughly discuss stress-related mechanisms involved well summarize protective effects

Language: Английский

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Unraveling the Role of Leptin in Liver Function and Its Relationship with Liver Diseases

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(24), P. 9368 - 9368

Published: Dec. 9, 2020

Since its discovery twenty-five years ago, the fat-derived hormone leptin has provided a revolutionary framework for studying physiological role of adipose tissue as an endocrine organ. Leptin exerts pleiotropic effects on many metabolic pathways and is tightly connected with liver, major player in systemic metabolism. As consequence, understanding hormonal interplay between liver could provide us new therapeutic targets some chronic diseases, increasing problem worldwide. In this review, we assess relevant literature regarding main by direct regulation or through central nervous system (CNS). We draw special attention to contribution non-alcoholic fatty disease (NAFLD) pathogenesis progression more advanced stages steatohepatitis (NASH). Likewise, describe regeneration process after partial hepatectomy, mainstay treatment certain hepatic malignant tumors.

Language: Английский

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Insights into Nonalcoholic Fatty-Liver Disease Heterogeneity

Seminars in Liver Disease, Journal Year: 2021, Volume and Issue: 41(04), P. 421 - 434

Published: July 7, 2021

The acronym nonalcoholic fatty-liver disease (NAFLD) groups a heterogeneous patient population. Although in many patients the primary driver is metabolic dysfunction, complex and dynamic interaction of different factors (i.e., sex, presence one or more genetic variants, coexistence comorbidities, diverse microbiota composition, various degrees alcohol consumption among others) takes place to determine subphenotypes with distinct natural history prognosis and, eventually, response therapy. This review aims address this topic through analysis existing data on differential contribution known pathogenesis clinical expression NAFLD, thus determining observed practice. To improve our understanding NAFLD heterogeneity dominant drivers subgroups would predictably impact development precision-targeted therapies for NAFLD.

Language: Английский

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Role of Leptin in Non-Alcoholic Fatty Liver Disease

Biomedicines, Journal Year: 2021, Volume and Issue: 9(7), P. 762 - 762

Published: June 30, 2021

Non-alcoholic fatty liver disease (NAFLD), which affects about a quarter of the global population, poses substantial health and economic burden in all countries, yet there is no approved pharmacotherapy to treat this entity, nor well-established strategies for its diagnosis. Its prevalence has been rapidly driven by increased physical inactivity, addition excessive calorie intake compared energy expenditure, affecting both adults children. The increase number cases, together with higher morbimortality that entails respect general makes NAFLD serious public problem. Closely related development disease, hormone derived from adipocytes, leptin, involved homeostasis lipid metabolism. Numerous studies have verified relationship between persistent hyperleptinemia steatosis, fibrinogenesis carcinogenesis. Therefore, further role leptin spectrum could represent an advance management set diseases.

Language: Английский

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Hepatic sexual dimorphism — implications for non-alcoholic fatty liver disease

Nature Reviews Endocrinology, Journal Year: 2021, Volume and Issue: 17(11), P. 662 - 670

Published: Aug. 20, 2021

Language: Английский

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The Role of Lipid Sensing Nuclear Receptors (PPARs and LXR) and Metabolic Lipases in Obesity, Diabetes and NAFLD

Genes, Journal Year: 2021, Volume and Issue: 12(5), P. 645 - 645

Published: April 26, 2021

Obesity and type 2 diabetes mellitus (T2DM) are metabolic disorders characterized by inflexibility with multiple pathological organ manifestations, including non-alcoholic fatty liver disease (NAFLD). Nuclear receptors ligand-dependent transcription factors a multifaceted role in controlling many activities, such as regulation of genes involved lipid glucose metabolism modulation inflammatory genes. The activity nuclear is key maintaining flexibility. Their depends on the availability endogenous ligands, like acids or oxysterols, their derivatives produced catabolic action lipases, most which under control receptors. For example, adipose triglyceride lipase (ATGL) activated peroxisome proliferator-activated receptor γ (PPARγ) conversely releases ligands for PPARα, therefore, demonstrating interdependency lipases. diverse biological functions importance syndrome NAFLD has led to substantial effort target them therapeutically. This review summarizes recent findings roles lipases selected receptors, PPARs, X (LXR) obesity, diabetes, NAFLD.

Language: Английский

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